Eur. J. Org. Chem. · © WILEY-VCH Verlag GmbH, D-69451 Weinheim · ISSN 1434–193X

SUPPORTING INFORMATION

Title: Palladium-Catalyzed Bicyclization of 2-Bromo-1,6-dienes and -1,6-enynes to 5-

Membered-Ring-Annelated Vinylcyclopropane Derivatives

Author(s): A. G. Steinig, A. de Meijere*

Received: September 7, 1998

Ref. No.: O98406D

2

Electronic Supporting Information

Palladium-Catalyzed Bicyclization of 2-Bromo-1,6-dienes and -1,6-Eneynes

to 5-Ring-Annelated Vinylcyclopropane DerivativesP

Arno G. Steinig, Armin de Meijere*

3

The starting material for the bromodienes 6, 7, 9–11, a (Z)-configurated bromoalkenyl moiety

(see Scheme 1), 2,4-dibromo-(2Z)-buten-1-ol [(Z)-2], was obtained from 2-butyne-1,4-diol (1)

and aqueous 48% HBr according to a procedure by Seebach et al.[6]. This compound (Z)-2

was treated with cesium acetate in acetonitrile[7] to yield (Z)-3 (94–98%) and then with

triphenylphosphane/bromine to give the dibromide (Z)-4 (92–100%). Both crude compounds

could be used in the next step without further purification. The acetate (Z)-6 was obtained by

alkylating dimethyl allylmalonate (5) with (Z)-4 in 86–87% yield. Hydrolysis of the acetate

(potassium carbonate in

OH

30%

XBr

Y 86–87%

5 EE

BrOR

1 (Z)-2: X = OH, Y = Br

OH

EE

BrOCO2Et

EE

BrOCOCF3

E

E

EE

BrOAc

E

EA

D

(Z)-3: X = OH, Y = OAc(Z)-4: X = Br, Y = OAc

B 94–98%

C 92–100%

(Z)-6: R = Ac(Z)-7: R = H

E~100%

FG

~100%H 84%

(Z)-9 (Z)-10 (Z)-11

8

Scheme 1. Preparation of bromodienes with (Z) configuration of the bromoalkenyl moiety. –

A: 48% HBr (aq), 35 °C, 3 d. – B: CsOAc (1.5 equiv.), MeCN, 20 °C, 8 h. – C:

PPh3/Br2, CH2Cl2, 0–20 °C, 1.5 h. – D: NaH, THF, 0–20 °C, 1 h. – E: K2CO3,

MeOH/H2O, 20 °C, 45 min. – F: NaH, 0–20 °C, 1.5 h. – G: ClCO2Et, C5H5N,

CH2Cl2, 0–20 °C, 5 h. – H: (CF3CO)2O, Et2O, 0–20 °C, 30 min. – E = CO2Me.

4

methanol/water) gave quantitatively the alcohol (Z)-7. The trifluoroacetate (Z)-11 and the

carbonate (Z)-10 were prepared from this alcohol (Z)-7 by reaction with trifluoroacetic

anhydride (84%) and ethyl chloroformate (quant.), respectively. Bromodiene (Z)-9 was

synthesized similarly from dimethyl prenylmalonate (8) and dibromide (Z)-4 (61%).

The preparations of (E)-6 (Schemes 2, 3) started from 2-butyne-1,4-diol (1) as well. After

palladium-catalyzed hydrostannylation (95%) and silylation of the 4-hydroxy group to give the

known vinylstannane 13[8] exclusively with (E)-configuration of the double bond, the tin was

exchanged for bromine and the hydroxy group converted to the

OHX

OH

E

E EE

Br

OTBDMS

EE

Br

OAc

12

5

(E)-6(E)-17

41%

OHX

OTBDMS

OMsBr

OTBDMS

75 80%

~100%

OTBDMSX

OTBDMS

+ + 12

13 1459%

16

A

BX = SnBu3 X = SnBu3

(7%)(63%)

X = SnBu3

15 X = BrC

D

E

F

~100%

Scheme 2. Synthesis of compound (E)-6 via trialkylsilyl-protected intermediates. – A:

TBDMSCl, ImH, DMF, 0 °C, 6 h; 20 °C, 12 h. – B: nBu4NF, THF. – C: Br2,

CCl4, –20 → 20 °C. – D: MsCl, NEt3, CH2Cl2, –60 → 0 °C. – E: NaH, THF, 0

→ 20 °C, 2 h. – F: 1) nBu4NF, 20 °C, 20 min; Ac2O, DMAP (cat.), THF, 20 °C,

50 min. – E = CO2Me.

5

mesylate. Contrary to the stannane, bromoalcohol (E)-15 was configurationally unstable: after

2 days at +2 °C, it had isomerized to a 1:1 mixture of (E)- and (Z)-isomers. Unfortunately, the

order of tin-bromine exchange and mesylation could not be reversed, because on attempted

mesylation of the stannane 13, elimination to 1-tert-butyldimethylsilyloxy-2,3-butadiene took

place. The mesylate (E)-16 was directly used to alkylate dimethyl allylmalonate, and the

product was subsequently converted to the desired acetate (E)-6 in the same pot by treatment

with TBAF and acylation with acetic anhydride (Scheme 2). Alternatively, vinylstannane 12

(isolated product or the reaction mixture from the hydrostannylation) was reacted with acetic

anhydride to give 4-acetate 18 (39–54%), 1-acetate 19 (9–21%), diacetate 20 (13–18%) (the

latter could be hydrolyzed quantitatively to the diol 12 with K2CO3/MeOH/H2O) and up to

10% of starting material. Both monoacetates, which were easily separated by column

chromatography, undergo slow intramolecular transesterification. Tin-bromine exchange

yielded vinyl bromide (E)-3. Upon reaction with triphenylphosphane/bromine, the double bond

isomerized, and thus by alkylation of dimethyl allylmalonate with this dibromide a 1.3:1

mixture of (E)- and (Z)-6 was obtained (Scheme 3).

OHSnBu3

OAc

OAcSnBu3

OH

+

C

81%

5 EE

Br

OAc

82%

52%

12(or reaction mixture of hydrostannylation of 1)

OAcSnBu3

OAc

+ + 12

(E)-3 4

(E,Z)-6

18 (39–54%) 19 (9–21%) 20 (13–18%)

A

0–10%

DE

B

, F

(E/Z ) = 1.3:1

6

Scheme 3. Synthesis of compound (E)-6 via acetates. – A: Ac2O, NEt3, DMAP (cat.),

CH2Cl2, 0–20 °C, 2 h. – B: K2CO3, MeOH/H2O. – C: 20 °C, 1 d. – D: Br2,

CCl4, –10 °C, 30 min. – E: PPh3/Br2, CH2Cl2, 0 → 20 °C, 1 h. – F: NaH, THF,

0 → 20 °C, 1 h. – E = CO2Me.

For comparison, bromodiene 27 with the bromine atom and the acetoxymethyl moiety on the

two different double bonds, was also prepared. As shown in Scheme 4, 2,5-dihydrofuran (21)

was ring-opened with acetyl bromide in the presence of a catalytic amount of zinc[9] to yield 1-

acetoxy-4-bromo-(2E,Z)-butene (22). Dimethyl malonate (24) was then alkylated with 22 and

2,3-dibromo-1-propene (26), respectively, to give the required 27 (E/Z = 7:1).

O

AOAcBr +

OAcBr

5 : 138%

76%

EE

BrOAc

27 (E/Z) = 7 : 1

E

EOAc

86%25 (E/Z) = 7 : 1

21 (E,Z)-22 23

E E

BrBr

2624

CB

Scheme 4. Preparation of bromodiene 27. – A: MeCOBr, C6H6, 0 → 20 °C, 15 h. – B:

NaH, THF, 0 → 20 °C, 2 h. – C: NaH, THF, 0 → 20 °C, 4 h. – E = CO2Me.

Substrate 57 was readily prpared by deprotonating THP-protected propargyl alcohol[22] with

nBuLi, hydroxymethylating with paraformaldehyde, quenching of the alkoxide with methyl

chloroformate, transforming the OTHP to a bromide group by treatment with PPh3/Br2, and

finally alkylating dimethyl allylmalonate (5) with this 1,4-difunctional 2-butyne derivative. This

route to 57 could be shortened considerably by reacting terminally deprotonated propargyl

chloride (55) (Scheme 12) with paraformaldehyde at low temperatures according to a

procedure described by Brandsma,[23a] quenching of the resulting alkoxide with methyl

chloroformate and using this 4-functionalized but-2-yne-1-yl chloride for the alkylation of

dimethyl allylmalonate. The enyne acetate 42 was synthesized by the same sequence, except for

7

using acetyl chloride instead of methyl chloroformate in the acylation step. Simple distillation

under reduced pressure afforded the 2-butyne derivatives 56 and 58 (47 and 48% yield,

respectively [23b]) of sufficient purity for preparative work.

OE

EE

E

E

57

Cl

OE

Cl

565547% 78%

OAc

EE

42

Cl

OAc58

5

48% 76%

5A

B

C

B

Scheme 12. Preparation of enyne carbonate 57 and enyne acetate 42. – A: 1) nBuLi; 2)

(HCHO)n; 3) ClCO2Me, Et2O/hexane. – B: NaH, DMF, 25 °C, 24 h. – C: 1)

nBuLi; 2) (HCHO)n; 3) AcCl, Et2O/hexane. – E = CO2Me.

The corresponding bromide 60 was also prepared (in 85% yield) by alkylation of dimethyl

allylmalonate (5) with 1,4-dibromo-2-butyne (59) (3 equiv. in order to suppress twofold

reaction with the malonate, the excess of 59 can almost completely be recovered), and the

formate 61 was obtained by displacement of bromine in 60 with sodium formate in the

presence of nBu4NBr (34% yield) (Scheme 13). It proved impossible to convert the

propargylic bromide 60 to the bromoallene 62 by refluxing with 1.0 equiv. each of CuBr and

LiBr in THF, as described for 3-bromopropyne itself[24] and secondary or tertiary propargyl

bromides.[25]

8

Br

EE

Br

E

E

85% 6059

5

EE

Br

62

34%

EE

61

OCHO

BrA

CB

Scheme 13. Preparation of enyne formate 61 and bromide 60. – A: NaH, THF, 20 °C, 3 h. –

B: NaO2CH, (nBu)4NBr, 100 °C, 9 h. – C: CuBr, LiBr, THF, 70 °C, 5 h. – E =

CO2Me.

General Procedures

General Procedure for Conversion of Alcohols or their THP ethers to the corresponding

Bromides with Triphenylphosphane/Bromine (GP 1):[37] Bromine (0.61 mL, 1.89 g,

11.8 mmol) is added dropwise to a solution of triphenylphosphane (3.15 g, 12.0 mmol) in

anhydrous CH2Cl2 (40 mL), cooled to 0 °C. During the addition a colorless solid precipitates

(in the case of more diluted solutions there may be no precipitate). If an excess of bromine has

been added (yellow color) triphenylphosphane is added slowly until decolorization. After

stirring for 10 min one adds a solution of the alcohol or its THP ether (11.0 mmol) in

anhydrous CH2Cl2 (5 mL) at 0 °C (the precipitate dissolves), the mixture is brought to room

temp. and stirred for 1 h. Then sat. NaHCO3 solution (40 mL, gas evolution!) is added,

followed by such an amount of hexane that the organic phase is lighter than the aqueous and

that the phases separate well. The organic phase is dried over MgSO4, the solvents are

evaporated. To the residue is added pentane, the precipitate of triphenylphosphanoxide is

filtered off and washed thoroughly with pentane; it may be necessary to filter the filtrate again.

9

After evaporation of the pentane the crude product is purified by column chromatography

and/or distillation.

On a small scale, when dosage of bromine by volume becomes too inexact, bromine is weighed

into a vial with 1–2 mL of anhydrous CH2Cl2, and this solution is used.

General Procedure for Alkylation of Malonates with Allylic and Propargylic Halides

(GP 2):[38] The malonate (10.0 mmol) is added at room temp. dropwise to a suspension of

sodium hydride (10.1 mmol, oil suspension) in anhydrous THF (30 mL). When gas evolution is

finished, the clear solution is cooled to 0–5 °C, 10.1 mmol allyl or propargyl halide are added

(a colorless solid precipitates), and the mixture is warmed to room temp. and stirred for the

given time (60 min are sufficient for primary allylic bromides, primary propargylic chlorides

usually require about 24 h). Most of the THF is removed on a rotovap, the residue is taken up

in sat. NH4Cl or NaHCO3 solution (15 mL), water (15 mL) and ether (20 mL), and the

aqueous phase is extracted with ether (2 × 20 mL). The combined organic phases are washed

with water (20 mL) and sat. NaCl solution (20 mL) and dried over MgSO4. The crude product

is purified by column chromatography on silica gel and/or distillation.

General Procedure for Hydrolysis of Acetates (GP 3): A solution of acetate (9.0 mmol) and

K2CO3 (1.62 g, 11.7 mmol, 1.3 equiv. per acetate) in methanol (35 mL) and H2O (10 mL) is

stirred at room temp. until hydrolysis is complete (for primary allylic acetates about 45 min).

The solvents are removed at room temp., sat. NH4Cl solution (25 mL) is added and the

mixture is extracted with Et2O (4 × 20 mL). The combined organic phases are washed with

sat. NaCl solution (30 mL), dried over Na2SO4, and the crude product is purified by column

chromatography and/or kugelrohr distillation.

If the reaction mixture is not homogeneous, it can be diluted with more MeOH/H2O or pure

methanol.

General Procedure for Tin-Bromine Exchange (GP 5): According to a procedure by Seebach

et al.[6] a solution of bromine (0.8 mmol) in CCl4 (2 mL) is added dropwise to a solution of

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vinylstannane (0.8 mmol) in CCl4 (10 mL) cooled to –15 °C. The cooling bath is removed, and

the mixture is stirred at room temp. for 30 min. CCl4 is then removed at room temp. and the

residue is chromatographed on silica gel (20 g). Because of severe tailing of certain tin

compounds repeated column chromatography may be necessary.

Preparation of Bromodienes

4-Acetoxy-2-bromo-(2Z)-buten-1-ol [(Z)-3]: To a suspension of CsOAc (3.455 g, 18.0 mmol)

in acetonitrile (25 mL) was added at room temp. 2,4-dibromo-(2Z)-buten-1-ol [(Z)-2][6]

(2.759 g, 12.0 mmol). The starting material was completely consumed after stirring for 7 h at

room temp. according to TLC [2: Rf (PE/ether 3:1) = 0.20, 3: Rf (PE/ether 3:1) = 0.06]. The

solvent was evaporated, the residue was dissolved in H2O and Et2O (20 mL each), and the

aqueous phase was extracted with Et2O (2 × 20 mL). The combined organic phases were

washed with sat. NaCl (30 mL) and dried over Na2SO4. The crude product (2.455 g, 98%)

could be used in the next step without further purification. – IR (film): ν = 3405 cm–1 (O–H),

2936, 1740 (C=O), 1669 (C=C), 1437 (CH2 and CH3 deformation), 1381, 1246 (C–O), 1092,

1026, 972, 794, 691, 608. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 2.08 (s, 3 H, COCH3),

2.15–2.40 (br s, 1 H, OH), 4.27 (app q, 4J = 5J = 1.2 Hz, 2 H, 1-H), 4.73 (dt, 3J = 6.0,

5J = 1.2 Hz, 2 H, 4-H), 6.24 (tt, 3J = 6.0, 4J = 1.4 Hz, 1 H, 3-H). – 13C NMR (62.9 MHz,

CDCl3, DEPT135): δ = 20.75 (+, COCH3), 63.31 (–, C-4), 67.52 (–, C-1), 123.49 (+, C-3),

129.54 (Cquat, C-2), 170.93 (Cquat, COCH3). – MS (EI, 70 eV), m/z (%): 192/190 (23/23)

[M+ – H2O], 150/148 (9/9) [M+ – HOAc], 129 (11) [M+ – Br], 111 (2) [M+ – Br – H2O], 87

(15) [M+ – Br – O=C=CH2], 69 (8) [M+ – Br – HOAc], 43 (100) [MeCO+]. – MS (DCI,

NH3), m/z (%): 245/243 (2/2) [M + NH4+ + NH3], 228/226 (100/100) [M + NH4

+]. –

C6H9BrO3 (209.0): calc. C 34.48, H 4.34; found C 34.75, H 4.36.

4-Acetoxy-1,2-dibromo-(2Z)-butene [(Z)-4]: Following GP 1, 4-acetoxy-2-bromo-(2Z)-buten-

1-ol [(Z)-3] (2.455 g, 11.7 mmol) was reacted with PPh3 (3.410 g, 13.0 mmol) and bromine

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(0.66 mL, 2.046 g, 12.8 mmol) in 48 mL of CH2Cl2 yielding 3.184 g (100%) of dibromide

[(Z)-4], which could be used directly for the malonate alkylation. Purification was achieved by

chromatography on silica gel [60 g, column 2.9 × 21 cm, PE/ether 20:1, Rf (PE/ether

20:1) = 0.20] and kugelrohr distillation at 0.005 Torr and 60 °C. Repeated experiments on

different scales gave yields of 92–100%. – IR (film): ν = 3026 cm–1, 2962, 1742 (C=O), 1652

(C=C), 1436 (CH2 and CH3 deformation), 1378, 1230 (C–O), 1100, 1032, 971, 908, 629,

605, 567, 542. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 2.09 (s, 3 H, COCH3), 4.23 (q,

4J = 5J = 0.9 Hz, 2 H, 1-H), 4.70 (dt, 3J = 5.9, 5J = 0.9 Hz, 2 H, 4-H), 6.32 (tt, 3J =5.9,

4J = 0.9 Hz, 1 H, 3-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 20.68 (+, COCH3),

37.13 (–, C-1), 63.56 (–, C-4), 124.65 (Cquat, C-2), 128.55 (+, C-3), 170.49 (Cquat, COCH3).

– MS (EI, 70 eV), m/z (%): 275/273/271 (0.02/0.03/0.02) [M+ + H], 215/213/211 (1/3/1) [M+

– OAc], 194/192 (3/3), 193/191 (48/50) [M+ – Br], 151/149 (5/5) [M+ – Br – O=C=CH2],

134/132 (2/2) [M+ – Br – OAc], 133/131 (6/6) [M+ – Br – HOAc], 53 (7) [M+ – 2 Br –

OAc], 43 (100) [MeCO+]. – C6H8Br2O2 (271.9): calc. C 26.50, H 2.97; found C 26.58,

H 2.88.

Dimethyl [4'-Acetoxy-2'-brom-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-6]: According to

GP 2, dimethyl allylmalonate (5) (1.96 g, 11.4 mmol) was reacted with NaH (468 mg,

11.7 mmol, 60% oil suspension) and 4-acetoxy-1,2-dibromo-(2Z)-butene [(Z)-4] (3.07 g,

11.3 mmol) in THF (30 mL) for 1 h. The crude product was purified by chromatography on

80 g of silica gel (column 2.9 × 28 cm, PE/ether 4:1, changed to 2:1 when 6 is eluting) yielding

3.58 g (87%) of (Z)-6 as a colorless oil that crystallized after about 1 week at +2 °C, colorless

solid, mp. 34–35 °C, Rf (PE/ether 4:1) = 0.14. – IR (non-solidified melt): ν = 3079 cm–1

[C(sp2)–H], 2953, 2843 [C(sp3)–H], 1737 (C=O), 1642 (C=C), 1437 (CH3 deformation),

1379, 1363, 1329, 1222 (C–O), 1127, 1031, 996, 967, 929 (CH=CH2), 855, 819, 651, 603,

577. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.07 (s, 3 H, OCOCH3), 2.73 (dt, 3J = 7.3,

4J = 1.1 Hz, 2 H, 1''-H), 3.18 (d, 4J = 0.6 Hz, 2 H, 1'-H), 3.73 [s, 6 H, CO2CH3; 13C satellite:

d, 1J(C,H) = 147.8 Hz], 4.65 (d, 3J = 5.9 Hz, 2 H, 4'-H), 5.07–5.16 (m, 2 H, 3''-H), 5.73 (ddt,

3J = 17.7, 3J = 9.4, 3J = 7.3 Hz, 1 H, 2''-H), 5.99 (t, 3J = 5.9 Hz, 1 H, 3'-H). – 13C NMR

12

(62.9 MHz, CDCl3, DEPT135): δ = 20.74 (+, OCOCH3), 36.21 (–, C-1''), 43.23 (–, C-1'),

52.64 (+, CO2CH3), 57.11 (Cquat, C-2), 63.72 (–, C-4'), 119.72 (–, C-3''), 123.78 (Cquat, C-

2'), 129.08 (+, C-2''*), 131.94 (+, C-3'*), 170.44 (Cquat, CO2CH3), 170.62 (Cquat, OCOCH3).

– MS (EI, 70 eV), m/z (%): 283 (100) [M+ – Br], 223 (3) [M+ – Br – HOAc], 209 (23) [M+ –

Br – MeCO – OMe], 177 (9) [M+ – Br – MeCO – MeOH – OMe], 163 (19) [M+ – Br –

HOAc – MeOH – CO], 149 (11) [M+ – Br – MeCO – MeOH – OMe – CO], 135 (4) [M+ –

Br – HOAc – MeOH – 2 CO], 121 (3) [M+ – Br – MeCO – MeOH – OMe – 2 CO], 108

(12), 103 (6), 43 (42) [MeCO+]. – C14H19BrO6 (363.2): calc. C 46.30, H 5.27, Br 22.00;

found C 46.37, H 5.15, Br 22.01.

Dimethyl [2'-Bromo-4'-hydroxy-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-7]: According to

GP 3, dimethyl [4'-acetoxy-2'-bromo-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-6] (3.26 g,

8.98 mmol) was reacted with K2CO3 (1.62 g, 11.7 mmol) in methanol (35 mL) and H2O

(10 mL) at room temp. for 45 min. The crude product was purified by flash chromatography

on silica gel (30 g, column 2.2 × 16 cm, PE/ether 3:2) yielding 2.866 g (100%) of (Z)-7 as a

colorless oil, Rf (PE/ether 1:1) = 0.29. – IR (film): ν = 3420 cm–1 (O–H), 3080 [C(sp2)–H],

2954 [C(sp3)–H], 1734 (C=O), 1653 (C=C), 1437 (CH3 deformation), 1296, 1218 (C–O),

1091, 1020, 928 (CH=CH2), 856, 604. – 1H NMR (250 MHz, CDCl3, TMS): δ = 1.61 (br s, t

not completely resolved, 1 H, OH), 2.74 (dt, 3J = 7.4, 4J = 1.1 Hz, 2 H, 1''-H), 3.18 (d,

4J = 0.7 Hz, 2 H, 1'-H), 3.73 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.25

(br d, 3J = 5.5 Hz, 2 H, 4'-H), 5.08–5.18 (m, 2 H, 3''-H), 5.66 (ddt, 3J = 17.4, 3J = 9.7,

3J = 7.3 Hz, 1 H, 2''-H), 6.05 (t, 3J = 5.8 Hz, 1 H, 3'-H). – 13C NMR (62.9 MHz, CDCl3,

DEPT135): δ = 36.19 (–, C-1''), 43.19 (–, C-1'), 52.63 (+, CO2CH3), 57.22 (Cquat, C-2),

62.36 (–, C-4'), 119.72 (−, C-3''), 121.52 (Cquat, C-2'), 131.95 (+, C-2''*), 133.78 (+, C-3'*),

170.58 (Cquat, CO2CH3). – MS (EI, 70 eV), m/z (%): 241 (100) [M+ – Br], 163 (8) [M+ – Br

– H2O – MeOH – CO], 159 (4) [M+ – Br – H2O – 2 MeOH], 139 (5), 121 (4) [M+ – Br –

2 MeOH – 2 CO], 108 (9), 103 (4) [M+ – Br – H2O – 2 MeOH – 2 CO], 91 (8), 77 (5), 59

(8), 41 (10). – C12H17BrO5 (321.2): calc. C 44.88, H 5.34; found C 44.74, H 5.27.

13

Dimethyl [4'-Acetoxy-2'-bromo-(2'Z)-butenyl][3''-methyl-(2''E)-butenyl]malonate [(Z)-9]:

According to GP 2, dimethyl [3'-methyl-(2'E)-butenyl]malonate (8)[38] (701 mg, 3.50 mmol)

was reacted with NaH (140 mg, 3.50 mmol, 60% oil suspension) and 4-acetoxy-1,2-dibromo-

(2Z)-butene [(Z)-4] (916 mg, 3.37 mmol) in THF (10 mL) at room temp. for 1.5 h.

Chromatography on silica gel (25 g, column 2.2 × 16 cm, PE/ether 5:1) gave 800 mg (61%) of

(Z)-9 as a colorless oil, Rf (PE/ether 5:1) = 0.14 after distillation in a microsublimation

apparatus at 0.01 Torr and 120 °C bath temp. – IR (film): ν = 2953 cm–1 [C(sp3)–H], 1738

(C=O), 1653 (C=C), 1437 (CH3 deformation), 1379, 1363, 1274, 1224 (C–O), 1177, 1121,

1063, 1030, 964, 902, 862, 818, 788, 606, 580, 553, 451. – 1H NMR (250 MHz, CDCl3,

TMS): δ = 1.60 (d, 4J = 0.9 Hz, 3 H, 3''-CH3), 1.70 (d, 4J = 1.2 Hz, 3 H, 4''-H), 2.07 [s, 3 H,

OCOCH3; 13C satellite: d, 1J(C,H) = 129.7 Hz], 2.68 (br d, 3J = 7.2 Hz, 2 H, 1''-H), 3.18

(br s, 2 H, 1'-H), 3.73 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.7 Hz], 4.65 (d,

3J = 5.9 Hz, 2 H, 4'-H), 4.92 (app tt, 3J = 7.2, 4J = 1.4 Hz, 1 H, 2''-H), 5.92 (t, 3J = 5.9 Hz,

1 H, 3'-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 17.95 (+, 3''-CH3), 20.72 (+,

OCOCH3), 25.98 (+, C-4''), 30.29 (–, C-1''), 43.11 (–, C-1'), 52.58 (+, CO2CH3), 56.99

(Cquat, C-2), 63.75 (–, C-4'), 116.95 (+, C-3'), 123.97 (Cquat, C-2'), 128.67 (+, C-2''), 136.09

(Cquat, C-3''), 170.56 (Cquat, OCOCH3), 170.79 (Cquat, CO2CH3). – MS (EI, 70 eV), m/z

(%): 311 (56) [M+ – Br], 251 (3) [M+ – Br – HOAc], 243 (22), 219 (8) [M+ – Br – CO –

2 MeOH], 199 (34), 198 (58), 191 (19) [M+ – Br – HOAc – MeOH – CO], 183 (55), 167

(60), 166 (100), 151 (24), 138 (52), 135 (57), 131 (20), 123 (10), 107 (10), 91 (12), 79 (20),

69 (76), 59 (21), 43 (64) [MeCO+], 41 (46). – C16H23BrO6 (391.3): calc. C 49.12, H 5.93;

found C 48.76, H 5.75.

Dimethyl [4'-Ethoxycarbonyloxy-2'-bromo-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-10]: To

a solution of dimethyl [2'-bromo-4'-hydroxy-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-7]

(215 mg, 0.669 mmol) and pyridine (73 mL, 71 mg, 0.90 mmol) in anhydrous CH2Cl2 (4 mL)

was added at 0 °C dropwise ethyl chloroformate (86 mL, 98 mg, 0.90 mmol). After stirring for

5 h at room temp., the reaction mixture was worked up by pouring it into a 5% solution of

HCl (10 mL), separating the phases, extracting the aqueous phase with CH2Cl2 (4 × 10 mL),

14

washing the combined organic phases with sat. NaHCO3 sol. (20 mL) and drying them over

MgSO4. The crude product was purified by chromatography an silica gel (10 g, column 1.5 ×

10 cm, PE/ether 5:1), yielding 263 mg (100%) of carbonate (Z)-10 as a colorless oil, Rf

(PE/ether 5:1) = 0.17, (Z/E) = 9:1. – IR (film): ν = 3080 cm–1 [C(sp2)–H], 2984, 2954

[C(sp3)–H], 1741 (C=O), 1642 (C=C), 1437 (CH3 deformation), 1380, 1365, 1258 and 1218

(C–O), 1129, 1000, 927 (CH=CH2), 876, 856, 791, 585. – 1H NMR (250 MHz, CDCl3,

TMS): δ = 1.31 (t, 3J = 7.1 Hz, 3 H, OCO2CH2CH3), 2.72 (dt, 3J = 7.3, 4J = 1.1 Hz, 2 H, 1''-

H), 3.19 (d, 4J = 0.8 Hz, 2 H, 1'-H), 3.73 [s, 6 H, CO2CH3; 13C satellite: d,

1J(C,H) = 147.8 Hz], 4.21 (q, 3J = 7.1 Hz, 2 H, OCO2CH2CH3), 4.71 (d, 3J = 5.8 Hz, 2 H,

4'-H), 5.07–5.16 (m, 2 H, 3''-H), 5.62 (ddt, 3J = 17.6, 3J = 9.5, 3J = 7.3 Hz, 1 H, 2''-H), 6.02

(tt, 3J = 5.8, 4J = 0.8 Hz, 1 H, 3'-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 14.19

(+, OCO2CH2CH3), 36.15 (–, C-1''), 43.18 (–, C-1'), 52.63 (+, CO2CH3), 57.03 (Cquat, C-2),

64.24 (–, C-4'), 66.67 (–, OCO2CH2CH3), 119.73 (–, C-3''), 123.94 (Cquat, C-2'), 128.64 (+,

C-2''*), 131.85 (+, C-3'*), 154.80 (Cquat, OCOCH2CH3), 170.38 (Cquat, CO2CH3). – MS (EI,

70 eV), m/z (%): 313 (100) [M+ – Br], 305/303 (1/1) [M+ – OEt – CO2], 273/271 (2/2) [M+ –

OEt – CO2 – MeOH], 245/243 (2/2) [M+ – OEt – CO2 – MeOH – CO], 223 (3) [M+ – Br –

CO2 – EtOH], 209 (4), 177 (5), 163 (14) [M+ – Br – EtOH – CO2 – MeOH – CO], 149 (8),

139 (3), 121 (2) [M+ – Br – MeCO – MeOH – OMe – 2 CO], 108 (6), 103 (4) [M+ – Br –

EtOH – CO2 – 2 MeOH – 2 CO], 91 (4), 59 (5), 41 (5). – C15H21BrO7 (393.2): calc.

C 45.82, H 5.38; found C 45.85, H 5.37.

Signals of Dimethyl [4'-Ethoxycarbonyloxy-2'-bromo-(2'E)-butenyl]-2''-propenylmalonate [(E)-

10]: 1H NMR (250 MHz, CDCl3, TMS): δ = 2.76 (dt, 3J = 7.3, 4J = 1.1 Hz, 2 H, 1''-H), 3.26

(s, 2 H, 1'-H), 3.73 (s, 6 H, CO2CH3), 4.20 (q, 3J = 7.1 Hz, 2 H, OCO2CH2CH3), 4.57 (d,

3J = 7.3 Hz, 2 H, 4'-H), [signals of 2''-H and 3''-H are hidden under those of the (Z) isomer],

6.23 (t, 3J = 7.3 Hz, 1 H, 3'-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 36.85 (–, C-

1''), 38.04 (–, C-1'), 52.72 (+, CO2CH3), 57.19 (Cquat, C-2), 63.65 (–, C-4'), 124.82 (Cquat, C-

2'), 130.86 (+, C-2''*), 131.99 (+, C-3'*), 170.44 (Cquat, CO2CH3), the other signals coincide

with those of the (Z) isomer.

15

Dimethyl 2'-Propenyl-[4''-trifluoroacetoxy-2''-bromo-(2''Z)-butenyl]malonate [(Z)-11]: To a

solution of dimethyl [2'-bromo-4'-hydroxy-(2'Z)-butenyl]-2''-propenylmalonate [(Z)-7]

(642 mg, 2.00 mmol) and DMAP (10 mg) in anhydrous ether (10 mL) was added

trifluoroacetic anhydride (630 mg, 3.00 mmol) at 0 °C. After stirring at 0 °C for 20 min and at

room temp. for 30 min, the mixture was poured into H2O (8 mL), the organic layer was

washed with sat. NaCl/NaHCO3 sol. (6 mL/2 mL) and dried over MgSO4. The crude product

was purified by kugelrohr distillation at 0.02 Torr and 105 °C oven temp. yielding 705 mg

(84%) of trifluoroacetate (Z)-11 as a colorless oil, Rf (PE/ether 2:1) = 0.51, (Z/E) = 9:1. –

IR (film): ν = 3077 cm–1 [C(sp2)–H], 2956, 2848 [C(sp3)–H], 1790 (CF3C=O), 1737 (C=O),

1644 (C=C), 1438 (CH3 deformation), 1394, 1348, 1221 (C–O, C–F), 1151, 1061, 995, 928

(CH=CH2), 775, 733, 585, 522. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.74 (dt, 3J = 7.3,

4J = 1.2 Hz, 2 H, 1'-H), 3.23 (d, 4J = 0.7 Hz, 2 H, 1''-H), 3.745 [s, 6 H, CO2CH3;

13C satellite: d, 1J(C,H) = 147.8 Hz], 4.93 (d, 3J = 6.1 Hz, 2 H, 4''-H), 5.08–5.18 (m, 2 H, 3'-

H), 5.73 (ddt, 3J = 16.4, 3J = 10.7, 3J = 7.3 Hz, 1 H, 2'-H), 5.99 (tt, 3J = 6.1, 4J = 0.8 Hz,

1 H, 3''-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 36.30 (–, C-1'), 43.25 (–, C-1''),

52.72 (+, CO2CH3), 57.02 (Cquat, C-2), 66.59 (–, C-4''), 114.32 [Cquat, q, 1J(C,F) = 286 Hz,

CF3CO], 119.76 (–, C-3'), 126.20 (+, C-2'*), 126.90 (Cquat, C-2''), 131.70 (+, C-3''*), 157.06

[Cquat, q, 2J(C,F) = 43 Hz, CF3CO], 170.21 (Cquat, CO2CH3). – MS (EI, 70 eV), m/z (%):

418/416 (0.04/0.04) [M+], 387/385 (0.6/0.7) [M+ – OMe], 359/357 (0.05/0.05) [M+ – OMe –

CO], 337 (100) [M+ – Br], 277 (4) [M+ – Br – MeOH – CO], 241 (11), 163 (12) [M+ – Br –

CF3CO2H – MeOH – CO], 149 (11), 139 (9), 105 (6), 103 (7), 91 (6), 59 (10), 41 (7). –

C14H16BrF3O6 (417.2): calc. C 40.31, H 3.87; found C 40.43, H 4.12.

Signals of Dimethyl 2'-Propenyl-[4''-trifluoroacetoxy-2''-bromo-(2''E)-butenyl]malonate [(E)-

11]: 1H NMR (250 MHz, CDCl3, TMS): δ = 2.74 (dt, 3J = 6.1, 4J = 1.2 Hz, 2 H, 1'-H), 3.27

(s, 2 H, 1''-H), 3.754 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.81 (d,

3J = 7.6 Hz, 2 H, 4''-H), [signals of 2'-H and 3'-H are hidden under those of the (Z) isomer],

6.24 (t, 3J = 7.5 Hz, 1 H, 3''-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 37.10 (–, C-

1'), 38.14 (–, C-1''), 52.72 (+, CO2CH3), 57.07 (Cquat, C-2), 63.83 (–, C-4''), 127.10 (Cquat,

16

C-2''), 128.50 (+, C-2'*), 131.81 (+, C-3''*), 170.29 (Cquat, CO2CH3), the other signals

coincide with those of the (Z) isomer.

2-Tributylstannyl-(2E)-butene-1,4-diol (12): 2-Butyne-1,4-diol (1) (172 mg, 2.00 mmol) was

suspended in a solution of Pd(OAc)2 (9 mg, 0.04 mmol, 2 mol%) and PPh3 (31 mg,

0.12 mmol, 6 mol%) in anhydrous CH2Cl2 (6 mL), and tributyltin hydride (0.59 mL, 638 mg,

2.2 mmol) was added dropwise at room temp., during which the diol dissolved completely.

After stirring for 20 min, the crude product was chromatographed on silica gel (8.5 g, column

1.5 × 11 cm, PE/ether 1:1) to yield 734 mg (97%) of vinylstannane 12 as a colorless oil,

Rf (PE/ether 1:1) = 0.33. The spectroscopical data are in accordance with the literature.[41]

This reaction can be scaled up to at least 25 mmol without problems (see preparation of 18).

Control experiment: To a suspension of 2-butyne-1,4-diol (1) (86 mg, 1.0 mmol) in CH2Cl2

(4 mL) was added at room temp. tributyltin hydride (0.30 mL, 325 mg, 1.1 mmol). After

stirring for 2 h at room temp. the diol was still suspended and according to TLC no

vinylstannane 12 was formed. PPh3 (15 mg, 0.057 mmol) was added and stirring was

continued overnight. Vinylstannane 12 could not be detected by TLC, the diol was still

suspended. Upon addition of Pd(OAc)2 (4 mg, 0.02 mmol), the reaction mixture turned brown,

gas was evolved and TLC showed the spot of 12.

4-tert-Butyldimethylsilyloxy-2-tributylstannyl-(2E)-buten-1-ol (13): 2-Tributylstannyl-(2E)-

butene-1,4-diol (12) (2.033 g, 5.39 mmol) was reacted with TBDMSCl (820 mg, 5.44 mmol)

and imidazole (368 mg, 5.40 mmol) in anhydrous DMF (40 mL) according to ref.[8]; the

reaction time, however, was increased to 6 h at 0 °C and 12 h at room temp. After adding ice

(2.5 g) and Et2O (200 mL), the mixture was washed with sat. NH4Cl sol. (3 × 50 mL) and

dried over Na2SO4. Chromatographic separation of the crude mixture on silica gel (50 g,

deactivated with 0.5% NEt3, column 2.2 × 32 cm, PE/ether 5:1, after elution of fraction II

changed to 2:1) gave fraction I: 220 mg of 1,4-bis(tert-butyldimethylsilyloxy)-2-

tributylstannyl-(2E)-butene (14) (7%), colorless oil, Rf (PE/ether 5:1) = 0.83. – 1H NMR

(250 MHz, CDCl3, CHCl3): δ = 0.06 and 0.07 [s, 6 H each, Si(CH3)2], 0.79–1.06 [m, 15 H,

17

Sn(CH2CH2CH2CH3)3], 0.901 and 0.905 [s, 9 H each, SiC(CH3)3], 1.24–1.38 [m, 6 H,

Sn(CH2CH2CH2CH3)3], 1.43–1.55 [m, 6 H, Sn(CH2CH2CH2CH3)3], 4.23 (dt, 3J = 5.4,

5J = 1.2 Hz, 2 H, 4-H), 4.35 (dt, 4J = 2.4, 5J = 1.2 Hz, 2 H, 1-H), 5.59 (tt, 3J = 5.3,

4J = 2.4 Hz, 1 H, 3-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = –5.34 and –5.08 [+,

Si(CH3)2], 10.25 [–, Sn(CH2CH2CH2CH3)3], 13.74 [+, Sn(CH2CH2CH2CH3)3], 18.34 and

18.57 [Cquat, SiC(CH3)3], 25.94 and 26.15 [+, SiC(CH3)3], 27.46 [–,

Sn(CH2CH2CH2CH3)3], 29.24 [–, Sn(CH2CH2CH2CH3)3], 60.95 (–, C-4), 64.60 (–, C-1),

137.21 (+, C-3), 147.85 (Cquat, C-2). – Fraction II: 1.66 g (63%) of 4-tert-butyldimethyl-

silyloxy-2-tributylstannyl-(2E)-buten-1-ol (13), colorless oil, Rf (PE/ether 5:1) = 0.63, known

compound.[6,8] – Fraction III: 247 mg (12% recovery) of diol 12.

Desilylation of 1,4-bis(tert-butyldimethylsilyloxy)-2-tributylstannyl-(2E)-butene (14): A

solution of 14 (220 mg, 0.363 mmol) in anhydrous THF (6 mL) and TBAF (1 M in THF,

0.8 mL, 0.8 mmol) was stirred at room temp. for 1 h. The reaction mixture was diluted with

Et2O (6 mL), filtered over silica gel (10 g, column 1.5 × 11 cm, ether), the solvents were

evaporated and the residue was purified by chromatography on silica gel (15 g, column 1.5 ×

16 cm, PE/ether 1:1) yielding 81 mg (59%) of diol 12.

2-Bromo-4-tert-butyldimethylsilyloxy-(2E)-buten-1-ol (15): A solution of 4-tert-butyl-

dimethylsilyloxy-2-tributylstannyl-(2E)-buten-1-ol (13) (410 mg, 0.834 mmol) in CCl4 (10 mL)

was reacted with a solution of bromine (133 mg, 0.832 mmol) in CCl4 (2 mL), according to

GP 5. Chromatography on flash silica gel (20 g, column 1.5 × 26 cm, PE/ether 6:1, during

elution of 15 changed to 2:1) yielded 186 mg (80%) of 15 as a colorless oil, Rf (PE/ether

4:1) = 0.23. The yields were lower (75%) if the chromatography had to be repeated. – IR

(film): ν = 3374 cm–1 (O–H), 2955, 2929, 2884, 2857, 1646 (C=C), 1472, 1463, 1376, 1362

(CH2 and CH3 deformation), 1258 (SiCH3), 1091 and 1039 (C–O), 939, 837, 813 (C=CH),

778, 668. – 1H NMR (250 MHz, CDCl3, TMS): δ = 0.097 [s, 6 H, Si(CH3)2; 13C satellite: d,

1J(C,H) = 118.4 Hz, 29Si satellite: d, 2J(Si,H) = 6.0 Hz], 0.912 [s, 9 H, SiC(CH3)3;

13C satellite: d, 1J(C,H) = 125.4 Hz, 29Si satellite: d, 3J(Si,H) = 5.8 Hz], 2.77 (t, 3J = 6.6 Hz,

18

1 H, OH; coupling disappears at higher concentrations), 4.23 (dt, 3J = 6.4, 5J = 0.5 Hz, 2 H,

4-H), 4.35 (br d, 3J = 6.4 Hz, 2 H, 1-H), 6.16 (tt, 3J = 6.4, 4J = 0.6 Hz, 1 H, 3-H). –

13C NMR (62.9 MHz, CDCl3, DEPT135): δ = –5.33 [+, Si(CH3)2], 18.21 [Cquat,

SiC(CH3)3], 25.77 [+, SiC(CH3)3], 60.15 (–, C-4), 63.89 (–, C-1), 126.82 (Cquat, C-2),

133.17 (+, C-3).

After storage for 2 d at +2 °C the pure (E) isomer had isomerized to an (E/Z) mixture (ratio

approx. 1:1, chemical shifts from the spectra of the mixture). – (Z) isomer: 1H NMR

(250 MHz, CDCl3, TMS): δ = 0.095 [s, 6 H, Si(CH3)2], 0.905 [s, 9 H, SiC(CH3)3], 2.91 (br s,

1 H, OH), 4.18 (d, 3J = 7.1 Hz, 2 H, 4-H), 4.37 (s, 2 H, 1-H), 6.27 (t, 3J = 7.1 Hz, 1 H, 3-H).

– 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = –3.64 [+, Si(CH3)2], 17.93 [Cquat,

SiC(CH3)3], 25.60 [+, SiC(CH3)3], 58.95 (–, C-4), 63.48 (−, C-1), 128.11 (Cquat, C-2),

133.10 (+, C-3).

2-Bromo-4-tert-butyldimethylsilyloxy-1-methanesulfonyloxy-(2E)-butene (16): To a cooled

solution (acetone/dry ice cooling bath) of 2-bromo-4-tert-butyldimethylsilyloxy-(2E)-buten-1-

ol (15) (186 mg, 0.661 mmol) and triethylamine (0.11 mL, 80 mg, 0.79 mmol) in CH2Cl2

(2 mL) was added dropwise a solution of methanesulfonyl chloride (80 mg, 0.70 mmol) in

CH2Cl2 (1 mL), and the mixture was stirred for 30 min at this temp. and for 1 h at room temp.

The reaction mixture was worked up by washing with H2O and sat. NaCl sol. (3 mL each) and

drying of the organic phase over Na2SO4. After removal of the solvent at room temp. one

obtained 238 mg (100%) of mesylate 16 as a pale yellow oil which was used in the next step

without further purification. – IR (film): ν = 3027 cm–1, 2955, 2930, 2885, 2857, 1647 (C=C),

1472, 1463 (CH2 and CH3 deformation), 1361 (S=O), 1258 (SiCH3), 1177 (S=O), 1093 (C–

O), 1027, 1006, 974, 943, 837, 813 (C=CH), 780, 669, 527 (S–O). – 1H NMR (250 MHz,

CDCl3, TMS): δ = 0.09 [s, 6 H, Si(CH3)2; 29Si satellite: d, 2J(Si,H) = 6.1 Hz], 0.90 [s, 9 H,

SiC(CH3)3; 29Si-satellite: d, 3J(Si,H) = 5.8 Hz], 3.09 (s, 3 H, OSO2CH3), 4.27 (d,

3J = 6.3 Hz, 2 H, 4-H), 5.01 (s, 2 H, 1-H), 6.36 (t, 3J = 6.2 Hz, 1 H, 3-H). – 13C NMR

(62.9 MHz, CDCl3, DEPT135): δ = –5.41 [+, Si(CH3)2], 18.19 [Cquat, SiC(CH3)3], 25.75 [+,

19

SiC(CH3)3], 38.61 (+, OSO2CH3), 60.30 (–, C-4), 68.84 (–, C-1), 117.14 (Cquat, C-2),

139.46 (+, C-3).

Dimethyl [4'-tert-Butyldimethylsilyloxy-2'-bromo-(2'E)-butenyl]-2''-propenylmalonate (17):

According to GP 2 dimethyl allylmalonate (5) (115 mg, 0.67 mmol) was reacted with NaH

(28 mg, 0.70 mmol, 60% oil suspension) and 2-bromo-4-tert-butyldimethylsilyloxy-1-methan-

sulfonyloxy-(2E)-butene (16) (237 mg, 0.659 mmol) in THF (4 mL) at room temp. for 2 h.

After filtration over a short silica gel column (5 g, column 1.5 × 6 cm, PE/ether 6:1) 118 mg

(41%) of 17 was obtained, Rf (PE/ether 4:1) = 0.49. – 1H NMR (250 MHz, CDCl3, TMS): δ

= 0.07 [s, 6 H, Si(CH3)2; 29Si satellite: d, 2J(Si,H) = 6.0 Hz], 0.89 [s, 9 H, SiC(CH3)3;

29Si satellite: d, 3J(Si,H) = 5.8 Hz], 2.75 (d, 3J = 7.3 Hz, 2 H, 1''-H), 3.22 (s, 2 H, 1'-H), 3.73

[s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.13 (d, 3J = 6.6 Hz, 2 H, 4'-H),

5.08–5.16 (m, 2 H, 3''-H), 5.69 (ddt, 3J = 17.7, 3J = 10.1, 3J = 7.3 Hz, 1 H, 2''-H), 6.18 (t,

3J = 6.6 Hz, 1 H, 3'-H).

4-Acetoxy-2-tributylstannyl-(2E)-buten-1-ol (18) and 4-Acetoxy-3-tributylstannyl-(3E)-buten-

1-ol (19); Method A: To a solution of 2-tributylstannyl-(2E)-butene-1,4-diol (12) (328 mg,

0.87 mmol), NEt3 (192 mg, 1.9 mmol) and DMAP (6 mg, 0.05 mmol) in CH2Cl2 (5 mL) was

added at 0 °C acetic anhydride (92 mg, 0.90 mmol). The mixture was then stirred for 1.5 h at

room temp., followed by filtration over silica gel (20 g, column 1.5 × 24 cm, ether) to separate

unreacted diol 12 (80 mg, 24% recovery) from the acetylation products which were then

separated on silica gel (20 g, columnn 1.5 × 24 cm, PE/ether 5:1, after elution of 20 changed

to 2:1). One obtained fraction I: 54 mg (13%) of 1,4-diacetoxy-2-tributylstannyl-(2E)-butene

(20), colorless oil, Rf (PE/ether 1:1) = 0.65, Rf (PE/ether 4:1) = 0.40, incomplete

spectroscopic data in ref.[42]. – IR (film): ν = 2957 cm–1, 2928, 2872, 2854, 1747 (C=O),

1458 (CH2 and CH3 deformation), 1376, 1362, 1225 (C–O), 1030, 963, 875, 777, 667, 602,

507. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 0.79–1.06 [m, 15 H,

Sn(CH2CH2CH2CH3)3], 1.24–1.38 [m, 6 H, Sn(CH2CH2CH2CH3)3], 1.43–1.55 [m, 6 H,

Sn(CH2CH2CH2CH3)3], 2.08 [s, 6 H, COCH3; 13C satellite: d, 1J(C,H) = 129.5 Hz], 4.63 [d,

20

3J = 6.0 Hz, 2 H, 4-H; Sn satellite: d, 4J(Sn,H) = 8.8 Hz], 4.83 [dt, 4J = 2.1, 5J = 1.0 Hz, 2 H,

1-H; Sn satellite: d, 3J(Sn,H) = 33.9 Hz], 5.73 [tt, 3J = 6.0, 4J = 2.1 Hz, 1 H, 3-H;

Sn satellites: 2 d, 3J(119Sn,H) = 65.0, 3J(117Sn,H) = 62.0 Hz]. – 13C NMR (62.9 MHz,

CDCl3, DEPT135): δ = 10.04 [–, Sn(CH2CH2CH2CH3)3; Sn satellite: 2 d,

1J(119Sn,C) = 344.8, 1J(117Sn,C) = 329.6 Hz], 13.62 [+, Sn(CH2CH2CH2CH3)3], 20.87 and

20.91 (+, COCH3), 27.26 [–, Sn(CH2CH2CH2CH3)3; Sn satellite: d, 2J(Sn,C) = 59.5 Hz],

28.96 [–, Sn(CH2CH2CH2CH3)3, Sn satellite: d, 3J(Sn,C) = 19.9 Hz], 61.18 (–, C-4), 66.14

(–, C-1), 134.28 (+, C-3), 145.02 (Cquat, C-2), 170.40 and 170.65 (Cquat, COCH3).

Fraction II: 150 mg (41%) of 4-acetoxy-2-tributylstannyl-(2E)-buten-1-ol (18), colorless oil,

Rf (PE/ether 4:1) = 0.26, Rf (PE/ether 1:1) = 0.53. – IR (film): ν = 3484 cm–1 (O–H), 2958,

2924, 2871, 2853, 1743 (C=O), 1458 (CH2 and CH3 deformation), 1377, 1360, 1232 (C–O),

1031, 959, 864, 667, 598, 507. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 0.79–1.06 [m,

15 H, Sn(CH2CH2CH2CH3)3], 1.24–1.38 [m, 6 H, Sn(CH2CH2CH2CH3)3], 1.43–1.55 [m,

6 H, Sn(CH2CH2CH2CH3)3], 1.73 (t, 3J = 5.3 Hz, 1 H, OH), 2.07 [s, 3 H, COCH3;

13C satellite: d, 1J(C,H) = 129.5 Hz], 4.41 [dd, 3J = 5.3, 4J = 2.1 Hz, 2 H, 1-H; Sn satellite: d,

3J(Sn,H) = 37.4 Hz], 4.61 [d, 3J = 6.3 Hz, 2 H, 4-H; Sn satellite: d, 4J(Sn,H) = 8.8 Hz], 5.64

[tt, 3J = 6.3, 4J = 2.1 Hz, 1 H, 3-H; Sn satellites: 2 d, 3J(119Sn,H) = 66.1,

3J(117Sn,H) = 62.8 Hz]. – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 10.08 [–,

Sn(CH2CH2CH2CH3)3; Sn satellites: 2 d, 1J(119Sn,C) = 342.6, 1J(117Sn,C) = 326.8 Hz],

13.67 [+, Sn(CH2CH2CH2CH3)3], 20.97 (+, COCH3), 27.32 [–, Sn(CH2CH2CH2CH3)3;

Sn satellite: d, 2J(Sn,C) = 58.1 Hz], 29.08 [–, Sn(CH2CH2CH2CH3)3; Sn satellite: d,

3J(Sn,C) = 19.5 Hz], 61.23 (–, C-4), 63.36 [–, C-1; Sn satellite: d, 2J(Sn,C) = 20.6 Hz],

131.86 [+, C-3; Sn satellite: d, 2J(Sn,C) = 22.7 Hz], 152.17 (Cquat, C-2), 170.98 (Cquat,

COCH3). – MS (DCI, NH3), m/z (%): 442/440/438/437/436/435/434/433/432/430

(15/14/95/36/72/29/41/1/1/2) [M + NH4+], 312/310/308/307/306/305/304/303/302/300

(17/16/100/35/74/28/43/2/2/2) [Bu3SnNH3+], 165 (11) [M + NH4

+ + H + NH3 – Bu3Sn],

148 (60) [M + NH4+ + H – Bu3Sn]. – C18H36O3Sn (419.2): calc. C 51.58, H 8.66; found

C 51.46, H 8.51.

21

Fraction III: 33 mg (9%) of 4-acetoxy-3-tributylstannyl-(3E)-buten-1-ol (19), colorless oil Rf

(PE/ether 1:1) = 0.31. – 1H NMR (250 MHz, CDCl3, TMS): δ = 0.79–1.06 [m, 15 H,

Sn(CH2CH2CH2CH3)3], 1.24–1.38 [m, 6 H, Sn(CH2CH2CH2CH3)3], 1.43–1.55 [m, 6 H,

Sn(CH2CH2CH2CH3)3], 1.76 (t, 3J = 5.7 Hz, 1 H, OH), 2.07 [s, 3 H, COCH3; 13C satellite:

d, 1J(C,H) = 129.5 Hz], 4.24 [app tt, 3J = 5.8, 5J = 0.9 Hz, 2 H, 1-H; Sn satellite: d,

4J(Sn,H) = 9.0 Hz], 4.82 [dt, 4J = 2.1, 5J = 0.9 Hz, 2 H, 4-H; Sn satellite: d,

3J(Sn,H) = 39.0 Hz], 5.87 [tt, 3J = 6.0, 4J = 2.1 Hz, 1 H, 2-H; Sn satellites: 2 d,

3J(119Sn,H) = 65.0, 3J(117Sn,H) = 62.0 Hz]. – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ =

9.98 [–, Sn(CH2CH2CH2CH3)3], 13.72 [+, Sn(CH2CH2CH2CH3)3], 21.08 (+, COCH3),

27.38 [–, Sn(CH2CH2CH2CH3)3; Sn satellite: d, 2J(Sn,C) = 58.3 Hz], 29.06 [–,

Sn(CH2CH2CH2CH3)3; Sn satellite: d, 3J(Sn,C) = 19.7 Hz], 59.69 (–, C-1), 66.15 (–, C-4),

140.35 (+, C-2), 142.03 (Cquat, C-3), 170.86 (Cquat, COCH3). – C18H36O3Sn (419.2): calc.

C 51.58, H 8.66; found C 51.60, H 8.59.

It was noted that both monoacetates transacetylate intramolecularly; therefore,

chromatographic separation is necessary directly before use.

Method B (Hydrostannylation and acetylation in one pot): 2-Butyne-1,4-diol (1) (172 mg,

2.00 mmol) was suspended in a solution of Pd(OAc)2 (9 mg, 0.04 mmol, 2 mol%) and PPh3

(31 mg, 0.12 mmol, 6 mol%) in anhydrous CH2Cl2 (6 mL). On dropwise addition of tributyltin

hydride (0.59 mL, 640 mg, 2.2 mmol) at room temp. the diol dissolved completely. After

stirring for 1 h, pyridine (0.32 mL, 316 mg, 4.0 mmol) and DMAP (12 mg, 0.1 mmol) were

added, the solution was cooled to 0 °C, acetic anhydride (0.20 mL, 214 mg, 2.1 mmol) was

added, and the solution was stirred for 20 min at 0 °C and for 3 h at room temp. Workup was

done by adding H2O (8 mL), separating the phases, extracting the aqueous phase with CH2Cl2

(2 × 6 mL), washing of the combined organic phases with sat. NaCl sol. (10 mL) and drying

them over Na2SO4. Chromatography on silica gel (30 g, column 1.5 × 36 cm, PE/ether 4:1,

during elution of 18 changed to 2:1, after elution of 19 changed to 1:1) gave 170 mg (18%) of

diacetate 20, 453 mg (54%) of 18, 100 mg (12%) of 19 and 77 mg (10%) of diol 12.

Method C (Method B on large scale): To a suspension of 2-butyne-1,4-diol (1) (1.792 g,

20.8 mmol), Pd(OAc)2 (22 mg, 0.10 mmol, 0.5 mol%) and PPh3 (79 mg, 0.30 mmol,

22

1.5 mol%) in anhydrous CH2Cl2 (50 mL) was added dropwise at room temp. tributyltin

hydride (5.92 mL, 6.403 g, 22.0 mmol). The resulting solution was stirred for 1 h, mixed with

NEt3 (5.85 mL, 4.25 g, 42.0 mmol) and DMAP (102 mg, 0.83 mmol) and cooled to 0 °C.

Acetic anhydride (2.08 mL, 2.25 g, 22.0 mmol) was added, and the mixture was stirred for

20 min at 0 °C and for 3 h at room temp. Workup was done by adding H2O (50 mL) and 5%

HCl (15 mL), separating the phases, extracting the aqueous phase with CH2Cl2 (2 × 30 mL),

washing the combined CH2Cl2 phases with H2O (50 mL) and sat. NaCl sol. (50 mL) and

drying them over Na2SO4. Chromatography on silica gel (190 g, column 4.3 × 28 cm,

PE/ether 2:1, during elution of 18 changed to 1:1) and further chromatographic separation of

mixed fractions gave 1.338 g (14%) of diacetate 20, 3.392 g (39%) of 18 and 1.817 g (21%)

of 19.

Hydrolysis of 1,4-diacetoxy-2-tributylstannyl-(2E)-butene (20) to 2-tributylstannyl-(2E)-

butene-1,4-diol (12): As described in GP 3, diacetate 20 (1.338 g, 2.90 mmol) was reacted

with K2CO3 (1.04 g, 7.53 mmol) in methanol-water (35 mL / 10 mL) at room temp. for

45 min to give 1.09 g (100%) of diol 12.

4-Acetoxy-2-bromo-(2E)-buten-1-ol [(E)-3]: As described in GP 5, a solution of 4-Acetoxy-2-

tributylstannyl-(2E)-buten-1-ol (18) (1.357 g, 3.24 mmol) in CCl4 (45 mL) was reacted with a

solution of bromine (526 mg, 3.29 mmol) in CCl4 (1 mL). Chromatography on flash silica gel

[30 g, column 2.2 × 17 cm, PE/ether 2:1, during elution of (E)-3 changed to 1:1] yielded

558 mg (82%) of (E)-3 as a colorless oil, Rf (PE/ether 2:1) = 0.07. – IR (film): ν = 3427 cm–1

(O–H), 2954, 2871, 1741 (C=O), 1649 (C=C), 1442 (CH2 and CH3 deformation), 1381, 1363,

1231 (C–O), 1123, 1031, 964, 899, 822, 608. – 1H NMR (250 MHz, CDCl3, CHCl3): δ =

2.08 (s, 3 H, COCH3), 2.88 (t, 3J = 6.8 Hz, 1 H, OH), 4.42 (d, 3J = 6.8 Hz, 2 H, 1-H), 4.65

(d, 3J = 7.8 Hz, 2 H, 4-H), 6.13 (t, 3J = 7.8 Hz, 1 H, 3-H). – 13C NMR (62.9 MHz, CDCl3,

DEPT135): δ = 20.90 (+, COCH3), 60.28 (–, C-4), 63.61 (–, C-1), 127.75 (+, C-3), 131.14

(Cquat, C-2), 171.22 (Cquat, COCH3).

23

4-Acetoxy-1,2-dibromo-(2E)-butene [(E)-4]: According to GP 1 4-acetoxy-2-bromo-(2E)-

buten-1-ol [(E)-3] (558 mg, 2.67 mmol) was reacted with PPh3 (700 mg, 2.67 mmol) and

bromine (423 mg, 2.65 mmol) in CH2Cl2 (total volume 8 mL). Chromatography on silica gel

[15 g, column 1.5 × 18 cm, PE/ether 20:1, Rf (PE/ether 20:1) = 0.20] gave 381 mg (52%) of

dibromide 4 as a colorless oil, (E/Z) = 1.3:1. – IR (film): ν = 3031 cm–1, 2964, 1743 (C=O),

1642 (C=C), 1429 (CH2 and CH3 deformation), 1379, 1362, 1229 (C–O), 1100, 1031, 965,

916, 820, 630, 605, 567, 442. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 2.09 (s, 3 H,

COCH3), 4.32 (s, 2 H, 1-H), 4.57 (d, 3J = 7.4 Hz, 2 H, 4-H), 6.18 (t, 3J = 7.4 Hz, 1 H, 3-H).

– 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 20.75 (+, COCH3), 31.87 (–, C-1), 59.85 (–,

C-4), 125.62 (Cquat, C-2), 130.66 (+, C-3), 170.61 (Cquat, COCH3).

Dimethyl [4'-acetoxy-2'-bromo-(2'E)-butenyl]-2''-propenylmalonate [(E)-6]; Method A: To a

solution of dimethyl [4'-tert-butyldimethylsilyloxy-2'-bromo-(2'E)-butenyl]-2''-propenyl-

malonate [(E)-17] (118 mg, 0.271 mmol) in THF (2 mL) was added at room temp. TBAF

(1 M in THF, 0.5 mL, 0.5 mmol). After stirring for 20 min, DMAP (5 mg, 0.04 mmol) and

acetic anhydride (102 mg, 1.0 mmol) were added, and the mixture was stirred for 1 h at room

temp. The mixture was worked up by adding sat. NaCl and NaHCO3 sol. (5 mL each) and

Et2O (10 mL), separating the phases, extracting the aqueous phase with Et2O (3 × 10 mL),

washing of the combined organic phases with H2O and sat. NaCl sol. (20 mL each) and drying

them over MgSO4. Chromatography of the crude product on silica gel (5 g, column 1.5 ×

6 cm, PE/ether 2:1) gave 98 mg (100%) of (E)-6 as a colorless oil, Rf (PE/ether 4:1) = 0.14. –

IR (film): ν = 3080 cm–1, 3004 [C(sp2)-H], 2983, 2953, 2844 [C(sp3)–H], 1739 (C=O), 1643

(C=C), 1436 (CH3 deformation), 1380, 1364, 1224 (C–O), 1126, 1029, 963, 928 (CH=CH2),

858, 629, 604, 438. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.07 [s, 3 H, OCOCH3;

13C satellite: d, 1J(C,H) = 129.9 Hz], 2.76 (dt, 3J = 7.2, 4J = 1.1 Hz, 2 H, 1''-H), 3.26 (d,

4J = 0.6 Hz, 2 H, 1'-H), 3.74 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.7 Hz], 4.53 (d,

3J = 7.3 Hz, 2 H, 4'-H), 5.07–5.17 (m, 2 H, 3''-H), 5.67 (ddt, 3J = 17.4, 3J = 9.7, 3J = 7.2 Hz,

1 H, 2''-H), 6.21 (t, 3J = 7.3 Hz, 1 H, 3'-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ =

20.70 (+, OCOCH3), 36.73 (–, C-1''), 37.95 (–, C-1'), 52.69 (+, CO2CH3), 57.16 (Cquat, C-2),

24

60.71 (–, C-4'), 119.60 (–, C-3''), 124.18 (Cquat, C-2'), 131.34 (+, C-2''*), 131.99 (+, C-3'*),

170.44 (3 Cquat, CO2CH3 and OCOCH3). – C14H19BrO6 (363.2): calc. C 46.30, H 5.27;

found C 46.32, H 5.17.

Method B: As described in GP 2, dimethyl allylmalonate (5) (241 mg, 1.40 mmol) was

deprotonated with NaH (58 mg, 1.45 mmol, 60% oil suspension) and alkylated with 4-

acetoxy-1,2-dibromo-(2E)-butene (4) [381 mg, 1.40 mmol, (E/Z) = 1.3:1] in THF (6 mL),

reaction time 1 h. The crude product was purified on silica gel (10 g, column 1.5 × 12 cm,

PE/ether 4:1, changed to 2:1 during elution of 6) yielding 414 mg (81%) of 6, (E/Z) = 1.3:1.

Dimethyl [4'-Acetoxy-(2'E)-butenyl]malonate (25): According to GP 2 dimethyl malonate (24)

(5.95 g, 45.0 mmol; 2 equiv. in order to suppress dialkylation) was deprotonated with NaH

(964 mg, 24.1 mmol, 60% oil suspension) and alkylated with 1-acetoxy-4-bromo-2-butene

(22) {4.60 g, 23.8 mmol, (E/Z) mixture prepared according to ref.[9]} at 0 °C for 2 h and at

room temp. for 2 h. After removing about 2 g of 24 from the crude mixture by distilliation over

a 20 cm Vigreux column, the residue was purified by column chromatography on silica gel

(120 g, column 4.3 × 17 cm, PE/ether 2:1) and gave 4.40 g (76%) of the known[37b] 25 as a

colorless oil, Rf (PE/ether 2:1) = 0.19, (E/Z) = 7:1. – IR (film): ν = 3007 cm–1 [C(sp2)–H],

2956, 2848 [C(sp3)–H], 1737 (C=O), 1438 and 1365 (CH2 and CH3 deformation), 1347, 1234

(C–O), 1158, 1028, 972 [(E)-CH=CH], 839, 700, 643, 608. – 1H NMR (250 MHz, CDCl3,

TMS): δ = 2.06 [s, 3 H, OCOCH3; 13C satellite: d, 1J(C,H) = 129.5 Hz], 2.63–2.75 (m, 2 H,

1'-H), 3.46 (t, 3J = 7.5 Hz, 1 H, 2-H), 3.75 [s, 6 H, CO2CH3; 13C satellite: d,

1J(C,H) = 147.8 Hz], 4.50 (dd, 3J = 4.2, 4J = 0.8 Hz, 2 H, 4'-H), 5.60–5.79 (m, 2 H, 2'-H, 3'-

H). The spectroscopic data of the (Z)-isomer are in accordance with the literature.[37b]

Dimethyl [4'-acetoxy-(2'E)-butenyl](2''-bromo-2''-propenyl)malonate (27): As described in

GP 2, dimethyl [4'-acetoxy-(2'E)-butenyl]malonate (25) (4.40 g, 18.0 mmol) was reacted with

NaH (732 mg, 18.3 mmol, 60% oil suspension) and 2,3-dibromo-1-propene (26) (3.76 g,

18.8 mmol) in THF (45 mL) at room temp. for 2 h. Column chromatography of the crude

product on silica gel (120 g, column 4.3 × 16 cm, PE/ether 2:1) gave 5.60 g (86%) of 27 as an

25

(E/Z) = 7:1 mixture, colorless oil, Rf (PE/ether 2:1) = 0.21, kugelrohr distillation at 0.04 Torr

and 125 °C oven temp. – IR (film): ν = 3001 cm–1 [C(sp2)–H], 2954, 2844 [C(sp3)–H], 1737

(C=O), 1626 (C=C), 1438 (CH3 deformation), 1382, 1365, 1286, 1231 (C–O), 1149, 1027,

974 [(E)-CH=CH], 903, 856, 608, 561. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.056 (s,

3 H, OCOCH3), 2.77 (br d, 3J = 6.2 Hz, 2 H, 1'-H), 3.15 (d, 4J = 0.6 Hz, 2 H, 1''-H), 3.74 [s,

6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.49 (br d, 3J = 5.0 Hz, 2 H, 4'-H), 5.61

(d, 2J = 1.6 Hz, 1 H, 3''-H), 5.54–5.74 (m, 3 H, 2'-H, 3'-H, 3''-H). – 13C NMR (62.9 MHz,

CDCl3, DEPT135): δ = 20.61 (+, OCOCH3), 34.50 (–, C-1'), 42.99 (–, C-1''), 52.41 (+,

CO2CH3), 56.77 (Cquat, C-2), 64.15 (–, C-4'), 121.99 (–, C-3''), 126.63 (Cquat, C-2''), 128.69

(+, C-2'*), 128.85 (+, C-3'*), 170.02 (Cquat, CO2CH3), 170.27 (Cquat, OCOCH3). – MS (EI,

70 eV), m/z (%): 364/362 (0.1/0.1) [M+], 332/330 (2/2) [M+ – MeOH], 305/303 (1/1) [M+ –

OMe – CO], 283 (100) [M+ – Br], 273/271 (10/10) [M+ – HOAc – OMe], 223 (35) [M+ – Br

– HOAc], 191 (12) [M+ – Br – HOAc – MeOH], 183 (9), 171 (27), 163 (19) [M+ – Br –

HOAc – MeOH – CO], 139 (20), 105 (7), 103 (7), 91 (6), 59 (8), 43 (30) [MeCO+]. –

C14H19BrO6 (363.2): calc. C 46.30, H 5.27, Br 22.00; found C 46.19, H 5.21, Br 21.97.

Signals of dimethyl [4'-acetoxy-(2'Z)-butenyl](2''-bromo-2''-propenyl)malonate [(Z)-27]:

1H NMR (250 MHz, CDCl3, TMS): δ = 2.062 (s, 3 H, OCOCH3), 2.82 (br d, 3J = 6.7 Hz,

2 H, 1'-H), 3.17 (s, 2 H, 1''-H), 3.75 (s, 6 H, CO2CH3), 4.61 (br d, 3J = 7.0 Hz, 2 H, 4'-H), the

other signals are hidden under those of the (Z) isomer. – 13C NMR (62.9 MHz, CDCl3,

DEPT135): δ = 29.61 (–, C-1'), 52.52 (+, CO2CH3), 56.53 (Cquat, C-2), 59.88 (–, C-4'),

126.56 (Cquat, C-2''), 127.05 (+, C-2'*), 127.53 (+, C-3'*), 170.04 (Cquat, CO2CH3), 170.44

(Cquat, OCOCH3), the other signals coincide with those of the (Z) isomer.

Preparation of Enynes

1-Chloro-4-acetoxy-2-butyne (58): To a solution of propargyl chloride (55) (4.10 g,

55.0 mmol) in anhydrous Et2O (35 mL) was added at –90 to –80 °C internal temperature

(cooling with liquid nitrogen) during 5 min nBuLi (1.56 M in hexane, 32 mL, 50 mmol) and

after 5 min paraformaldehyde (1.8 g, 60 mmol) in one portion. The mixture was then stirred at

26

–40 °C for 2.5 h and at room temp. for 2.5 h. After cooling to 0 °C, acetyl chloride (3.91 mL,

4.32 g, 55.0 mmol) was added and stirring was continued at room temp. for 0.5 h. For

workup, H2O (10 mL) and sat. NaHCO3 sol. (40 mL) were added, the mixture was filtered,

the phases were separated, the aqueous phase was extracted with Et2O (3 × 40 mL), the

combined ether layers were washed with H2O and sat. NaCl sol. (100 mL each) and dried over

MgSO4. The crude product (6.5 g, yellow oil) was distilled over a 10 cm Vigreux column,

yielding 3.50 g of 58 (48%, 51% in ref.[23a] for the preparation of the alcohol), bp.

30 °C/0.05 Torr (ref.[39] 82 °C/0.5 Torr). – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 2.12 [s,

3 H, OCOCH3; 13C satellite: d, 1J(C,H) = 130.0 Hz], 4.18 (t, 5J = 2.0 Hz, 2 H, 1-H), 4.73 (t,

5J = 2.0 Hz, 2 H, 4-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 20.65 (+, OCOCH3),

30.04 (–, C-1), 52.03 (–, C-4), 80.36 (Cquat, C-2), 81.32 (Cquat, C-3), 170.12 (Cquat,

OCOCH3).

Dimethyl (4'-acetoxy-2'-butynyl)(2''-propenyl)malonate (42): Following GP 2, dimethyl allyl-

malonate (5) (1.72 g, 10.0 mmol) was reacted with NaH (420 mg, 10.5 mmol, 60% oil

suspension) and 1-chloro-4-acetoxy-2-butyne (58) (1.51 g, 10.3 mmol) in DMF (30 mL) at

room temp. for 24 h. Most of the DMF was removed at room temp. and 0.05 Torr before the

aqueous workup. The crude product was purified by chromatography on silica gel (55 g,

column 2.2 × 33 cm, PE/ether 5:1), yielding 2.15 g (76%) of 42 as a colorless oil, Rf (PE/ether

5:1) = 0.16, Rf (PE/ether 2:1) = 0.30, kugelrohr distillation at 80 °C oven temp. and

0.003 Torr. – IR (film): ν = 3080 cm–1, 3024, 2955, 2845, 2240 (C≡C), 1735 (C=O), 1642

(C=C), 1438 and 1379 (CH2 and CH3 deformation), 1328, 1220 (C–O), 1140, 1028, 969, 929,

856, 830, 658, 606, 584. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.09 [s, 3 H, OCOCH3;

13C satellite: d, 1J(C,H) = 129.9 Hz], 2.78 (d, 3J = 7.4 Hz, 2 H, 1''-H), 2.84 (t, 5J = 2.2 Hz, 2

H, 1'-H), 3.74 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.63 (t, 5J = 2.2 Hz,

2 H, 4'-H), 5.10–5.22 (m, 2 H, 3''-H), 5.62 (ddt, 3J = 17.1, 3J = 9.9, 3J = 7.4 Hz, 1 H, 2''-H). –

13C NMR (62.9 MHz, CDCl3, DEPT135): δ = 20.56 (+, OCOCH3), 22.85 (–, C-1'), 36.51 (–,

C-1''), 52.21 (–, C-4'), 52.61 (+, CO2CH3), 56.76 (Cquat, C-2), 77.19 (Cquat, C-2'), 81.49

(Cquat, C-3'), 119.76 (–, C-3''), 131.52 (+, C-2''), 169.94 (Cquat, CO2CH3), 169.99 (Cquat,

27

OCOCH3). – MS (EI, 70 eV), m/z (%): 282 (0.08) [M+], 267 (0.16) [M+ – CH3], 251 (0.6)

[M+ – OMe], 240 (4) [M+ – O=C=CH2], 223 (10) [M+ – OMe – CO], 208 (8) [M+ – OMe –

MeCO], 191 (17) [M+ – OMe – HOAc], 181 (18) [M+ – OMe – CO – O=C=CH2], 180 (23)

[M+ – OMe – CO – MeCO], 163 (77) [M+ – OMe – HOAc – CO], 162 (52) [M+ – MeOH –

HOAc – CO], 149 (10) [M+ – MeOH – OMe – CO – O=C=CH2], 139 (23), 138 (12), 131

(14) [M+ – MeOH – OMe –HOAc – CO], 121 (40) [M+ – MeOH – OMe – 2 CO –

O=C=CH2], 111 (11), 105 (9) [M+ – 2 OMe – 2 CO – OAc], 104 (11) [M+ – 2 OMe –

2 CO – HOAc], 103 (46) [M+ – MeOH – OMe – 2 CO – HOAc], 91 (17), 85 (89), 77 (13)

[C6H5+], 71 (11), 59 (19) [OAc+], 43 (100) [MeCO+], 41 (10). – C14H18O6 (282.3): calc.

C 59.57, H 6.43; found C 59.73, H 6.37.

1-Chloro-4-methoxycarbonyloxy-2-butyne (56): This compound was prepared from propargyl

chloride (55) (4.10 g, 55.0 mmol), nBuLi (1.56 M in hexane, 32 mL, 50 mmol) and

paraformaldehyde (1.8 g, 60 mmol) as described for the acetate 58, except that methyl

chloroformate (4.25 mL, 5.20 g, 55.0 mmol) was used instead of acetyl chloride. The crude

product (5.5 g, red oil) was distilled over a 10 cm Vigreux column, yielding 3.83 g of 56 (47%,

51% in ref.[23a] for the preparation of the alcohol), bp. 46–48 °C/0.05 Torr, Rf (PE/ether

5:1) = 0.41. – IR (film): ν = 3005 cm–1, 2959, 2858, 1754 (C=O), 1446 and 1376 (CH2 and

CH3 deformation), 1258 and 1158 (C–O), 1108, 1077, 1019, 956, 903, 789, 701 (C–Cl), 596,

562. – 1H NMR (250 MHz, CDCl3, CHCl3): δ = 3.83 (s, 3 H, OCO2CH3), 4.17 (t,

5J = 2.0 Hz, 2 H, 1-H), 4.79 (t, 5J = 2.0 Hz, 2 H, 4-H). – 13C NMR (62.9 MHz, CDCl3,

DEPT135): δ = 29.93 (–, C-1), 55.21 (+, OCO2CH3), 55.38 (–, C-4), 79.69 (Cquat, C-2),

82.10 (Cquat, C-3), 155.10 (Cquat, OCO2CH3). – MS (EI, 70 eV), m/z (%): 127 (100) [M+ –

Cl], 103 (4), 89/87 (9/28) [M+ – OCO2CH3], 83 (6), 77 (14), 59 (17) [CO2CH3+], 51 (36)

[C4H3+]. – C6H7ClO3 (162.6): calc. C 44.33, H 4.34; found C 44.62, H 4.51.

Dimethyl (4'-methoxycarbonyloxy-2'-butynyl)(2''-propenyl)malonate (57): According to GP 2

dimethyl allylmalonate (5) (861 mg, 5.00 mmol) was reacted with NaH (204 mg, 5.1 mmol,

60% oil suspension) and 1-chloro-4-methoxycarbonyloxy-2-butyne (56) (816 mg, 5.02 mmol)

28

in DMF (10 mL) at room temp. for 24 h. DMF was removed at room temp. and 0.05 Torr

before the aqueous workup. The crude product was purified by chromatography on 20 g of

silica gel (column 1.5 × 25 cm, PE/ether 2:1) yielding 1.16 g (78%) of 57 as a colorless oil, Rf

(PE/ether 4:1) = 0.11, Rf (PE/ether 2:1) = 0.21, distillation in a microsublimation apparatus

heated to 110 °C at 0.02 Torr. – IR (film): ν = 3080 cm–1, 3006, 2957, 2846, 2239 (C≡C),

1755 (C=O carbonate), 1736 (C=O ester), 1642 (C=C), 1444 and 1376 (CH2 and CH3

deformation), 1327, 1268, 1221 (C–O), 1140, 1070, 1026, 997, 954, 902, 856, 792, 734, 658,

578. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.78 (d, 3J = 7.4 Hz, 2 H, 1''-H), 2.84 (t,

5J = 2.2 Hz, 2 H, 1'-H), 3.74 [s, 6 H, CO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 3.81 [s,

3 H, OCO2CH3; 13C satellite: d, 1J(C,H) = 147.8 Hz], 4.69 (t, 5J = 2.2 Hz, 2 H, 4'-H), 5.10–

5.22 (m, 2 H, 3''-H), 5.61 (ddt, 3J = 17.1, 3J = 9.9, 3J = 7.4 Hz, 1 H, 2''-H). – 13C NMR

(62.9 MHz, CDCl3, DEPT135): δ = 22.89 (–, C-1'), 36.55 (–, C-1''), 52.76 (+, CO2CH3),

55.03 (+, OCO2CH3), 55.72 (–, C-4'), 56.78 (Cquat, C-2), 76.63 (Cquat, C-2'), 82.51 (Cquat,

C-3'), 119.95 (–, C-3''), 131.50 (+, C-2''), 155.09 (Cquat, OCO2CH3), 170.02 (Cquat,

CO2CH3). – MS (EI, 70 eV), m/z (%): 283 (0.05) [M+ – CH3], 267 (0.1) [M+ – OMe], 239

(3) [M+ – OMe – CO], 223 (14) [M+ – OMe – CO2], 191 (18) [M+ – MeOH – OMe – CO2],

163 (100) [M+ – MeOH – OMe – CO2 – CO], 162 (71) [M+ – 2 MeOH – CO2 – CO], 147

(10) [M+ – 2 MeOH – OMe – 2 CO], 139 (15), 135 (14), 131 (17) [M+ – 2 MeOH – OMe –

CO2 – CO], 119 (9) [M+ – 2 MeOH – OMe – 3 CO], 105 (12), 104 (11), 103 (50) [M+ –

2 MeOH – OMe – 2 CO – CO2], 91 (17), 77 (16) [C6H5+], 59 (31), 41 (10). – MS (DCI,

NH3), m/z (%): 316 (100) [M + NH4+]. – C14H18O7 (298.3): calc. C 56.37, H 6.08; found

C 56.54, H 6.13.

1,4-Dibromo-2-butyne (59): According to ref.[43] 2-butyne-1,4-diol (1) (2.15 g, 25.0 mmol)

was reacted with PBr3 (1.72 mL, 4.90 g, 18.1 mmol) in Et2O (10 mL). The crude product

contained 59 and 1,2,4-tribromo-(2Z)-butene (identified by comparison with 1H-NMR data

from ref.[44]) in a 7.6:1 ratio. After distillation at 0.5 Torr one obtained 3.10 g (58%) of 59,

bp. 42–44 °C, ratio 59/1,2,4-tribromo-(2Z)-butene about 50:1. – 1H NMR (250 MHz, CDCl3,

TMS): δ = 3.96 [s, 4 H, 1(4)-H; 13C satellite: dt, 1J(C,H) = 159.1, 5J(H,H) = 2.3 Hz].

29

Dimethyl (4'-bromo-2'-butynyl)(2''-propenyl)malonate (60): According to GP 2 dimethyl allyl-

malonate (5) (1.72 g, 10.0 mmol) was reacted with NaH (420 mg, 10.5 mmol, 60% oil

suspension) and 1,4-dibromo-2-butyne (59) (6.29 g, 29.7 mmol; 3 equiv. in order to suppress

dialkylation) in THF (25 mL); however, the solution of the malonate (in 20 mL of THF) was

added to the dibromide (inverse addition) and stirred afterwards at room temp. for 2 h. The

crude product was chromatographed on silica gel (70 g, column 2.9 × 24 cm, PE/ether 10:1,

after complete elution of 59 changed to 4:1) yielding fraction I: 4.10 g (19.4 mmol, 65%

recovery) of 1,4-dibromo-2-butyne (59). – Fraction II: 2.58 g (85%) of bromoenyne 60,

colorless oil, bp. ≈ 90 °C/0.02 Torr, Rf (PE/ether 9:1) = 0.24, Rf (PE/ether 4:1) = 0.29. – IR

(film): ν = 3079 cm–1, 3006, 2981, 2954, 2843, 2237 (C≡C), 1738 (C=O), 1642 (C=C), 1437

(CH2 and CH3 deformation), 1327, 1292, 1250, 1216 (C–O), 1141, 1070, 1029, 996, 969,

929, 856, 820, 657, 612, 582. – 1H NMR (250 MHz, CDCl3, TMS): δ = 2.79 (d, 3J = 7.5 Hz,

2 H, 1''-H), 2.86 (t, 5J = 2.3 Hz, 2 H, 1'-H), 3.75 [s, 6 H, CO2CH3; 13C satellite: d,

1J(C,H) = 147.8 Hz], 3.88 (t, 5J = 2.3 Hz, 2 H, 4'-H), 5.11–5.25 (m, 2 H, 3''-H), 5.61 (ddt,

3J = 17.2, 3J = 9.8, 3J = 7.5 Hz, 1 H, 2''-H). – 13C NMR (62.9 MHz, CDCl3, DEPT135): δ

= 14.75 (–, C-4'), 23.12 (–, C-1'), 36.65 (–, C-1''), 52.84 (+, CO2CH3), 56.87 (Cquat, C-2),

78.39 (Cquat, C-2'), 82.17 (Cquat, C-3'), 120.07 (–, C-3''), 131.51 (+, C-2''), 170.09 (Cquat,

CO2CH3). – MS (EI, 70 eV), m/z (%): 305/303 (0.4/0.4) [M+ + H], 273/271 (1/1) [M+ –

OMe], 245/243 (2/2) [M+ – OMe – CO], 244/242 (2/2) [M+ – MeOH – CO], 241/239 (2/2)

[M+ – OMe – MeOH], 223 (52) [M+ – Br], 213/211 (1/1) [M+ – OMe – MeOH – CO], 191

(4) [M+ – Br – MeOH], 185/183 (2/3) [M+ – OMe – MeOH – 2 CO], 171 (10) [M+ –

BrCH2C≡CCH2], 164 (11) [M+ – Br – OMe – CO], 163 (100) [M+ – Br – MeOH – CO], 150

(5), 139 (17) [M+ – BrCH2C≡CCH2 – MeOH], 131 (10) [M+ – Br – 2 MeOH – CO], 105

(13) [M+ – Br –2 OMe – 2 CO], 104 (12) [M+ – Br – MeOH – OMe – 2 CO], 103 (26) [M+ –

Br – 2 MeOH – 2 CO], 91 (10), 79 (6), 77 (10) [C6H5+], 59 (19) [MeOCO+], 41 (7). –

C12H15BrO4 (303.2): calc. C 47.54, H 4.99; found C 47.43, H 5.08.