Chapter 4

The Catalytic Chemistry of Palladium (II)

G. Poli

Main “Non-organometallic” Pd (II) Sources

=

2 LiCl2 MeCN

=

insoluble

soluble

PdCl

PdCl

ClPd

Cl

Cl Cl[PdCl2]n

2 PPh3

PdCl2(MeCN)2 PdCl2(PPh3)2 Li2PdCl4

Pd(OAc)2 PdO

O

O

OMe Me

n

Pd(MeCN)4(BF4)2

2 AgBF42 MeCN2 AgCl

G. Poli

Oxidative Palladations

[Pd(II)X2] ____→ [Pd(0)] ____→ [Pd(II)X2][Ox]

G. Poli

Reactivity of a Pd(II)-coordinated Alkene

X[Pd]X

.RH

HX

Nu

X[Pd]

Nu

R

H

σ-alkyl-Pd

PdX2

anti palladationNu: H2O, X-, carbanions…

R'[Pd]X

.RH R' [Pd]X

RH

σ-alkyl-Pd

R'[Pd]X HH H

syn palladation

as in Mizoroki-Heck chemistry

Addition of Nucleophiles to Alkenes: General Reactivity

PdCl2RPd

ClCl

Pd ClCl

R

R NuA

add. to the most substituted C atom

R NuA

Cl[Pd](in solution)

stoichiometric reactions

R NuA

R NuA

Cl[Pd] H[Pd(0)] + HCl

R

NuA

Cl[Pd]

NuB

R

NuANuB

NuA = H2O

R

O

Cl[Pd]

HH

[Pd(0)] + HCl

H3C

O

R

A

B

C

dehydropalladation

displacement

hydride shift

[Pd(0)] + Cl

Typical nucleophiles known to react with the coordinated alkenes: water, alcohols, carboxylic acids, ammonia, amines, enamines and active methylene compounds.

See later the detailed mechanism

Tsuji, J. Acc. Chem. Res. 1969, 2, 144G. Poli

Hydroxypalladation

stoichiometric reactionsdepending on the reaction conditions the intermediate β-hydroxypalladium complex may suffer either hydride shift or displacement

PdCl2 OCl[Pd] H

H

[Pd(0)] + HCl

CH3CHOhydride shift

H2O+hydroxypalladation

displacement

PdCl2, LiCl OHCl[Pd]H2O+

Clhydroxypalladation

OHCl[Pd(0)] + Cl

Smidt, J.; Hafner, W.; Jira, R.; Sieber, R.; Sedlmeier, J.; Sabel, J. Angew. Chem. Int. Ed. Engl. 1962, 1, 80

G. Poli

Catalytic Hydroxypalladation: the Wacker Process

This is the industrial process for acetaldehyde production from ethylene, developed simultaneously by Wacker-Chemie and by the group of Moiseev (1959).

PdCl2 cat, CuCl2 catCH3CHO

H2O, HCl, O250-130 °C, 3-10 atm

95%

C2H4 + PdCl42- + 3H2O -----> H3CCHO + Pd(0) + 2H3O+ + 4Cl-

Pd(0) + 2CuCl2 + 2Cl- ------> PdCl42-+ 2CuCl

4CuCl + 4H3O+ + 4Cl- + O2 -----> 4CuCl2 + 6H2O

C2H4 + 1/2 O2 ------> H3CCHO

Oxidation of Pd(0), a noble metal, with CuCl2, a base metal salt, is expected to be very difficult !The CuCl is easily reoxidized to CuCl2 with oxygen.

G. Poli

Smidt, J.; Hafner, W.; Jira, R.; Sedlmeier, J.; Sieber, R.; Rüttinger R.; Kojer, H. Angew. Chem., 1959, 71, 176.Feringa, B. L. in Wacker Oxidation, Transition Metals for Organic Synthesis, Beller, M. and Bolm, C. Ed., Wiley-VCH, 1998, chapter 2.8, pp 307-315.

The Mechanism of the Wacker Process

PdH2O

Cl ClOH Pd

H2O

ClOH

H HPd

H2O

Cl HOH

dehydro-palladation

PdH2O

Cl O

CH2H

H

insertion

Pd(0)

HCl

H

PdCl

Cl Cl

PdCl2

CH3CHOHCl, H2O, PdCl2 cat, CuCl2 cat, O2

Cl-

PdH2O

Cl Cl

H2O Cl- H2O

H+

O HH

Cl-

2 CuCl22CuCl

1/2 O2 + 2HCl

chloride mediatedreductive elimination

The anti hydroxypalladation is likely due to the presence of chloride anion

Bäckvall, J. E.; Åkermark, B.; Ljunggren, S. O.; J. Am. Chem. Soc. 1979, 101, 2411Keith, J. A.; Oxgaard, J.; Goddard, W. A. J. Am. Chem. Soc. 2006, 128, 3132-3

G. Poli

The Mechanism of the Wacker Process

The detailed mechanism of the hydride shift

CH2DCHO + [Pd(0)]

hydride shiftPd

H2O

Cl ClOH

PdH2O

ClOH

H H

Cl- dissociation(rate det. step)

PdH2O

Cl HOHdehydropalladation

no enoldecoordination

PdH2O

Cl O

CH2H

H

insertion

CH3CHO + [Pd(0)]

HCl H2OH

HCl H2OD2O

HO

H

H OH1/2O2 O

H

H+ + +

cat.

The reaction is formally a dehydrogenative coupling

G. Poli

The Tsuji Variation of the Wacker ReactionHigher alkenes can be oxidized to ketones in solvents that dissolve both the alkene and water (DMF). Stoichiometric oxidants (benzoquinone, O2/CuCl2, S2O8, MeONO… ) can be used to re-oxidize Pd(0) to Pd(II). The attack obeys the Markovnikov rule. Thus, terminal alkenes can be viewed as masked methyl ketones.

O PdCl2 cat. CuCl catO2, H2O, DMF (68%)

O

O

OAc

PdCl2 cat. CuCl catO2, H2O, DMF (~80%)

OAc

O

CO2Me

Na2PdCl4 cat.t-BuOOH, i-PrOH(64%) CO2Me

O

OOBnOO

OEDMSOBn

PdCl2 cat. H2O, DMF 45°C, (60%)

OOBnOO

OEDMSOBn

O

OOBnO

OEDMSOBn

O

terminal alkenes are more reactive than internal ones.

taxol derivative

good method to obtain 1,4-diketones

regioselective reaction with Michael acceptors. In this case the peroxide, and not H2O, is the nucleophile.

Tsuji, J. Comprehensive Organic Synthesis 1991, vol 7, 449Iwadare, H.; Satoh, H.; Arai, H.; Shiina, I.; Mukaiyama, T. Chem. Lett. 1999, 817

G. Poli

Alkoxypalladation

stoichiometric reactionhydride shift and dehydropalladation may be competitive paths

+ MeOHPdCl2, base

methoxypalladation

OMeCl[Pd]

H hydride shiftH3C

OMe[Pd(0)]base HCl

H3COMe

OMe

OMe

Cl[Pd] H

dehydropalladation

[Pd(0)] + HCl

OMe

major

minor

MeOH

Cl [Pd(0)] + HCl

G. Poli

Alkoxypalladation

Efficient reoxidation of Pd(0) to Pd(II) is sometimes possible (without copper) in the presence of special ligands such as DMSO or pyridine. In this latter case the oxidation is expected to pass through a peroxopalladium(II) complex

Py2Pd(0)O2

Py2PdO

Operoxopalladium(II)complex

2 HClH2O2 + Py2PdCl2

Stahl, S. S.; Thorman, J. L.; Nelson, R.C.; Kozee, M. A. J. Am. Chem. Soc. 2001, 123, 7188

OH

Pd(OAc)2 5 mol%DMSO, O2 (95%)

OO+

95 : 5

H

H

H

H

Rönn, M.; Bäckvall, J. E.; Andersson, P.G. Tetrahedron Lett. 1995, 36, 7749

G. Poli

Alkoxypalladation

Carbonylative oxidation

OMe

O

OHH PdCl2 (5mol%)

CuCl2 (2equiv.)CO, MeOH

OMe

O

HO

CO2Me

Propose a plausible mechanism for this transformation

Phenolic oxygen atoms participate easily in oxypalladations:Review: Hosokawa, T.; Murahashi, S. Heterocycles, 1992, 33, 1079

97% ee

Pd(MeCN)4(BF4)2L*, benzoquinone

MeOH, 25°C (90%)OH O

N

O

N

O

L* = (S,S)-ip-boxax

Uozumi, I.; Kato, K. Hayashi, T.J. Org. Chem. 1988, 63, 5071

G. Poli

Alkoxypalladation

The stereochemistry of the alkoxypalladation may be syn or anti depending on the reaction conditions. The origin of this delicate balance has not been completely elucidated. The presence of chloride anions has been evoked as a possible reason for anti addition.

bis[acetoxy(3,2,10-η3-pinene)Pd(II) (10%)Cu(OAc)2 10%O2, MeOH reflux (82%)

OH

PdAcO

2

bis[acetoxy(3,2,10-η3-pinene)Pd(II)mainly this isomervia syn oxypalladation

D

O

H

PdCl2(MeCN)2 (10%)benzoquinone (1.0 equiv;)Na2CO3 (2.0 equiv.) LiCl (2.0 equiv;)THF, reflux (59%)

OH Omainly this isomer and mainly via anti oxypalladation followedby dehydroPd, hydropd...

D

D

Hayashi, T., Yamasaki, K.; Mimura, M. M.; Uozumi, Y J. Am. Chem. Soc.. 2004, 126, 3036-7Trend, R. M.; Ramtohul, Y. K.; Stolz, B. M. J. Am. Chem. Soc. 2005, 127, 17778-88 G. Poli

Alkoxypalladation

Syn alkoxypalladation

O OX[Pd]HOHX

X[Pd]

PdX2

OHX

Anti alkoxypalladation

HO O

X[Pd]

HOHX

PdX2

OHXHX

G. Poli

Acetoxypalladation

stoichiometric reaction

Industrial production of vinyl acetate (Kuraray). Pd supported on silica or alumina is used as a catalyst. Pd oxidation is expected to take place on the surface of the support.Pd(OAc)2

OAc

AcO[Pd] H

acetoxypalladationdehydropalladation(AcO is EWG: no H-shift)

[Pd(0)] + AcOH

OAc

catalytic reaction

AcOH

1/2 O2

+OAcgas phase

Pd(0)/SiO2 + 2AcOHPd(AcO)2/SiO2

H2O

Nakamura, S.; Yasui, T.J. Catal. 1976, 17, 366

G. Poli

Allylic Acetoxylation of Cyclohexene

The acetoxylation of cyclohexene does not proceed via acetoxypalladation as for ethylene and affords allylicoxidation. Labeling experiments unveiled that a η3-allyllpalladium complex is involved.

OAc

OAcPd(OAc)2 cat.AcOHbenzoquinone

Pd

H AcOHHO

OAc

O OAc

[Pd(0)]

[Pd(0)]Pd(OAc)2

Pd

OO

O

OBQ

O

O

2 AcOH

O

O

HO

OH

Grennberg, H. and Bäckvall, J.E. Chem. Eur. J. 1998, 4, 1084

G. Poli

Intramolecular Carboxylation of Alkenes

Pd(TFA)2 (10 mol %), pyridine (40 mol%)Na2CO3 (2.0 equiv.), MS3Å, 1 atm O2, tol 80°C (86%)

CO2H

OO

CO2EtCO2Et

CO2H

D

OO

CO2EtCO2EtH

CO2EtCO2Et

CO2H

D

OO

CO2EtCO2EtD

Pd(TFA)2 (10 mol %)pyridine (20 mol%)Na2CO3 (2.0 equiv.),MS3Å, 1 atm O2, tol 80°C (86%)

Experiments with deuteratedsubstrates showed the operation of an anti carbopalladation mechanism

Trend, R. M.; Ramtohul, Y. K.; Stolz, B. M. J. Am. Chem. Soc. 2005, 127, 17778-88G. Poli

Aminopalladation

NH2

PdCl2(MeCN)2

NH2

PdCl

Clstable

Aliphatic amines coordinate Pd(II) too strongly to promote aminopalladation. On the other hand, nitrogen-based nucleophiles with reduced availability of the N lone pair (acetamides, tosylamides, anilines) do undergo catalytic aminopalladation.

HN

PdCl2(MeCN)2

O

N

OPd

HN O

PdClCl

Cl

stable

NH

PdCl2(MeCN)2 (1 mol%)

NTs

Ts

benzoquinone (1.0 equiv.)LiCl, THF (60-90%)

NRH

PdCl2(MeCN)2 (2 mol%)

benzoquinone (2.0 equiv.)LiCl, THF (60-86%)

R = H, Ac, TsNR

Hegedus, L. S.; Comprehensive Organic Synthesis, 1991, 4, 551, 571G. Poli

Aminopalladation

NH

py2Pd(OAc)2 catO2 (1atm), xylene80°C, (87%)

NTsTs

Fix, S. R.; Brice, J. L.; Stahl, S. S. Angew. Chem. Int. Ed. 2002, 41, 164

G. Poli

1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes

Pd(OAc)2 cat.LiOAcbenzoquinoneAcOH, LiCl

Pd(OAc)2 cat.LiOAcbenzoquinoneAcOH

Pd(OAc)2 cat.LiOAcbenzoquinoneAcOH, LiCl cat.

Cl

OAc

AcO

OAc

AcO

OAc

Bäckvall, J.-E. in Metal-Catalyzed Cross Coupling Reactions, Stang, P. J.; Diederich, F. Eds., Wiley - VCH, Weinheim, 1998, p. 339.

G. Poli

1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes

Pd(OAc)2

PdAcO OAc

O

O

X

X

PdAcO

O

OY

YX

O

O

Pd(0)

2H

OH

OH

X

AcOAcO

G. Poli

1,4-Chloroacetoxylation and Diacetoxylation of 1,3-Dienes

Cl-

OAcClCl-

Cl-

AcO-

PdCl BQ

OAc

PdL L

Cl

PdL L

Pd(OAc)2 cat., LiOAc, benzoquinone, LiCl, AcOH

-OAc

PdL L

PdL L

Cl

PdCl BQ

OAc

OAcOAc

Cl-

AcO-

Pd(OAc)2 cat., LiOAc, benzoquinone, LiCl cat. AcOH

PdL L

PdO BQ

OAc

O

Me

OAc

AcO

AcO-

Pd(OAc)2 cat., LiOAc, benzoquinone, AcOH

Bäckvall, J.-E. in Metal-Catalyzed Cross Coupling Reactions, Stang, P. J.; Diederich, F. Eds., Wiley - VCH, Weinheim, 1998, p. 339.

G. Poli

Oxidative Carbocyclization of Allene-Substituted Olefins

.

MeO2C CO2Me MeO2CCO2Me

Pd(O2CCF3)2 (10%),BQ (20%), FePc (10%), O2, Tol 95°C

MeO2C CO2Me

MeO2CCO2Me

Pd(II)

Pd(0)

O

O

OH

OH

FePc(ox)

FePc(red) ½ O2

H2O

N N

N

N N

N

NN FeFePc =

Piera, J.; Närhi, K.; Bäckvall, J.-E. Angew. Chem. Int. 2006, 45, 6914-6917

Oxidative Carbocyclization of Allene-Substituted Olefins

.

CO2MeMeO2C

Pd

H(D)H

allene-attackon Pd(II)

syn C-H clevage by Pd(II)

CO2MeMeO2C

Pd

H(D)H

.

CO2MeMeO2C

Pd(D)H

olefin insertion

alleneinsertion

MeO2C CO2Me

MeO2C CO2Me

H

(D)HF3CCO2[Pd]

[Pd]O2CCF3(D)H

MeO2C CO2Me

(D)H

F3CCO2 O2CCF3O2CCF3

F3CCO2

CF3CO2Pd(D)HPd(0)

CF3CO2(D)H

[Ox]

Pd(II)

dehydropd

.

CO2MeMeO2C

H(D)H

Pd(II) coord

CF3CO2H

.

CO2MeMeO2C

Pd

H(D)H

F3CCO2 O2CCF3

reaction OK no reaction

MeO2C CO2Me

.

CO2MeMeO2C

A mechanism involving π-allyl intermediates (see low path) is ruled out by the results obtained using the substrates showed at the left.

Oxidative Carbocyclization of 1,3-Dienyl Allenes

MeO2C CO2MeAcO

Pd(OAc)2 (10 mol%)Li2CO3 (5 equiv.)BQ (2 equiv)AcOH (20 equiv)acetone, rt, 20 h, (79%)

MeO2C CO2Me

[Pd]OAc

MeO2C CO2Me

.

MeO2C CO2Me

Pd

BQAcO

syn vinyl-Pd alkene carbopd

H[Pd(II)]

AcOH

anti acetateadd

allene addto [Pd(II)]

AcOH

[Pd(0)][Pd(II)]

BQ

HQ

BQ

H[Pd]OAcred elim

BQ

Löfstedt, J.; Franzén, J.; Bäckvall, J. E. J. Org. Chem. 2001, 66, 8015Löfstedt, J.; Närhi, K.; Dorange, I.; Bäckvall, J.-E. J. Org. Chem. 2003, 68, 7243-7248.

Oxidative Carbocyclization of Indoles

Cyclization via the indol nitrogen can be obtain by Pd(0) catalysis (see chapter 3)

NH

O

NMe

NH

PdCl2(MeCN)2 cat, BQ, THF-DMF 80°C, (98%) N

O

Me

Me

N

HO

NMe

PdX2

NH

N

O

Me

[Pd]X

NH

N

O

Me

H[Pd]X

X

HXH

H[Pd]X[Pd(0)]

BQHQ

[Pd(II)]

HX

N

H

O

NMe

X2PdHX

N

HO

NMe

[Pd]X

NH

N

O

Me

X[Pd]

carbopd

dehydropd

dehydropd

orthopd

1st hypothesis

2nd hypothesis

carbopd

Abbiati,G.; Beccalli, E.M.; Broggini, G.; Zoni, C. J. Org. Chem. 2003, 68, 7625-7628G. Poli

Oxidative Mizoroki-Heck Coupling

Coupling of organometallic compounds of B, Sn and Si with alkenes as a halogen-free oxidative Mizoroki-Heck type reaction takes place with catalytic amounts of Pd(II) in the presence of oxidants. In this particular case the catalytic cycle starts with a transmetallation rather than an oxidative addition.

Ph BOH

OHCO2Me

Pd(OAc)2, O2, Na2CO3DMF, 50°C, 87%

CO2Me

Ph

Ph [Pd] OAc

transmetallation

B OAcHO

HO

CO2MeCO2Me

Ph[Pd]OAc

insertion CO2MePh

[Pd]OAcH

H[Pd]OAc[Pd(0)]

1/2 Na2CO3

AcONa 1/2 H2O + 1/2 CO2

conformationalchange

dehydropalladationoxidation[Pd(II)]

Jung, J.C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett. 2003, 5, 2231Cho, C. S.; Uemura, S. J. Organometal. Chem. 1994, 465, 85Hirabayashi, K.; Ando, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Synlett,. 1999, 99

G. Poli

Non-oxidative Palladations

[Pd(II)] ____→ [Pd(II)]

G. Poli

Palladations followed by deoxypalladations

G. Poli

Acetoxypalladation / Carbopalladation

OO

Me

OAcPd(OAc) cat.AcOH, L

OO

AcO

Me

OO

MeOAc

[Pd]OAc

trans acetoxypalladation

carbopalladation

OO

AcO

Me

OAc

[Pd]OAc

deacetoxypalladation

N N

N

O

N

O

(92% ee)

Ligands

4-acetoxy-2-butenyl-2-alkynoate

AcO

In the presence of halide ligands, chloropalladation (instead of acetoxypalladation) takes place. Excess of halide inhibits dehydropalladation

Lu, X.; Zhang, Q. J. Am. Chem. Soc., 2000, 122, 7604

G. Poli

Aminopalladation

NBoc

MOMOOBn

OBn

OH

PdCl2(MeCN)2(15 mol%)

NBoc

MOMOOBn

OBn

NH

HOOH

OH

1-deoxymannojirimycin

NBoc

MOMOOBn

OBn

OH

PdCl2NBoc

MOMOOBn

OBn

[Pd]Cl

OH

Pd(II)

diastereoselective

Yokoyama, H.; Otaya, K.; Kobayashi, H.; Miyazawa, M.; Yamagichi, S.; Hirai, Y. Org. Lett. 2000, 2, 2427

G. Poli

Aminopalladation

LiBr is essential to promote the desired deacetoxypalladation

NH

O O

Ts X

OO Pd(OAc)2, LiBr O

NO

Ts

OO

diastereoselectiveNH

HO OH

OH

X = OAc, OCONHTs

Lei, A.; Liu, G.; Lu, X. J. Org. Chem. 2002, 67, 974

G. Poli

Cycloisomerisations

Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215Trost, B. M.; Krische, M. J. Synlett 1998, 1.Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. Rev. 1996, 96, 635.Trost, B. M. Janssen Chimica Acta, 1991, 9, 3.

G. Poli

Cycloisomerization of 1,6-enynes

Other transition metals such as Rh, Ru, Pt are capable of effecting cycloisomerisationwith or without skeletal rearrangements of 1,6-enynes. 1,6-dienes can also undergo similar cycloisomerizations

RH

R

Hintramolecular Alder-ene

thermal (very high temperatures)

CC

CH2

C C RR

HPd(II) cat. intramolecular Alder-ene

R

Hand/or

C CH

CH2

Pd(II) cat. skeletal rearrangement(Ring Closing Metathesis)

R' R' R'

CC

CH2

H H

regular bondconnectivity

anomalous bondconnectivity

and

(via Pd hydride or oxidative cyclization mechanism)

(via oxidative cyclization)

Typical catalytic systems:

1. Pd(OAc)2 / PAr3; 2. Pd2(dba)3 / AcOH; 3. [Pd(MeCN)4]2+; 4. TCPC / P(OAr)3

Pd CO2MeMeO2C

CO2MeMeO2C

(TCPC)

The mechanism of these completely atom economical cyclizations is still matter of speculation. Catalytic systems 1-3 are expected to follow the Pd hydride mechanism, whereas catalytic system 4 is supposed to trigger oxidative cyclization.

G. Poli

The Hydridopalladium Mechanism

No redox in the catalytic cycle !

H

H

[Pd]OAc

H

H

Hand/or

H

H

Pd OAc

H

H[Pd]OAc

H

H

H[Pd]OAc

[Pd(II) or Pd(0)] cat.

hydropalladation carbopalladation

dehydropalladation

1,4-diene 1,3-diene

The RCO2[Pd]H species is expected to be generated in situ via: a) oxidative addition of [Pd(0)] on a carboxylic acid (i.e. AcOH or HCO2H)b) interaction between the Pd(O2CR)2 and adventitious H2O)

a) [Pd(0)] + AcOH AcO[Pd]H

b) Pd(O2CCF3) + H2O CF3CO2[Pd]H + CF3CO2H

G. Poli

The Oxidative Cyclization Mechanism

H

H

and/or

H

H

[Pd(0 or II)] [Pd(II or IV)]

H

[Pd(II or IV)]

H H

[Pd(II or IV)]Hand/orH

[Pd(0 or II)]

oxidativecyclization dehydroPd

reductiveelimination

[Pd(0 or II)] cat

G. Poli

1,3 Versus 1,4-Dienes as Products

Hydridopalladium Mechanism Oxidative Cyclization Mechanism

In the oxidative cyclization mechanism, exchange between R-Pd-H and AcOH after beta-elimination, but prior to reductive elimination cannot be ruled out.

[Pd(IV)]

Ha[Pd(II)]

Hb

Ha

[Pd(II)]Hb

Hb

Hb[Pd]OAc

Ha

H

1,4-diene

1,3-diene

H

H

R

R'

R

R

R

R'

R'

R'Ha

Hb

R

R'

R

R' Ha

H

H

R

R'

H

H

AcO[Pd]H [Pd(II)]R'

Independently of the operating mechanism, dehydropalladation normally takes place on Ha thereby affording a 1,4-diene. However, such a preference can be switched to favor the 1,3-diene if: a) stericcongestion is increased around Ha, b) CHa is bound to an EWG group, c) a juxtaposed unsaturationon R blocks the conformational freedom via coordination to Pd. All these factors inhibiting dehydropalladation via Ha.

G. Poli

Cycloisomerizations Leading to 1,4-Dienes

OMePMBO

(Ph3P)2Pd(OAc)2 cat.PhH, 70°C (77%)

OMe

PMBO

MeO2C

MeO2C

Pd(OAc)2 5%DCE, 60°C, (39%)

MeO2C

MeO2C

only

CO2Me

CO2Me

CO2Me

CO2Me

CO2Me

CO2Me

(Ph3P)2Pd(OAc)2 cat.THF, 66°C, (85%)

the thermal cyclization failed

G. Poli

Cycloisomerizations Leading to 1,3-Dienes

Allylic carbon bound to a heteroatom

Steric congestion at the allylic substituent

Remote binding

No external allylichydrogen: no choice

[Pd(IV)]

HaHbHb

[Pd]OAcMeO2C

MeO2C

Ha

or

OMePMBO

Pd(OAc)2C6D6, 60°C (96%)

N NPhPh (BBEDA)

PMBO OMe

OTBDMSPMBO

(oTol3P)2Pd(OAc)2Tol, 80°C, (80%)

PMBOOTBDMS

1,3-diene

MeO2C

MeO2C(Ph3P)2Pd(OAc)2 5%THF, 66°C, (64%)

MeO2C

MeO2C

MeO2C

MeO2CPd(OAc)2 5%PhH, 60°C, (82%)

MeO2C

MeO2C

1,3 : 1,4 = 15 : 1

G. Poli

Asymmetric Cycloisomerization of 1,6-enynes

O

CO2Me [(MeCN)4Pd](BF4)2 (5 mol %)(S)-Xyl-SEGPHOS (10 mol%)DMSO, 80°C (> 99% y, 96% ee)

O

CO2MeR O

OO

O

PP

H[Pd]+[BF4]-

O

CO2Me

[Pd]+[BF4]-H

O

[Pd]+[BF4]-

CO2Me

H

O

CO2Me

[Pd]+[BF4]-H

(S)-Xyl-SEGPHOS

[(MeCN)4]Pd](BF4)2

traces of H2O

hydropalladation carbopalladation

dehydropalladation

Hatano, M.; Terada, M.; Mikami, K. Angew. Chem. Int. 2001, 40, 249

G. Poli

Pd(0)-Catalyzed Cycloisomerization of 1,6-Alkenyl Allenes

MeO2C CO2MeMeO2C CO2Me

Pd(dba)2 (5 mol%)

AcOH, 120 οC8 minutes (83%)

+

MeO2C CO2Me

88 : 12

.

MeO2C CO2Me

(D)HPdOAc

PdAcO H(D)

MeO2C CO2MeCO2MeMeO2C

[Pd]

(D)

OAc

MeO2CCO2Me

[Pd](D)

AcO

MeO2CCO2Me

(D)

[Pd(0)] + (D)HOAc

hydroPd

olefininsertion

dehydropd.

n = 0, 1

( ) ( ) ( )

( )( )

n n n

nn

..

-HPdOAc

oxidativeaddition

Närhi, K.; Franzén, J.; Bäckvall, J. E. Chem. Eur. J. 2005, 11, 6937-6943

Palladium (II) as Lewis Acid

(no organopalladium species involved)

G. Poli

Palladium Enolates

Preparation of the aqua and the hydroxy Pd complexes

PPh2

PPh2

PdCl2 2AgOTfwet DMFmol. sieves

2AgCl

CP

CP

(R)-BINAP

Pd

O OH HH H

2+2TfO

aqua Pd complex A

NaOH CP

CP

Pd

O

OH

H

CP

CPPd

dinuclear Pd(µ-OH) complex B

2TfO

enantioselective aldol condensation mechanism

Ph

OSiMe3

1. PhCHO cat A (1 mol%) tetramethylurea 0°C2. H3O+

Ph

O OH

Ph92%, 89%ee

Ph

OPd

P

P

2+OMe3Si

HH

TfOH, Me3SiOH

2TfO

Ph

OPd

P

P

2+OH

H 2TfO

Pd enolate

H2O

Yamashima, Y.; Sodeoka, M. The Chemical Record, 2004, 4, 231-242

G. Poli