the first allylation of esters by an allylsilane: one-pot domino synthesis of triallylmethane...

DOI: 10.1002/adsc.201400296

The First Allylation of Esters by an Allylsilane: One-Pot DominoSynthesis of Triallylmethane Derivatives

Chenna Kesava Reddy Bandi,a Anatoly Belostotskii,a and Alfred Hassnera,*a Department of Chemistry, Bar-Ilan University, Ramat-Gan, 52900, Israel

Fax: (+972)-3-738-4053; e-mail: [email protected]

Received: March 25, 2014; Published online: June 24, 2014

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400296.

Abstract: We report the first successful allylation ofaromatic esters by allyltrimethylsilane. The reactionis mediated by 0.3–1.0 equiv. of titanium tetrachlor-ide (TiCl4) at room temperature and leads in a multi-step, one-pot reaction to quaternary triallylmethanederivatives 5. The most efficient ester possessed twoortho-methoxy substituents on the phenol ring. Mo-

lecular modelling revealed the ability of this com-pound to form a bidentate titanium complex, thusimproving the steric accessibility of the ester carbon-yl to nucleophilic attack.

Keywords: allylation; allylsilanes; esters; Lewisacids; triallylmethanes

Introduction

Allyl substituents are versatile groups that can bereadily transformed by hydroboration, hydrosilyla-tion, hydrocyanation, hydroformylation, metathesis,epoxidation or aziridination into multiple functionalgroups, some of them in an enantioselective manner.Hence, efficient methods leading to polyallyl com-pounds are of interest not only as building blocks forthe introduction of polyfunctional groups but also inthe synthesis of hyperbranched polymers and den-drimers.[1]

Carboxylic esters are readily available starting ma-terials that could lead to triallylated products. We setas a desirable goal a one-pot, domino conversion ofcarboxylic esters 1 to quaternary triallylmethanes 5(Scheme 1), by means of a non-metallic allylsilane 2,using the same Lewis acid in all three steps. Allylsi-lanes are mild, environmentally friendly reagents andsuch a multi-step, atom-efficient process would alsoreduce waste by minimizing the volume of solvents.

Of the three steps in Scheme 1, the second one(3!4) should proceed readily since it is an exampleof the facile Sakurai–Hosomi reaction[2] (Scheme 2) inwhich aldehydes or ketones 6 undergo nucleophilicattack by allylsilanes in the presence of Lewis acidsleading to homoallyl alcohols 7.

Regarding the first step in Scheme 1, allylsilanesgenerally do not react with esters. But carboxylicesters can be doubly allylated with metal allyl deriva-tives[3] of Mg, Al, Zn, Sm and the reaction stops at

the diallyl alcohol stage. Recently, Batey et al.[4]

found that environmentally friendly non-metallic allyltrifluoroborates (4 equiv.) were effective in the allyla-tion of nitriles, proceeding to diallylamines; in thecase of para-methoxycarbonylbenzonitrile the estergroup was not affected. No one-step triallylation ofesters has so far been reported.

Scheme 1. Proposed triallylation of esters using allylsilane 2and a Lewis acid.

Scheme 2. Allylation of ketons or aldehydes using allylsilane2 and a Lewis acid.

Adv. Synth. Catal. 2014, 356, 2661 – 2670 � 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2661

FULL PAPERS

Although on first glance, the third step in Scheme 1appears problematic, recent studies have shown thatactivated alcohols 8 (mainly benzyl or some tertiary)can be converted to allyl derivatives 9 (Scheme 3) byallylsilanes using a variety of Lewis acids based onB,[5] In,[6] Bi,[7] Fe,[8] Al,[9] Ca,[10] Zr,[11] Re,[12] Rh,[13] aswell as Brønsted acids such as Montmorillonites[14]

and PMA (phosphomolybdic acid),[15] either in cata-lytic or stoichiometric amounts. Recently, we foundthat TiCl4 in dichloromethane (DCM) is more effi-cient than most Lewis acids and promotes, within mi-nutes, the allylation of benzyl, allyl, as well as of sometertiary alcohols at room temperature.[16]

Results and Discussion

The first attempts to carry out Scheme 1 were disap-pointing. In the event, no triallyl product 5 was de-tected in the reaction of 3.1 equiv. of allyltrimethylsi-lane 2 in the presence of TiCl4 (1–2 equiv.) at roomtemperature within 2 h with para-nitrophenyl ben-zoate 1a and meta-nitrophenyl benzoate 1b, each pos-sessing a good nitrophenolate leaving group. The firstpromising result was isolation of ca. 15% of 5 onheating of 1a at reflux for 2 h, though 1b did notafford 5 on heating.

To our delight, ortho-nitrophenyl benzoate 1c inthe presence of 1 equiv. of TiCl4 at room temperaturefurnished 5 within 10 min. in 58% yield, after chroma-tography. Other Lewis acids, [BF3, SbCl5, FeCl3, InCl3,BiBr3, SnCl2, Ti ACHTUNGTRENNUNG(O-i-Pr)4], or HOTf were ineffective,except for AlCl3, which led to 15% of 5 after 0.5 h(Table 1).

On the assumption that the positive effect observedwith 1c may be due to additional coordination of theortho nitro function with the TiCl4 oxophile,[17] wechose several esters to study the scope of the reaction(see Table 2). Simple phenyl benzoate 1d requires2 equiv. of TiCl4 and 1 h to give compound 5 in lowyield. The reaction with ortho-chlorophenyl benzoate1e did not lead to 5 at room temperature within 2 hbut heating at reflux yielded 5 in good yield, while2,4-dinitrophenyl benzoate 1i, led to 5 (40%) at roomtemperature within 30 min. Indeed, ortho-methoxy-phenyl benzoate 1f was more efficient than para-me-thoxyphenyl benzoate 1g in providing 5 (55%, in30 min vs. 30%, in 60 min)[18] but even ortho-methylbenzoate 1h gave the triallylated product in reasona-ble yield.

We have further extended this protocol to the reac-tion of other ortho substituted phenyl esters. Thus,pentafluorophenyl benzoate 1n, possessing not onlyortho Fs but also a good leaving group, reactedsmoothly to produce 5 in 70% yield within 1 h. Themost efficient substrate by far proved to be 2,6-dime-thoxyphenyl benzoate 1j, which afforded 5 in 83%yield within 2 min at room temperature. In anotheraromatic ester example, 2,6-dimethoxyphenyl ester10a also reacted faster and gave triallyl product 17 inbetter yield (30 min, 65%) than the correspondingphenyl ester 10b (120 min, 35%). In many subsequentcases we used 2,6-dimethoxyphenyl esters. Thus, ester11a gave triallyl product 18 in good yield. However,even 2,6-dimethylphenyl benzoate 1k, led to 5 in 49%yield after 30 min and more sterically hindered 2,6-di-alkylated phenyl esters (1l and 1m) likewise under-went triallylation in good yields, indicating that steric

Scheme 3. Allylation of activated alcohols using Lewis acid.

Table 1. Formation of 5 by reaction of 1c with 2 in the pres-ence of different Lewis acids.

[a] Additional time did not improve the yields.[b] Isolated yields after purification.[c] No triallylated prodcut was formed.

2662 asc.wiley-vch.de � 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2014, 356, 2661 – 2670

FULL PAPERSChenna Kesava Reddy Bandi et al.

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Table 2. Reactions of esters with allyltrimethylsilane and TiCl4 to form triallylmethanes.[a]

Adv. Synth. Catal. 2014, 356, 2661 – 2670 � 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim asc.wiley-vch.de 2663

FULL PAPERS The First Allylation of Esters by an Allylsilane: One-Pot Domino Synthesis


Table 2. (Continued)




effects in the phenol portion of the ester play onlya minor role.[19]

After successfully optimizing the conditions for thesynthesis of triallylmethanes on phenyl esters, we ex-amined the heterocyclic system 12. Gratifyingly, thereaction of 12a, 12b with allyltrimethylsilane 2 fur-nished the corresponding triallylated product 19 ingood yields (50, 40%). Finally, the versatility of thereaction was explored with substrates having twoester groups (13a, 14a, 15a). Both para- and meta-di-ACHTUNGTRENNUNGsubstituted esters (13a, 14a) gave triallylated methaneproducts 20, 21 in good yields (55, 50%), while 15agave diallylated lactone 22 in moderate yield (30%),as expected due to neighbouring group interaction.TiCl4 proved effective in the one-pot triallylation ofbenzoate esters not only of phenols, but also of alco-hols (e.g., 1o, 1p) at room temperature in reasonableyield. During the reaction of 1c–n, phenolate is elimi-nated and therefore phenol esters give better yieldsthan alcohol esters. Furthermore, we extended ourprotocol to aliphatic ester 16a, which gave only dially-lated alcohol 23 as a major product (50%, requiring2 h). This is not surprising, since further allylationmost often requires activated alcohols.

TiCl4, a good oxophile, can coordinate with an estercarbonyl,[20] enhancing its positive character and facili-tating the first step in Scheme 1, nucleophilic attackby the allylsilane 2. The second and third steps in thecascade (Scheme 1) are reactions which normally takeplace within a few minutes at room temperature,keeping in mind that aromatic esters will be preferredsubstrates since they promote the third step inScheme 1. Indeed the most reactive examples(Table 2) were aromatic esters. In the allylation ofphenolate esters, an ortho substituent (OMe, NO2) ca-pable of coordination with TiCl4 has a beneficialeffect with the di-ortho-methoxy ester 1j being themost reactive.

After the first step in the ester allylation cascade inwhich the phenolate is lost, identical chemical struc-tures are the reaction participants in both second andthird step allylations of Scheme 1 for all substrates 1.In this light, the first step involving TiCl4 complexa-tion should be rate-determining. To better understandthe impact of molecular structure on the TiCl4-pro-moted reaction of aryl esters 1 with allylsilane 2, wefocused on the initial stage of this multi-step transfor-mation and performed theoretical modelling for

Table 2. (Continued)

[a] Standard reaction conditions: ester (1.0 mmol), allyltrimethylsilane 2 (3.1 mmol), TiCl4 (1.0 M in CH2Cl2,1 mmol), and CH2Cl2 (4 mL) at 25 8C under an inert atmosphere (Ar).

[b] Longer reaction time did not improve the yield.[c] Isolated yields after purification.[d] While the reaction of 1e at reflux temperature gave 5 in good yield (1a gave 15% of 5), no improvement in

yield was observed for the reactions 1b, 1f, 1g under refluxing conditions even after 2–3 h.[e] No product was formed and starting material was recovered.




esters 1a, 1c, 1d, 1f, 1h, 1j, 1k, 1n, and 11a, as well asfor 1:1 and 1:2 ester:TiCl4 complexes.[21] These com-plexes have been computationally located by usingDFT calculations with modelling dichloromethane so-lution (see Experimental Section and the SupportingInformation).

The computationally located 1:1 ester-TiCl4 com-plexes have different chemical structures, dependingon the presence of functional groups. MonodentateC=O–TiCl4 complexes 1aTi, 1cTi, 1dTi, 1fTi, 1hTi, 1jTi,1kTi, 1nTi, and 11aTi have been located for both non-functionalized esters 1d, 1h, 1k, and for esters 1a, 1c,1f, 1j, 1n, 11a with a heteroatom-bearing substituent(see Figure 1 for 1jTi and the Supporting Informationfor others).[22] Methoxy-substituted phenyl esters 1fTi,1jTi, and 11a provide additional complexes; they aremonodentate MeO-liganded complexes 1fTi�OMe, 1jTi�

OMe, and 11aTi�OMe (chemically isomeric to 1fTi, 1jTi and11a, respectively; Figure 1 and the Supporting Infor-mation), as well as bis Ti complexes 1j2Ti, 1f2Ti�2O and1j2Ti�2O (Figure 1 and Supporting Information). In ad-dition we found bidentate Ti complexes 1fTi�2O, 1jTi�2O

and 11aTi�2O (Figure 1 and the Supporting Informa-tion). Similarly, our calculations have located NO2-li-ganded Ti complexes 1aTi�ON and 1cTi�ON for function-alized esters 1a and 1c, respectively (Figure 1a in theSupporting Information). Energy calculations per-formed at the MP2/6-31+G ACHTUNGTRENNUNG(d,p) level show thatMeO�TiCl4 complexes are slightly more stable thanthe C=O�TiCl4 ones, while the latter have a signifi-cantly higher stability than the NO2�TiCl4 com-plexes.[22]

Molecular geometries of the modelled Ti complexesindicate that the complexes, in which the carbonyloxygen and the ether oxygen both chelate the Tiatom (cf. 1jTi�2O) are more reactive in the ester allyla-tion than other Ti complexes. In the monodentate C=O�TiCl4 complexes the carbonyl carbon is severelyshielded from being attacked by a nucleophile. Boththe OPh ring and Ti�Cl fragments are exposed near-orthogonally to the C=CH2 plane of the approachingallylsilane molecule (Figure 2). By turning the O�Phring by ~308 and shifting the TiCl4 molecule from theO�Ph ring plane, chelation of the Ti atom in biden-date complexes 1fTi�2O, 1jTi�2O and 11aTi�2O opens onestereoface of the carbonyl fragment. This striking dif-ference in steric crowding makes evident that thesechelates (and not their monodentate chemical iso-mers) are the Ti complexes which undergo the firstester allylation. This conclusion successfully explainsthe observed higher reactivity (see above) of phenylesters bearing ortho-methoxy substituents that are ca-pable of complexing TiCl4. This also explains themuch better yield of 5 from ortho-nitro ester 1c thanfrom the para isomer 1a (Table 2). CalculatedHOMOs and LUMOs for the modelled esters andtheir complexes with TiCl4 provide further qualitative

understanding of the structure-reactivity relationshipfor this allylation (Supporting Information).

Methoxy-substituted esters 1f, 1j, and 11a are capa-ble of chemically differently complexing TiCl4

(Figure 1 and Supporting Information). Chelation ofTi both by the C=O and the ortho-substituent signifi-cantly diminishes steric hindrances for a nucleophilicattack, as is shown for the ortho-MeO structures 1fTi�

2O and 1jTi�2O (Figure 2). Therefore these bidentatecomplexes are the reactive electrophilic substrates inthe first allylation (Scheme 4). In orbital terms, this

Figure 1. Optimized molecular geometries for complexes1jTi, 1jTi�OMe, 1j2Ti�2O, 1fTi�2O and 1jTi�2O.




chelation is provided by interaction of the LUMO (lo-calized on the TiCl4 fragment) and the molecular or-bital associated with a higher energy lone electronpair of the carbonyl or ether oxygen (Figure 1a in theSupporting Information).[23]

The energy gap DEL�H between the LUMO andthis molecular orbital for complexes 1fTi, 1jTi and11aTi is 0.038523, 0.033990, and 0.036313 hartrees, re-spectively. Similar values of DEL�H are much larger

for corresponding alternative monodentate Ti com-plexes 1fTi�OMe, 1jTi�OMe, and 1j2Ti, respectively(Scheme 4 and Supporting Information). Thus, Ti spe-cies 1fTi, 1jTi and 11aTi are favoured precursors of thecorresponding reactive complexes 1fTi�2O, 1jTi�2O and11aTi�2O.

The exceptionally high reactivity of ester 1j(Table 1a in the Supporting Information) becomes ap-parent from the LUMO�MO-nO energy gap which issignificantly lower for dimethoxy structure 1jTi com-pared to monomethoxy and trimethoxy analogues 1fTi

and 11aTi.[24]

Conclusions

In summary, we have developed for the first timea synthetic strategy in which aromatic esters are con-verted to triallylated products by means of allyltrime-thylsilane and TiCl4 in an efficient and rapid cascadereaction at room temperature. The successful forma-tion of bis triallylated products 19 and 20 may be val-uable for the synthesis of hyperbranched polymersand dendrimers. Molecular modelling studies indicatethat coordination of ortho-methoxy groups to TiCl4

relieves steric congestion around the carbonyl groupof phenolate esters facilitating allylation.

Experimental Section

General Methods

Unless otherwise noted, chemicals were purchased fromcommercial suppliers at the highest purity grade availableand were used without further purification. Solvents weredistilled by standard methods. Thin layer chromatographywas performed on Merck pre-coated 0.25 mm silica gelplates (60F-254) using UV light as visualizing agent and/oriodine as developing agent. Neutral alumina (Fluka; pH/:7.0+ /- 0.5) was used for column chromatography.

Melting points were recorded on an uncorrected PerfitMelting Point instrument. IR spectra were recorded on anFT-IR spectrometer and expressed as wave numbers (cm�1).1H and 13C NMR spectra were recorded on a Bruker(300 MHz and 75 MHz) spectrometer. Spectra were refer-enced internally to the residual proton resonance in CDCl3

(d=7.26 ppm) or with tetramethylsilane (TMS, d=0.00 ppm) as the internal standard. Chemical shifts (d) werereported as part per million (ppm) in d scale downfield fromTMS. 13C NMR spectra were referenced to CDCl3 (d=77.0 ppm, the middle peak). Coupling constants were ex-pressed in Hz. The following abbreviations were used to ex-plain the multiplicities: s= singlet, d=doublet, t= triplet,dt=doublet of triplet, m=multiplet, br=broad. High reso-lution mass spectra (HR-MS) were obtained on a BrukermicrOTOF�-Q II mass spectrometer (ESI-MS).

Ester compounds (1a–1p, 10a, 10b, 11a, 12a, 12b, 13a, 14a,15a, 16a) were prepared using literature procedures, and for

Scheme 4. Formation of bidendate Ti complexes 1fTi�2O, 1jTi�

2O, and 1jTi�2O from monodentate C=O�TiCl4 and MeO�TiCl4 complexes. Grey background indicates favoured mon-odentate precursors, MO-nO refers to the highest occupiedmolecular orbital for which localization includes the Oatoms.

Figure 2. Steric hindrances (indicated by dotted arcs) in thenucleophilic attack of the allylsilane (shown schematicallyon the right of each structure) on monodentate Ti com-plexes 1dTi, 1fTi, 1hTi, 1jTi, 1kTi and 1nTi, as well as bidendatecomplexes Ti 1fTi�2O and 1jTi�2O. In the optimized moleculargeometries (shown) of the Ti complexes, bent arrows pointout the carbon atom of the carbonyl unit.




known compounds data have been compared with the re-ported data. Characterization data for new compounds isgiven below.

Calculations

Non-empirical calculations have been performed usingGaussian09 package. PCM model (an implicit model of sol-vation) implemented in this package has been used for mod-elling dichloronmethane solution. The molecular geometryof all the modelled Ti complexes has been optimized by em-ploying DFT calculations at the MPWLYPM1/cc-pVDZlevel; for complexes 1aTi, 1aTi�ON, 1cTi, 1cTi�ON, 1jTi, and 1jTi�

OMe, also by using ab initio calculations at the MP2/6–31 +G-ACHTUNGTRENNUNG(d,p) level. In cases of difficult convergence, successful ge-ometry optimization has been achieved by combining (i)Newton–Raphson method, (ii) the use of Cartesian coordi-nates, (iii) computation of force constants at the first point,and (iv) involvement of the quadratically convergent SCFprocedure [in Gaussian terms, by combining commandsOpt= (Newton, Cartesian, CalcFc) and SCF=QC (orSCF =XQC, if unsuccessful)]. For initial structures of Ticomplexes, see the Supporting Information.

General Procedure for the Synthesis of Esters:[25]

To an ice-cold solution of phenol (11 mmol), triethylamine(11 mmol) in DCM (10 mL) was added dropwise an acylchloride (10 mmol). After stirring at room temperature for30 min and washing with 1 M HCl solution (5 �2 mL), thecombined organic layers were dried on anhydrous MgSO4.The ester product was recrystallized from ethanol-hexane.

2,6-Dimethoxyphenyl 4-methylbenzoate (10a, Table 2):Yield: 2.4 g (88%); white solid; mp 99–101 8C; 1H NMR(300 MHz, CDCl3): d=2.45 (s, 3 H), 3.79 (s, 6 H), 6.62 (d,J=8.5 Hz, 2 H), 7.16 (t, J=8.5 Hz, 1 H), 7.29 (d, J= 8.1 Hz,2 H), 8.16 (d, J= 8.3 Hz, 2 H); 13C NMR (75 MHz, CDCl3):d= 22.0, 56.4, 105.2, 119.3, 126.5, 126.9, 129.4, 130.0, 130.7,144.4, 152.9, 164.8; MS: m/z (rel intensity) =295 (100) [M+Na]+.

2,6-Dimethoxyphenyl 4-methoxybenzoate (11a, Table 2):Yield: 2.2 g (76%); white solid; mp 110–112 8C; 1H NMR(300 MHz, CDCl3): d=3.79 (s, 6 H), 3.87 (s, 3 H), 6.66 (d,J=8.5 Hz, 2 H), 6.99 (d, J=8.7 Hz, 2 H), 7.15 (t, J= 8.5 Hz,1 H), 8.18 (d, J= 8.8 Hz, 2 H); 13C NMR (75 MHz, CDCl3):d= 55.7, 56.4, 105.1, 113.9, 119.3, 122.0, 126.4, 132.7, 152.9,164.0; MS: m/z (rel intensity) =311 (100) [M +Na]+.

2,6-Dimethoxyphenyl thiophene-2-carboxylate (12b,Table 2): Yield: 2.1 g (79%); white solid; mp 112–114 8C;1H NMR (300 MHz, CDCl3): d= 3.80 (s, 6 H), 6.64 (d, J=8.4 Hz, 2 H), 7.17–7.19 (m, 2 H), 7.64 (dd, J=3.8, 1.1 Hz,1 H), 8.01 (dd, J=2.6, 1.1 Hz, 1 H); 13C NMR (75 MHz,CDCl3): d= 56.4, 105.2, 126.7, 128.1, 128.8, 132.9, 133.4,134.9, 152.9, 160.2; MS, m/z (rel intensity)= 265 (50) [M+H]+, 193 (100).

Bis(2,6-dimethoxyphenyl) terephthalate (13a, Table 2):Yield: 3.8 g (86%); white solid; mp 205–207 8C; 1H NMR(300 MHz, DMSO-d6): d= 3.83 (s, 12 H), 6.87 (d, J= 8.4 Hz,4 H), 7.31 (t, J=8.7 Hz, 2 H), 8.37 (s, 4 H); 13C NMR(75 MHz, DMSO-d6): d=57.3, 106.3, 128.0, 129.0, 131.0,131.2, 131.6, 134.2, 153.1, 164.1; MS: m/z (rel intensity)= 461(100) [M +Na]+.

Bis(2,6-dimethoxyphenyl) isophthalate (14a, Table 2):Yield: 3.65 g (83%); white solid; mp 154–156 8C; 1H NMR(300 MHz, CDCl3): d=3.81 (s, 12 H), 6.67 (d, J= 8.4 Hz,4 H), 7.18 (t, J= 8.4 Hz, 2 H), 7.65 (t, J=7.8 Hz 1 H), 8.49(dd, J= 7.8, 6.8 Hz, 2 H), 9.10 (m, 1 H); 13C NMR (75 MHz,CDCl3): d= 56.4, 105. 2, 119.3, 126.7, 129.0, 130.3, 132.6,135.3, 147.5, 152.7, 164.0; MS: m/z (rel intensity)= 461 (100)[M+Na]+.

Bis(2,6-dimethoxyphenyl) phthalate (15a, Table 2): Yield:3.2 g (73%); white solid; mp 159–161 8C; 1H NMR(300 MHz, CDCl3): d=3.75 (s, 12 H), 6.61 (d, J= 8.4 Hz,4 H), 7.12 (t, J=8.4 Hz, 2 H), 7.62 (dd, J= 9.0, 5.7 Hz, 2 H),8.10 (dd, J=9.0, 5.7 Hz, 2 H); 13C NMR (75 MHz, CDCl3):d= 56.4, 105.3, 119.3, 126.5, 129.3, 130.2, 131.5, 132.1, 152.9,164.6; MS: m/z (rel intensity) =461 (100) [M +Na]+.

2,6-Dimethoxyphenyl hexanoate (16a, Table 2): Yield:2.2 g (87%); yellow liquid; 1H NMR (300 MHz, CDCl3): d=0.9 (t, J= 7.1 Hz, 3 H), 1.32–1.49 (m, 4 H), 1.80 (pent, J=7.4 Hz, 2 H), 2.62 (t, J= 7.4 Hz, 2 H), 3.88 (s, 6 H), 6.60 (dd,J=6.3, 1.8 Hz, 2 H), 7.12 (m, 1 H); 13C NMR (75 MHz,CDCl3): d= 14.2, 22.6, 25.0, 31.4, 34.0, 56.3, 105.1, 126.3,129.1, 152.6, 171.8; MS: m/z (rel intensity) =252 (100) [M]+.

General Procedure for the Preparation ofTriallylmethane Products

To a stirred solution of ester (1 mmol) in dry DCM (4 mL),were added TiCl4 (1.0 M sol.ution in DCM, 1 mL) and allyl-trimethylsilane (3.1 mmol) under an inert atmosphere andkept at 20 8C for the stipulated time (see Table 2). Longerreaction times did not improve the yield. After completionof the reaction (TLC), the excess of solvent was removed byrota-vapor and the residue was purified by neutral aluminacolumn chromatography, using ethyl acetate (1–2%) in hex-anes as an eluent to give the triallylated products in good toexcellent yields.

(4-Allylhepta-1,6-dien-4-yl)benzene (5, Table 2):[26]

1H NMR (300 MHz, CDCl3): d=2.62 (d, J= 7.0 Hz, 6 H),5.12–5.24 (m, 6 H), 5.64–5.80 (m, 3 H), 7.30–7.38 (m, 1 H),7.47 (d, J=4.7 Hz, 4 H); 13C NMR (75 MHz, CDCl3): d=42.1, 43.5, 117.8, 126.0, 126.9, 128.3, 134.8, 145.9; MS (EI,70 eV): m/z (%)= 212 (M + , 23), 171 (86); HR-MS (EI +):m/z= 212.1526, calcd. for C16H20 [M]+: 212.1565.

1-(4-Allylhepta-1,6-dien-4-yl)-4-methylbenzene (17,Table 2): 1H NMR (300 MHz, CDCl3): d=2.33 (s, 3 H), 2.45(d, J=7.2 Hz, 6 H), 4.98–5.04 (m, 6 H), 5.58–5.70 (m, 3 H),7.15 (d, J= 8.1 Hz, 2 H), 7.20 (d, J=8.3 Hz, 2 H); 13C NMR(75 MHz, CDCl3): d= 21.2, 42.2, 43.2, 117.8, 126.8, 129.0,135.0, 135.4, 142.9.

1-(4-Allylhepta-1,6-dien-4-yl)-4-methoxybenzene (18,Table 2):[1e] 1H NMR (300 MHz, CDCl3): d=2.44 (d, J=7.2 Hz, 6 H), 3.81 (s, 3 H), 4.98–5.08 (m, 6 H), 5.50–5.70 (m,3 H), 6.87 (dd, J=8.9, 6.6 Hz, 2 H), 7.23 (dd, J=8.9, 6.7 Hz,2 H); 13C NMR (75 MHz, CDCl3): d=42.2, 42.9, 55.4, 113.6,113.8, 117.8, 118.6, 127.9, 134.9, 138.0, 157.7.

2-(4-Allylhepta-1,6-dien-4-yl)thiophene (19, Table 2):1H NMR (300 MHz, CDCl3): d=2.43 (d, J= 7.4 Hz, 6 H),5.00–5.10 (m, 6 H), 5.60–5.67 (m, 3 H), 6.79 (d, J= 3.4 Hz,1 H), 6.93 (m, 1 H), 7.18 (d, J=5.1 Hz, 1 H); 13C NMR(75 MHz, CDCl3): d= 43.3, 43.4, 117.9, 123.0, 123.5, 126.2,133.9, 152.0; MS (EI, 70 eV): m/z (%)= 248 (M+ , 27), 177(100).




1,4-Bis(4-allylhepta-1,6-dien-4-yl)benzene (20, Table 2):[1e]

1H NMR (300 MHz, CDCl3): d=2.43 (d, J=7.2 Hz, 12 H),4.96–5.01 (m, 12 H), 5.47–5.60 (m, 6 H), 7.23 (s, 4 H).13C NMR (75 MHz, CDCl3): d=42.1, 43.3, 117.8, 126.6,134.9, 135.0, 143.2.

1,3-Bis(4-allylhepta-1,6-dien-4-yl)benzene (21, Table 2):1H NMR (300 MHz, CDCl3): d=2.42 (d, J=7.0 Hz, 12 H),4.94–5.00 (m, 12 H), 5.45–5.57 (m, 6 H), 7.07–7.10 (m, 2 H),7.20–7.23 (m, 2 H); 13C NMR (75 MHz, CDCl3): d 42.2, 43.8,117.8, 124.3, 125.7, 127.9, 134.9, 145.4;

3,3-Diallylisobenzofuran-1(3H)-one (22, Table 2):[4]

1H NMR (300 MHz, CDCl3): d=2.61–2.78 (m, 4 H), 5.01 (s,2 H), 5.05–5.07 (m, 2 H), 5.46–5.60 (m, 2 H), 7.36 (d, J=7.7 Hz, 1 H), 7.48 (t, J= 7.9 Hz, 1 H), 7.64 (td, J=7.7, 7.3 Hz,1 H), 7.84 (d, J= 7.6 Hz, 1 H); 13C NMR (75 MHz, CDCl3):d= 42.9, 88.5, 120.6, 121.8, 125.9, 127.1, 129.3, 130.9, 134.1,151.8, 170.1.

4-Allyloct-1-en-4-ol (23, Table 2):[27] 1H NMR (300 MHz,CDCl3): d=0.90 (t, J=6.7 Hz, 3 H), 1.27–1.46 (m, 8 H), 2.21(d, J=7.5 Hz, 4 H), 5.08–5.14 (m, 4 H), 5.77–5.90 (m, 2 H);13C NMR (75 MHz, CDCl3): d= 14.3, 22.9, 32.6, 39.4, 44.0,73.8, 118.9, 134.1.

Acknowledgements

We are grateful to the India-Israel Fund for a fellowship toC.K.R.B. and to the Marcus Center for Medicinal and Phar-maceutical Chemistry at Bar-Ilan University for partial sup-port of this research.

References

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[18] Except in the case of 1e, heating under reflux tempera-ture did not lead to significant improvement in theyield of 5.

[19] The reactivity of sterically encumbered 2,6-disubstitut-ed phenolates may be due in part to decompression onloss of the phenolate after initial attack of the allylsi-lane on the ester.

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[22] Modelled monodentate complexes have trigonal bipyr-amidal geometry of the Ti-centered molecular unit, andthe oxygen ligand occupies an apical position. O�Tibonds between the carbonyl oxygen of esters with TiCl4

are shorter than such bonds between the ether or nitrogroup oxygen with this Lewis acid. The calculatedlength of the C=O�TiCl4 bond in the modelled com-plexes is within the range of 0.209–0.213 nm, while thelength of the O�Ti bond (apical) is 0.237, 0.224 and0.227 nm in the MeO�TiCl4 complex 1jTi�OMe and in theNO2-liganded Ti complexes 1aTi�ON and 1cTi�ON, respec-tively. The O�Ti (apical) bond in bis-Ti complexes1f2Ti�2O, 1j2Ti�2O and 1j2Ti is elongated to a length of0.247 to 0.249 nm. Bidentate complexes 1fTi�2O and 1jTi�

2O have the Ti atom of somewhat distorted bipyramidalsquare geometry with both oxygen ligands occupyingequatorial positions. Values of the length of the O�Tibond (equatorial) from the carboxyl fragment are in

the 0.207–0.209 nm range, while the range of the lengthof the O�Ti bond (equatorial) from the MeO fragmentis 0.245–0.247 nm. The C=O�-TiCl4 complex 1jTi islower in energy by 0.9 kcal mol�1 than its chemicalisomer 1jTi�OMe with an MeO�TiCl4 bond. The NO2�TiCl4 complex 1cTi�ON has a 4.2 kcal mol�1 higher energythan the related C=O�TiCl4 complex 1cTi (SupportingInformation).

[23] This molecular orbital is an analogue of the HOMOfor simplest AlkC(=O)X or AlkOAlk compounds(non-bonding O-centered orbital nO). It interacts withthe TiCl4-localized LUMO of the monodentate com-plex when liganding the Ti atom to the second oxygen.

[24] However, the DEL�H differences for 1fTi and 11aTi

(Scheme 4) do not explain the relative reactivity of thecorresponding esters (Table 2). Since the frontier orbi-tal approximation does not take into account steric fac-tors that appear when reacting molecules or molecularfragments draw closer, we also considered structure-specific details of molecular geometry. The distance be-tween the Ti-liganding oxygens is quite similar in che-lates 1fTi�2O and 11aTi�2O (0.275 and 0.279 nm, respec-tively). However, the shorter interatomic O�O non-bonging distance in complex 1fTi (0.321 nm) vs. that in11aTi (0.362 nm) facilitates intramolecular chelation andleads to more efficient conversion of 1fTi vs. 11aTi intothe related reactive complexes 1fTi�2O and 11aTi�2O.

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[27] a) J. Barluenga, C. Rubiera, J. R. Fern�ndez, J. Florez,M. Yus, Synthesis 1987, 819–821; b) R. L. Snowden,S. M. Linder, B. L. Muller, K. H. Schulte-Elte, Helv.Chim. Acta 1987, 70, 1858–1878.




the first allylation of esters by an allylsilane: one-pot domino synthesis of triallylmethane...

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