Allylsilanes conjugate addition

The required highly carbon-substituted enynes, such as (7) and (8), are conveniently prepared by the Sakurai-Hosomi allylsilane conjugate addition, followed by conversion of methyl ketones into silyl-ated alkynes, as shown in equation (10)."... 

Allylsilanes in which the silyl group is at the more substituted end of the allyl system have been prepared by a reaction sequence involving the conjugate addition of silylcuprates to a, jS-unsat-urated esters followed by reduction and dehydration via selenoxide elimination38. 

Intramolecular conjugate addition of allylsilanes to enones (12, 25). In an extension to the earlier study, Majetich et al.5 have examined the intramolecular addition of allylsilanes to cyclic enones. The course of cyclization depends markedly on the choice of catalyst and on the size of the ring that is formed. 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

Lewis acid-promoted asymmetric conjugate addition of an allylsilane to a series of 8-arylmenthol-derived A -acy I-2.3-di hydro-4-pyri doncs (122) has been reported to lead to 2-allyl-4-piperidones with moderate to high levels of asymmetric induction the highest levels were attained with Ar = 2-naphthyl. The stereochemical course of the reaction was attributed to re-stacking and the method was applied to the asymmetric synthesis of (—)-A-mcthy Icon i i nc.9 5... 

Lewis acid-catalyzed stereoselective addition of crotylsilanes to chiral 74 has been studied in detail111,112. The presence of the chiral auxiliary at C2 (e.g. p-tolylsulfinyl or menthoxy carbonyl group) induces the diastereofacially selective addition of cyclopentenones with crotylsilanes. Thus, ( )-crotylsilane favors the erythro product, whilst (Z)-isomer favors the threo product. High enantioselectivity is observed in both reactions (equation 48). In a similar manner, conjugated addition of allylsilane to 75 proceeds with high efficiency (equation 49)113. Interestingly, the yield and enantiomeric excess of the product is dependent on the amount of TiCL used and the best selectivity... 

The conjugate addition of lithium bis(phenyldimethylsilyl)cuprates to tt./t-unsaUi rated esters forms enolates, which readily react with aldehydes to give 2-substituted 3-silyl esters (equation 129)509. The products are useful as intermediates in the synthesis of allylsilanes and natural products. Yields of this reaction may be significantly increased by... 

This related conjunctive reagent has been used for methylenecyclopentane annelation of a cyclic a,/f-cnonc by conjugate addition of the nucleophilic allylsilane unit of 2 to Ihe cmmc followed by cyclization (equation ) A... 

Conjugate allylation with allyisUanes. This Lewis acid allows conjugate addition of allylsilanes to enones with regiospecific transposition of the allyl group. Acyclic and cyclic enones and even fused cyclic enones react satisfactorily.1 Examples ... 

These results can be explained in terms of an interplay of stereoelectronic and steric factors. Steric factors are evidently more important in the reaction of bulky cuprate clusters than in the Sakurai reaction. Thus stereoelectronic factors predominate in the allylsilane reaction. Similar effects are observed in conjugate additions to substituted cyclohepten-ones. 

Intramolecular Sakurai reaction (7, 371).6 The intramolecular conjugate addition of an allylsilane group to an a,(3-enone can be effected with high stereoselectivity. Thus... 

Hosomi, A., Sakurai, H. Chemistry of organosilicon compounds. 99. Conjugate addition of allylsilanes to a,(3-enones. A New method of stereoselective introduction of the angular allyl group in fused cyclic a,p-enones. J. Am. Chem. Soc. 1977, 99, 1673-1675. 

The Hosomi-Sakurai reaction is a powerful method for conjugate allylation of a,fi-unsaturated ketones [425], In the presence of TiCl4 the allylation occurs smoothly at the y-position of allylsilanes and the / -position of a, -unsaturated ketones. This highly regioselective process has been widely used for introduction of functionalized carbon chains and construction of carbocycles in natural product synthesis [6, 426]. When TBAF is used as catalyst, both conjugate addition and 1,2-addition occur competitively [333]. The fluoride ion-catalyzed procedure is, however, effec-... 

The intramolecular version of the Lewis-acid-promoted conjugate addition of allylsilanes to a,/ -unsaturated ketones (Hosomi-Sakurai reaction) has... 

Even when isomeric mixtures of the allylsilane are used, complete stereochemical control is observed for all the stereocenters established in the conjugate addition. The only breakdown in selectivity in the process occurs with the stereocenters adjacent to the carbonyl carbon, which result from protonation on work-up. The less stable cis-fused decalone is readily converted to the trans-fused isomer by treatment with base. Hence, with two steps, complete control over the relative configuration of four contiguous stereogenic centers is achieved. 

In some instances, particularly when a dependence of the stereochemistry on the double-bond geometry of either the acceptor or donor is observed, it appears likely that the stereochemistry-determining step is the initial conjugate addition. The stereochemical consequences of Lewis-acid-mediated additions of silyl enol ethers (116) and allylsilanes (117,118) have frequently been rationalized by open-extended transition states. Similar pathways seem likely with the Mukaiyama-Michael addition (vide infra) (77,79). 

The conjugate addition of allylsilanes to a,ft unsaturated carbonyl compounds generally proceeds with 1, 4 addition 95 199 (equation 65). Intramolecular reactions of allyl... 

Conjugate allylation of a, enones Titanium(IV) chloride is the most effective activator for conjugate addition of allylsilanes to a,jS-unsaturated ketones. 

Conjugate addition of allylsilanes to a/8-enones is promoted by titanium(iv) chloride. Most significantly an allyl group can be transferred to the bridgehead position in a fused cyclic a/8-enone using this technique (Scheme 78). ... 

C—C Bond Formation using Organosilanes. Under catalysis by TiCU, allylsilanes transfer the allyl group, with rearrangement, to ketones, a/3-unsaturated ketones (conjugate addition), and quinones (initially giving the carbonyl addition product which then further rearranges to the 2-allyl-l,4-hydroquinone). But-3-enyl-silanes react with acid chlorides to yield cyclopropylmethyl ketones [reaction (3)) under similar conditions. 

The Sakurai reaction involves the conjugate addition of an allylsilane to an a, -unsaturated ketone in the presence of a Lewis acid. Suggest a mechanism for the following intramolecular Sakurai reaction ... 

Cyclohexane formation is not restricted to 1,6-addition of an allylsilane to a dienone. Equation 10 contains two examples whereby a lengthy tether linking the reactive functionalities leads to cyclohexane annulation via 1,4-conjugate addition. 

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