Allylsilanes with enones

Apparently the Lewis acid induced and the fluoride-induced reactions of allylsilanes with enones follow different pathways. The perpendicular approach of the nucleophilic allylsilane... 

Both inter- and intramolecular reactions of allylsilanes with enones have been reported. 1,4-Addition of allylsilane to the conjugated enone shown below permits direct introduction of an angular allyl group to a bicyclic enone. 

Kuroda, C., Nogami, H., Ohnishi, Y., Kimura, Y.. and Satoh. J.Y. Stereochemistry of Lewis acid and fluoride promoted intramolecular cychzation of P-(alkoxycarbonyl)allylsilane with enones. Synthesis of bicyclo[4.3.0]nonanes. Tetrahedron. 53, 839, 1997. 

Since allylsilane can be considered as a very soft nucleophile because of the involvement of o-7i conjugation between the -electrons of the double bond and the o-electrons in the carbon-silicon bond, the addition of allylsilanes to ,/3-unsaturated enone moiety occurs exclusively via 1,4-addition19,20. A typical Sakurai-Hosomi reaction is illustrated in the reaction of allylsilane 66 with enone 67 in the presence of TiCU to give 68 which is used for the synthesis of a cyclic enediyne (equation 45)108. A similar reaction has been used for the synthesis of ewf-herbasolide 70 from enone 69 (equation 46)109. Prenylsilane undergoes 1,4-addition with squaric acid chloride 71 followed by dechlorosilylation to give 72 as the predominant product (equation 47). Interestingly, other simple allylsilanes react in a 1,2-addition fashion to yield 73110. 

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 ... 

The [3 + 2] reaction of an allylsilane with an enone was proposed to proceed via a regiospecific electrophilic substitution (cf 80) of the enone at C-3 of the allylsilane followed by a cationic 1,2-silyl migration (equation 57). At the yyw-clinal transition state (81), the carbonyl group of the unsaturated ketone was assumed to occupy an endo orientation in relation to the allylsilane142. The transition state was thought to be favorable due to minimization of the charge separation and to possible secondary orbital stabilization. 

In the presence of Me2AlCl, isocyclic allylsilane 28 adds to 3-butyn-2-one to afford an ct-enone bearing an allylsilane moiety (Equation (38)).1S1,1Sla In contrast, the ZnI2-promoted ene reaction of an acyclic /3-substituted allylsilane with an a-ynone forms a vinylsilane product exclusively.152... 

The reaction of homochiral allylsilanes with a-enones and a-enals is very valuable for the asymmetric synthesis of multisubstituted cyclopentanes (Equation (40)).161,162 The [3 + 2]-cycloaddition of allylsilanes is applicable to />-quinones163 and />-quinoneimines.164 3-Butyn-2-one undergoes a double cycloaddition with an excess amount of allyltriisopropylsilane to give a bicyclo[3.3.0]octane in good yield (Equation (41)).165... 

Under Lewis add catalysis, the reaction of allylsilanes takes place easily with a-enones but not with a,P-unsaturated esters [162]. Because disappointing results were obtained in reactions of allylmetals with a,P-unsaturated carbonyl compounds, reactions of allylsilanes with electrophiles bearing chiral auxiliaries have been examined. Schultz and Lee [1435] performed the T1CI4 catalyzed addition of trimethylallylsilane to compound 7.67 at -78°C. After treatment with methylhy-droxylamine in acidic media, the 1,4-adduct 7.80 was obtained with high ee (Figure 7.56). Under similar conditions, N-enoyloxazolidinone 7.68 (R = Ph) or sultam... 

Conjugate addition of allylsilanes to enones results in regiospe-cific introduction of the allyl group (eq 34). The reaction can be intramolecular (eq 35). TiCU or SnCU activates nitro alkenes for Michael addition with silyl enol ethers or ketene silyl acetals. The silyl nitronate product is hydrolyzed to a 1,4-diketone or -y-keto ester (eq 36). ... 

CONJUGATE ALLYLATION OF a,g-ENONES WITH ALLYLSILANES PROMOTED BY TITANIUM TETRACHLORIDE Conditions... 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

So far, there is no conclusive evidence that a free allyl carbanion is generated from allylsilanes under fluoride ion catalysis. A hypervalent silyl anion, with the silicon still bonded to the allylic moiety, accounts equally well for the results obtained. Based on a variety of experimental results, it is in fact more likely that a nonbasic hypervalent silyl anion is involved rather than the basic free allyl carbanion first postulated14-23. When allylsilanes are treated with fluoride in the presence of enones. 1,4-addition takes place along with some 1,2-addition13. 

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... 

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... 

Both silyl enolates and allylsilanes are excellent nucleophiles for alkylation by other stabilized carbocations such as the tertiary alkyl cations 111 or 112 (Scheme 2.42). Similarly, Michael-like additions, for example, the coupling of 113 with silyl ketene acetal 114, can be also achieved.Owing to the high electrophilicty of the enone system, this reaction proceeds smoothly in polar solvents, even in the absence of Lewis acids. 

The Znl2-promoted reaction provides an a-enone bearing a vinylsilane moiety as a minor product In contrast under similar reaction conditions reaction of allylsilane 141 with an a-ynone forms a vinylsilane product with high regioselectivity [449]. 

The titanium tetrachloride-promoted addition of allyltrimethylsilane to methylcyclohexenones and methylcycloheptenones has been explored (68,69) results are summarized in Eqs. [l]-[6] of Scheme 32. With the exception of 4-substituted cyclohexenones and cycloheptenones, good to excellent facial selection is observed (Eqs. [2], [5], and [6], Scheme 32). The major products obtained are those predicted by axial attack of the nucleophile on the more stable conformer of the acceptor. Although there are some similarities, the results show some significant deviations from the corresponding cuprate additions. Addition to the bicyclic enone 32.1 occurs from the convex face, producing exclusively the cis-fused decalone (Eq. [7], Scheme 32) (5). In this case, the product is formally the result of equatorial attack of the allylsilane on the a,/ -unsaturated ketone. 

Unsaturated acylsilanes have been found to be powerful electrophiles in conjugate allylations with allylsilanes subsequent oxidation leads to carboxylic acids in good yields (Scheme 9). The method is remarkably tolerant of steric constraints, in contrast to related anionic Michael additions to enone systems, and should be widely applicable. 

Allyl acetates are readily converted to allylsilanes in good yields, when they are reacted with 0.5 equiv of tris(trimethylsilyl)aluminum etherate and 4-6 mol % of Pd(PPh3)4 in THF at 0-25 °C (Scheme 34).For the reaction with unsynunetrical allyl acetates, the trimethylsilyl group tends to attack the more substituted carbon of the allyUc system under Pd-catalyzed conditions. With 10 mol % of Mo(CO)e (toluene reflux for 2.5 h), on the other hand, the trimethylsilyl group selectively attacks the less substituted carbon as exemplified by the exclusive formation of geranyl(trimethyl)silane in 65% yield. Under the Pd-catalyzed conditions, many functional groups of synthetic importance (e.g., vinyl bromide, acetals, esters, and enones) remain intact. 

The allylation of a carbonyl compound, or equivalent thereof (aldehydes, ketones, acetals, ketals, enones, acid chlorides, epoxides, etc.), performed with an allylsilane 39 promoted by a Lewis acid (TiCl, SnCl, BF3-OEt2, AICI3, EtjAlCl, etc.) is known as Hosomi-Sakurai reaction (Scheme 12.11, Eq. 1) [68, 69]. This reaction was first described in 1976, allowing the synthesis of homoallylic alcohols 43 from aldehydes and ketones 40 [70]. A year later, the authors extended the method to ketals 41, which provide homoallylic ethers 44 (Scheme 12.11, Eq. 2) [71], and to a,p-unsaturated ketones 42 (Scheme 12.11, Eq. 3) [72]. 

We then prepared trienone 2, a substrate with three electrophilic sites (Eq. 5). In addition to the possibility of 1,2-addition, 5 might react with the allylsilane moiety in either 1,4- or 1,6-fashion to annulate a cyclopentane or cycloheptane ring, respectively (cf. 6 and 2). The chemistry of trienone 2 proved intriguing. Treatment of 5 with ethylaluminum dichloridel2 gave the 6-7 fused bicyclic enone in 55% yield, uncontaminated by other products. In contrast, treatment of 5 with fluoride ion produced hydrindanone 2 in 45% yield, accompanied by 5% of a bicyclic tertiary alcohol resulting from 1,2-addition. 

The formation of silane is consistent with a reaction pathway in which the silicon-stabilized cationic intermediate resulting from l,6-ad(fition by the allylsilane undergoes intramolecular alkylation to form a cyclobutane ring. This analysis complements House s observations that signficant quantities of cyclobutyl silane 75 are produced when 22 reacts with an enone and TiCU at elevated temperatures (Eq. 3).ll... 

The generality of these cyclizations caused us to question the necessity of using an allylsilane to achieve cycloheptane annulation. We therefore prepared trienone 26. which lacks a trimethylsilyl moiety. Treatment of 26. with ethylaluminum dichloride at 0 °C gave enone 22 in 45% yield. Enone 22 results from a ring closure which first forms a cycloheptane ring with a tertiary carbonium ion this intermediate then undergoes irreversible intramolecular alkylation. 

Asymmetric Michael addition of optically active perhydro-l,4-oxazepin-5,7-diones, and of thioglycollic acid in the presence of a cinchona alkaloid as catalyst, to a-nitro-olefins yields y-nitrocarboxylic acids and 2-nitrothio ethers, respectively, with reasonable enantiomeric excess. Allylsilanes add to a-nitro-olefins in the presence of aluminium chloride to give unsaturated nitronic acids, which are further transformed in a Nef-type reaction to give y,5-enones (Scheme 36).Nitro-compounds are also converted into the corresponding carbonyl compounds upon treatment with base and MoOs pyHMPA, a new modified Nef reaction. 

Reaction with Carboxylic Acid Derivatives. Reaction of (1) with carboxylic acid derivatives provides silyl ketones (3) (eq 4). The reaction 3ueld is very dependent upon the presence of a-hydrogens in the substrate lower yields are obtained when deprotonation can occur at this center. The reaction occurs with esters, lactones, acid chlorides, and the parent carboxylic acids. The resultant /3-silyl ketones can be desilylated by simple hydrolysis, or used as a substrate in a Peterson alkenation approach to enones. The use of a cerium reagent with the acid chloride has been advocated for the preparation of allylsilanes. ... 

Nncleophilic Addition and Substitution Reactions. Allylsilane (3) has been shown to undergo conjugate addition to enones in the presence of tetra- -butylammonium fluoride (eq 6). The reaction demonstrates high regioselectivity, as no products arising from 1,2-addition to the enone or attack at the /-position of the allylsilane were isolated. Stereoselective C-glycosidation can be effected by reaction of allylsilane (3) with D-mannopyranoside derivatives in the presence of boron trifluoride etherate (eq 7). The a-C-glycoside arises from axial addition to the pyranoside oxonium ion. 

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