Sakurai allylation/addition

TiCl4 is used extensively as a Lewis acid in numerous organic transformations, forming adducts that mediate reactivity. Such reactions include Diels Alder, 54,355 hetero Diels Alder,356 cyclization of olefinic aldehydes,357 Flosomi Sakurai allylic coupling reactions,358 cyclopropanations,359 chal-cogen-Baylis Flillman,360 Mukaiyama Aldol reactions,36 363 reductions of ketones to alcohols 364 and stereoselective nucleophilic additions to aldehydes.365... 

The Sakurai allylation works with a variety of Lewis acid catalysts such as TiCU, AICI3, SnCl4, LtAICL, in addition to BF3 OEt. Reviews (a) Denmark, S. E. Almstead, N. G. In Modem Carbonyl Chemistry Otera, J., Ed. Wiley-VCH Weinheim, 2000 Chapter 10 Allylation of Carbonyls Methodology and Stereochemistry, pp. 299-402. (b) Chemler, S. R. Roush, W. R. In Modern Carbonyl Chemistry, Otera, J., Ed. Wiley-VCH Weinheim, 2000 Chapter 11 Recent Applications of the Allylation Reaction to the Synthesis of Natural Products, pp. 403-490. (c) Demnark, S. E. Fu, J. Chem. Rev. 2003,103, 2763-2793. 

A remote steric effect in the Sakurai-Hosomi addition to unsaturated esters (156) (Scheme 23 Table 4), containing smaU to large alkyl groups, has been detected, which leads to either cyclobutane (157) (—78°C) or allyl adducts (158) (> —50°C). By contrast, the j8-dicarbonyl derivative (159) affords only the normal addition product (160) even at -98 °C. ... 

If one compares the reactions of allyl/crotylboronates and Sakurai-Hosomi addition of allyl/crotylsilanes bearing chiral auxiliaries with one-point attachment (225, 226 Figure 10.9), the enantiomeric excesses of homoallylic products so-formed are much higher in the former than for the products in the latter reactions. ... 

In the presence of In powder 2-cycIohexen-l-one is converted by allyl iodide and Me3SiCI 14, in 63% yield, into the 1,4-addition product 2179 [84], which is also obtained in 73% yield by Sakurai 1,4-addition ofallyltrimethylsilane 82 to 2-cyclohexene-l-one in the presence of excess Me3SiCl 14 and catalytic amounts of InCl3 [85] (Scheme 13.25). Ytterbium] 111) triflate-catalyzed imino-ene reactions of N-tosylaldimines with a-methylstyrene are dramatically accelerated on addition of Me3SiCl 14 [85 a]. 

A variety of electrophilic catalysts promote the addition of allylic silanes to carbonyl compounds.86 The original catalysts included typical Lewis acids such as TiCl4 or BFj.87 This reaction is often referred to as the Sakurai reaction. 

Allylation of aldehydes or ketones using allylsilanes, known as the Hosomi-Sakurai reaction, is a useful method for obtaining homoallylic alcohols. TiIV compounds have been successfully applied to this reaction (Scheme 21) 80 Besides aldehydes and ketones, acylsilanes, 0,0-acetals, and A-,(7-acetals can be employed.81-83 1,4-Addition of an allyl group to an a,/ -unsaturated ketone has been also reported.84... 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

Scott G. Nelson of the University of Pittsburgh has developed (J. Org. Chem. 2005, 70,4375) a highly diastereocontrolled route to substituted cyclohexanones using the intramolecular Sakurai reaction. The requisite ally silane 12 was prepared by Claisen rearrangement of the allylic alcohol 10, followed by homologation. The Ti enolate from the Sakurai addition was trapped with isobutyraldehyde to give 13. Although 32 diastereomers of 13 are possible, the diastereomer illustrated was the dominant product from the cylization. Note that use of the enantiomerically-pure form of the alcohol 10 would have led to enantiomerically-pure 13. 

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... 

Sakurai et al. as well as Sandhoff et al. used this approach for the synthesis of allyl-C-glycopyranosides 21 from readily accessible peracetylated or perbenzylated glycopyranoses 19 [12, 13]. Addition of allylsilane to oxonium 20 proceeds with an axial/equatorial selectivity that is considerably affected by the polarity of the solvent (Scheme 13.9). 

Another successful method for the highly diastereoselective silicon allylation reaction is the allyltrifluorosilane- cesium fluoride system discovered by Sakurai et al. in 1987s (Scheme 3.2e). After a mixture of aldehyde,the allylic trifluorosi-lane 4, and cesium fluoride in a ratio of 1 2 23 was stirred in THF, the reaction mixture was quenched with a solution of HC1 in MeOH to afford the products desired (5) in excellent yield and exceptionally high diastereoselectivity. In addition, the reaction is highly regioselective in that the carbon-carbon bond formation occurs exclusively at the ycarbon of allylic silanes. 

Most desirable, however, would be chiral catalysts for the addition of the more readily available and less toxic allyl silanes, but so far the efforts towards an enantioselective variant of the Sakurai-Hosomi reaction have been less successful. Some time ago Ketter and Herrmann [3a] obtained 24 % ee for the addition of allyl silane to aldehydes catalyzed by the dichlorotitanate 1. 

Better results (80 % ee) have been reported by Mikami, Nakai and co-workers [3c] for the addition of crotyl silane also catalyzed by complex 1. Yamamoto and co-workers [3b] used chiral acyl-oxy boranes to catalyze the Sakurai-Hosomi-reac-tion. While an excellent 96 % ee was obtained for the addition of 2,3 -disubstituted allyl groups, the conversion with parent allyl silane was low (46 %) and the asymmetric induction mediocre (55 % ee). Gauthier and Carreira [5] then made a big leap forward by using the difluorotita-nium-binaphthol complex 3. The catalyst 3 is prepared in situ via the TiF4-binaphthol adduct 4 and formal HF elimination mediated by allyl silane 5. The addition of 5 to aldehydes 6 ( 7) catalyzed by 10 % of 3 proceeds with 61 - 94 % < e and good yields (69-93 %), the best results being observed for aldehydes with tertiary alkyl residues (Scheme 1). 

Conjugate addition to acyclic Michael acceptors. Sakurai and Hosomi (9, 445-446) reported one example of the fluoride ion-catalyzed reaction of allyltrimethylsilane with an acyclic enone. In that case (reaction with C6H5CH=CHCOCH,). 1.2- and 1,4-adducts are obtained in the ratio 2 1.1,4-Addition is enhanced by use of DMF and HMPT as solvent and by increase in the size of the group adjacent to the carbonyl group. 1,4-Addition is the main or predominant reaction with a,3-unsaturated esters or nitriles. In this case, it is superior to or competitive with allylation with lithium diallylcuprate. Yields in 1,4-additions to a,p-enones can compare favorably with those obtained with reactions catalyzed by TiC. ... 

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-... 

Since the discovery of thermally promoted allylation of aldehydes [9], allylstannanes have been widely used in organic synthesis as stable and stereodefined reagents for C-C bond formation. Although it had been reported that activated aldehydes [10] or allylstannanes with chloride on the tin [11] could be used for allylation, remarkably innovative technology for allylation was advanced by Naruta and by Sakurai and Hosomi [12]. They disclosed that allylation was promoted by addition of a Lewis acid this substantially expanded the versatihty of the aUylstaimane procedure. Because many allylation reactions have already been documented [1], the most recent progress in this field will be described after brief description of fundamental aspects. 

Protic-acid-catalyzed Michael additions (59) are subject to most of the limitations of base-catalyzed Michael additions (regioselectivity and stereoselectivity of enol generation, polyaddition, etc.), and hence, the stereochemistry has been little studied (60). At low temperatures silyl and stannyl enol ethers,+ ketene acetals, and allyl species are unreactive to all but the most reactive activated olefins. However, it was discovered by Mukaiyama and co-workers that enol ethers and ketene acetals react with a,/f-unsaturated carbonyl compounds in the presence of certain Lewis acids (4,61,62). Sakurai, Hosomi, and co-workers found that allylsilanes behave similarly (5,63,64). 

Modified Sakurai reaction.3 The original reaction involved the TiCI4-catalyzed addition of allyllrimclhylsilanc to aldehydes and ketones or the acetals and kctals to form homoallylic alcohols or ethers (7,370-371). Marko et al. have extended this reaction to a synthesis of homoallylic ethers by a Lewis acid catalyzed reaction of allyl-trimcthylsilanc with a carbonyl compound and a trimethylsilyl ether. 

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