Silicon Allylation Reaction

Silane Ketone0 syn/antib Yield, % (6) Silane Ketone0 syntantib Yield, % (7) 

In an effort to explain the high levels of diastereoselectivity observed in the crotylation reactions, Sakurai et al. performed a computational study on the 

Although (3-hydroxy ketones are inert toward allyltrifluorosilanes under the reaction conditions mentioned above,10 (3-hydroxy aldehydes do react with allylic 

In 1992, Tietze et al. discovered an elegant method for the direct and simple preparation of homoallylic ethers with excellent de values ( 99%) using the 

The incorporation of silicon into a strained ring provides another avenue for allowing allylsilane reagents to participate in six-membered transition states. Although allyldimethylphenylsilane did not add to benzaldehyde even after heat- 

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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. 

Houk et al. performed a theoretical study on the asymmetric silicon allylation reaction to rationalize the high levels of enantioselectivity realized with... 

Although the allylation reaction is formally analogous to the addition of allylic boranes to carbonyl derivatives, it does not normally occur through a cyclic TS. This is because, in contrast to the boranes, the silicon in allylic silanes has little Lewis acid character and does not coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic TS. The -stereoisomer of 2-butenyl(trimethyl)silane gives nearly exclusively the product in... 

If the latter reaction proceeds through a closed transition state (e.g., 5 in Scheme 7.2), good diastereocontrol can be expected in the case of trans- and cis-CrotylSiCl3 (2b/2c) [14, 15]. Here, the anh-diastereoisomer 3b should be obtained from trans-crotyl derivative 2b, whereas the syn-isomer 3c should result from the reaction of the cis-isomer 2c (Scheme 7.2). Furthermore, this mechanism creates an opportunity for transferring the chiral information if the Lewis base employed is chiral. Provided that the Lewis base dissociates from the silicon in the intermediate 6 at a sufficient rate, it can act as a catalyst (rather than as a stoichiometric reagent). Typical Lewis bases that promote the allylation reaction are the common dipolar aprotic solvents, such as dimethylformamide (DMF) [8,12], dimethyl sulfoxide (DMSO) [8, 9], and hexamethylphosphoramide (HMPA) [9, 16], in addition to other substances that possess a strongly Lewis basic oxygen, such as various formamides [17] (in a solution or on a solid support [7, 8, 18]), urea derivatives [19], and catecholates [10] (and their chiral modifications [5c], [20]). It should be noted that, upon coordination to a Lewis base, the silicon atom becomes more Lewis acidic (vide infra), which facilitates its coordination to the carbonyl in the cyclic transition state 5. 

In the next two sections we examine a number of stereoselective addition reactions of boron and silicon allylic reagents to carbonyl compounds. 

Tietze et al. emphasized the usefulness of chiral trimethylsilyl ethers of readily accessible amino alcohol derivatives in allylation of aldehydes and ketones [43]. As a consequence, careful design of the norpseudoephedrine derivatives and proper choice of silicon Lewis acids have led to the convergent preparation of enantiomerically enriched secondary and tertiary homoallylic alcohols in high yields (Sch. 12) [43a], It should be noted that the configuration of the newly formed stereogenic center of the secondary homoallylic alcohols is the opposite of that in the allylation of ketones [43c], They also described in detail mechanistic studies of the above allylation reaction by use of and NMR. 

The Lewis acidic character of reactive pentacoordinate silicon compounds has been unequivocally confirmed by Corriu, Sakurai and Hosomi [90]. Allylsilicates prepared from allylsilanes and catechol can undergo allylation reaction with aldehydes in the absence of Lewis acid promoter (Sch. 51). 

The most useful of all allyl anion equivalents are the allyl silanes.20 This is because it is easy to make them regioselectively, because they do not undergo allylic rearrangement (silicon does not do a [1,3] shift) and because their reactions with electrophiles are very well controlled addition always occurring at the opposite end to the silicon atom. Symmetrical allyl silanes can be made from allyl-lithiums or Grignards by displacement of chloride from silicon. A useful variant is to mix the halide with a metal, e.g. sodium, and Me3SiCl in the same reaction, rather after the style of the silicon acyloin reaction,21 as in the synthesis of the acetal 80. 

The early phosphoramides 21.9 and 21.10 (Figure 21.1), developed by Denmark, exhibited modest enantioselectivity in the allylation reaction but played an important role in the mechanistic elucidation and development of the second generation of catalysts. Thus, kinetic measurements and the observation of a nonlinear relationship between the enantiopurity of 21.9/21.10 and the product 21.7 indicated that two molecules of the catalyst are coordinated to the silicon centre.However, when the concentration of the catalyst is low, a second mechanism may compete, namely that with only one molecule of the catalyst coordinated, which apparently attenuates the enantioselectivity. As a logical progression from these mechanistic observations, bidentate catalysts, such as 21.12 and 21.13, were designed. The latter exhibited higher enantios-electivities and also was more reactive, so that the loading could be reduced from 10-20 to 5 Excellent diastereoselectivity was... 

Pyridine-type IV-oxides represent another successful class of catalysts for the allylation reaction. They now constitute the most abundant group of nucleophilic activators for silicon reagents. For convenience, the discussion will first focus on catalysts with two or more N-oxide units in the molecule followed by the group of mono-N-oxides. 

Kennedy JWJ, Hall DG (2003) Recent advances in the activation of boron and silicon reagents for stereocontroUed allylation reactions. Angew Chem Int Ed 42 4732-4739... 

There are several excellent methodologies reported in the literature that make use of a variety of aUylating reagents based on boron, silicon, tin, and titanium metals for carbonyl allylation reactions. In the early 1980s, Denmark and Weber developed a classification system for allylation reagents that takes into account their proposed mechanism of addition to the carbonyl moiety (Figure 4). ... 

A further extension of this strategy uses bis-aUyl silicon group as effective substituent for a subsequent intramolecular allylation reaction, providing polyols after oxidative conditions. The transition state that is depicted in Scheme 2.154 rationalizes the facial selectivity observed during the allylation step. 

The effect of the electronic properties of the substituted benzaldehydes (la-c) on the allylation reaction is another interesting issue. While most catalysts shown in Figures 15.1 and 15.2 generally exhibit a rather minor variation in ee (typically with less than 20% difference between the electron-rich and electron-poor aldehydes), METHOX (22) appears to be a particularly tolerant catalyst, exhibiting practically the same enantioselectivity (93-96% ee Table 15.2, entries 1-3) and reaction rate across a range of substrates [28f, 28g]. In contrast, QUINOX (23) stands at the opposite side of the spectrum, showing the most dramatic differences between the electron-rich and electron-poor substrate aldehyde (16-96% ee entries 4-6) [30]. Kinetic and computational studies shed some light on the latter behavior it seems that METHOX prefers an ionic transition state with a pentacoordinate silicon (Scheme 15.4), whereas QUINOX favors the neutral, hexacoordinate species. This hypothesis is, inter alia, supported by the choice of solvents, namely. 

Because the reaction type mentioned above belongs more to the field of Lewis base catalyzed reaction, we will now focus on enantiopure silicon allylation reagents that already incorporate Lewis acidity. The Lewis acidity of tetravalent silicon... 

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

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