Nucleophiles homochiral, reaction with

The first issue confronted by Myers was preparation of homochiral epoxide 7, the key intermediate needed for his intended nucleophilic addition reaction to enone 6. Its synthesis began with the addition of lithium trimethylsilylacetylide to (R)-glyceraldehyde acetonide (Scheme 8.6).8 This afforded a mixture of propargylic alcohols that underwent oxidation to alkynone 10 with pyridinium dichromate (PDC). A Wittig reaction next ensued to complete installation of the enediyne unit within 11. A 3 1 level of selectivity was observed in favour of the desired olefin isomer. After selective desilylation of the more labile trimethylsilyl group from the product mixture, deacetalation with IN HC1 in tetrahydrofuran (THF) enabled both alkene components to be separated, and compound 12 isolated pure. 

The activation of nitrones using (la) enables their reactions with carbon nucleophiles such as silyl enolates, allylsilanes, and allylstannanes [143]. Lombardo and Trombini successfully utilized the (la)-catalyzed reaction of homochiral nitrone (90) with 2-trimethylsiloxyfuran for an efficient asymmetric synthesis of a protected 1,2,7,8-indolizidinetetrol, whose deprotected form is attractive as a glycosidase inhibitor [144] (Scheme 9.59). They have recently found that an allylzinc reagent smoothly adds to nitrones in the presence of (la) [145]. 

In view of the successful preparation of so many homochiral sulfoxides via the reaction of nucleophilic species with sulfinate ester 19, it appears likely that the reaction is capable of extension to provide still more examples of potentially useful sulfoxides. 

Scheme 3-56 shows an example of the generation of chiral amines via nucleophilic attack onto an imine substrate in the presence of an external homochiral auxiliary. Moderate ee can be obtained from 161-induced reactions, and moderate to high ee can be expected from 162-induced reactions. For instance, when 161 (R1 = Et, R2 = t-Bu) is involved in the reaction, nucleophilic attack of RLi (R = Me, -Bu. and vinyl) on imine 163 gives product 164 with 81-92%... 

The dilithio derivative of 1,4-bisphenylsufonylbutane 61 was formed prior to the introduction of homochiral acylsilane 56 into the reaction mixture. The nucleophilic carbonyl addition/Brook rearrangement/elimination sequence delivered bis (fi)-vinyl silyl ether 64 in high yield and with very high selectivity through the putative intermediates 62 and 63. This short and effective synthesis of 55, this time made as the major isomer, was then completed as described above for 54. 

The direction of addition (syn or anti) with amine nucleophiles has been tested and fonnd to be dependent on the reaction conditions. The sitnation is clearest with the homochiral cyclohexane derivative (Scheme 15). In this example, a simple Pd catalyst gives a mixture of isomers owing to competitive syn and anti addition, while the polymer-supported catalyst produces only the (usual) anti addition. ... 

Disubstituted phenols such as 350 undergo PhI(OAc)2-mediated oxidation in the presence of MeOH as a nucleophile resulting in the formation of two possible cyclohexa-dienones (351 and 352) (Scheme 73). The initially formed intermediate 353 is converted to the cyclohexadienones by two plausible routes. In route A, heterolytic dissociation generates a solvated phenoxonium ion 354, which further reacts with MeOH to afford 351 and/or 352. In route B, both 351 and 352 are produced by direct attack of MeOH on the intermediate (353). In the latter case, the reaction will be strongly influenced by steric factors and a homochiral environment using chiral solvents and chiral oxidants to induce some asymmetric induction, particularly in the formation of 352. 

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