Homochiral nucleophiles oxide

Homochiral nucleophiles such as (15) give a pure stereoisomer in high yield when reacted with ethylene oxide in the presence of BF3.Et20.35... 

The RLi homochiral ligand complexes are seldom used for the base-promoted isomerization of oxiranes into allylic alcohols because their poor chemoselectivity lead to complex mixtures of products. As examples, the treatment of cyclohexene oxide by a 1 1 i-BuLi/(—)-sparteine mixture in ether at low temperature provides a mixture of three different products arising respectively from -deprotonation (75), a-deprotonation (76) and nucleophilic addition (77) (Scheme 32) . When exposed to similar conditions, the disubstituted cyclooctene oxide 78 affords a nearly 1 1 mixture of a- and -deprotonation products (79 and 80) with moderate ee (Scheme 32, entry 1). Further studies have demonstrated that the a//3 ratio depends strongly on the type of ligand used (Scheme 32, entry 1 vs. entry 2) . ... 

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. 

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. 

There are several efficient methods available for the synthesis of homochiral sulfoxides [3], such as asymmetric oxidation, optical resolution (chemical or bio-catalytic) and nucleophilic substitution on chiral sulfinates (the Andersen synthesis). The asymmetric oxidation process, in particular, has received much attention recently. The first practical example of asymmetric oxidation based on a modified Sharpless epoxidation reagent was first reported by Kagan [4] and Modena [5] independently. With further improvement on the oxidant and the chiral ligand, chiral sulfoxides of >95% ee can be routinely prepared by these asymmetric oxidation methods. Nonetheless, of these methods, the Andersen synthesis [6] is still one of the most widely used and reliable synthetic route to homochiral sulfoxides. Clean inversion takes place at the stereogenic sulfur center of the sulfinate in the Andersen synthesis. Therefore, the key advantage of the Andersen approach is that the absolute configuration of the resulting sulfoxide is well defined provided the absolute stereochemistry of the sulfinate is known. 

Having now reduced the challenging architecture of the CP-molecules to structure 17, the benefit of previously symmetrizing the C-14 center should finally be clear as it opened several avenues to create this new subtarget using simple materials. For example, the addition of a vinyl nucleophile such as 18 to aldehyde 19, followed by an oxidation step to complete the requisite o,p-un-saturated system, could constitute one approach to deliver this key Diels—Alder precursor (17). Had the C-14 carbon in 17 still been homochiral, such facility would not exist since its specific positioning makes an efficient asymmetric synthetic route, or the identification of a suitable starting material that could be elaborated to such an adduct, quite difficult to envision. 

With a little more sophisticated system employing benzoyl fluoride and a homochiral base, the enatioselective, nucleophilic ring opening of cyclohexene oxide was achieved in moderate to good yields (see 648) [251]. 

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