Chiral deriv reagents, selection

Further optimization of this reaction was carried out with TFE as an achiral adduct, since reaction with TFE is much faster than that with neopentyl alcohol. We found that dimethyl- and diethylzinc were equally effective, and the chiral zinc reagent could be prepared by mixing the chiral modifier, the achiral alcohol and dialkylzinc reagent in any order without affecting the conversion and selectivity of the reaction. However, the ratio of chiral to achiral modifier does affect the efficiency of the reaction. Less than 1 equiv of the chiral modifier lowered the ee %. For example with 0.8 equiv of 46 the enantiomeric excess of 53 was only 58.8% but with 1 equiv of 46 it was increased to 95.6%. Reaction temperature has a little effect on the enantiomeric excess. Reactions with zinc alkoxide derived for 46 and TFE gave 53 with 99.2% ee at 0°C and 94.0% ee at 40°C. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

In some cases (3), the addition of a chiral shift reagent (Eu(hfc)3) is necessary to obtain baseline separation of the signals corresponding to the p-proton of both diastereomers by H NMR. Diastereomeric mixtures derived from secondary alcohols have also been analyzed by HPLC. The resolution of a secondary alcohol (4) could be achieved by a selective crystallization of one of the two diastereomeric camphorsulfonate esters. ... 

Application of the external chiral boron reagent (90) in the totd synthesis of bryostatin, a natural product, is shown in Scheme 45. The convergent approach adopted involves coupling of the boron enolate derived from (111) with aldehyde (112). The reaction mediated by an achiral boron reagent (Et2BOTf) provides only a 2 1 preference for the formation of the desired isomer (115) in adduct (113). The use of chiral (2/ ,5 )-dimethylborolanyl triflate in this reaction increases the selectivity to a 6 1 preference as... 

When the boron ligands and the aldehyde are both chiral, the inherent stereoselectivities of each partner may be either matched or mismatched (Chapter 1). In principle, a chiral aldehyde could derive facial selectivity from either the Felkin-Anh-Heathcock model (Figures 4.8 and 4.10) or the Cram-chelate model (Figure 4.11). However, because the boron of these reagents can accept only one additional ligand, chelation is not possible. Therefore only the Felkin-Anh-Heathcock effects... 

Asymmetric allylation and crotylation, synthetically equivalent to the aldol reaction, have been extensively studied and have become a very useful procedure for preparation of propionate units. Among various chiral ligands on boron-developed, isopinocampheyl- and tartrate-derived reagents, 51 and 52, which were developed by Brown et al. [18] and Roush et al. [19], respectively, are the most commonly used (Scheme 7). Reaction of aldehyde with (Sl-Sla or 52a gave anu -adduct 54, while that using (Z)-51b or 52b afforded syn-adduct 53 with high asymmetric selectivity. 

Utilizing the menthol-derived chiral tin reagents 77-80 in conjunction with bulky Lewis acids such as zirconocene dichloride or a manganese-salen complex, selective reductions of esters (81a-d) offered excellent levels of selectivity up to 96% ee in a 75% yield (for reduction of 81c) [36], Chiral stannane 80 offered the most consistent high levels of enantioselectivity for reduction of all substrates, ranging from 62% ee to above 90% ee in many cases with a bulky Lewis acid additive. 

Some organotin ethers of carbohydrate derivatives have been synthesised as potential pestiddes and the selected acylation of some cyclic dibutylstannylene compounds is discussed in Chapter 7. Treatment of cyclopentadienyltitanium trichloride with l,2 5,6-di-0-isopropylidene-a-D-glucofuranose affords adduct (26) which may be transformed into the chiral organometallic reagents (27)-(29). These react with aldehydes (RCHO) to give products (30)-(32), respectively, with high stereoselectivity. ... 

A few examples showcasing double stereodifferentiation phenomena are outlined below. In the case of crotylation of a-alkoxy-substituted aldehyde 72, Roush observed a reversal of facial selectivity with either enantiomer of the chiral ( )-crotylboronate reagent 29 (Scheme 5.13) [48]. Similarly, Brown found that the pinene-derived crotyl boranes 76 and 77 provide access to all four stereotriads 78-81 with impressive stereoselectivity with use of either the ( )- or the (Z)-crotyl reagent (Scheme 5.14) [77]. 

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