Enantiomeric purity chiral diols

An extremely attractive feature of the route outlined at the beginning of this section for the transformation of boronates 3 or 4 to a-substituted allylboron compounds 5 is that reagents with very high enantiomeric purity (> 90% ee) may be prepared when precursors such as 3 and 4, and therefore also ate complex 1, contain a suitable diol chiral auxiliary17. The following syntheses of (S)-68, lib9, and 1310 illustrate this feature. 

This material, which is contaminated with the chiral ligand, is sufficiently pure to b e used in the next step. A small portion of the cmde diol (479 mg) was purified by column chromatography (SiOj, 30 x 160 mm, 4/1 hexane/ ethyl acetate) to yield a white solid (430 mg, 90%). The enantiomeric purity of the cmde product was determined to be 99.4% ee... 

Olefins of the /ranr-disubstituted type have given diols with excellent enantiomeric purities when dihydroxylated with the (DHQD)2-PHAL/(DHQ-PHAL pair of chiral ligands with osmium tetroxide (see Table 6D.3 [16,26,29,31,35,40,41,46-48]). All the entries but one in Column 9 for diols obtained with these ligands exceed 90% ee (or 90% de). From other entries in Table 6D.3, particularly those of Column 3 for earlier stoichiometric ADs with the DHQD-CLB ligand, good enantioselectivities are anticipated for the dihydroxylation of most trans-disubstituted olefins when the PHAL ligands are used. 

Included in this class of olefins is ( )-stilbene (entry 20), which throughout studies of AD has usually been the olefin dihydroxylated with the highest degree of enantioselectivity. Availability of (R,R) or (.5,5)-1,2-diphenyl-1,2-ethanediol (also referred to as stilbenediol or dihydrobenzoin) with high enantiomeric purities has led to reports of a number of applications, including incorporation into chiral dioxaphospholanes [50], chiral boronates [51], chiral ketene acetals [52], chiral crown ethers [53], and conversion into 1,2-diphenylethane-1,2-diamines [54]. Dihydroxylation of the substituted rran.r-stilbene 46 with Os04/NMO and DHQD-CLB gives the i ,/ -diol 47 with 82% ee in 88% yield [55]. 

A listing of trisubstituted olefins that have been subjected to catalytic AD is given in Table 6D.5 [29,31,40]. Only three compounds of this type have been dihydroxylated by using the newer, more efficient chiral ligands, and all three are converted to diols with high enantiomeric purities under these conditions. 

Diols of different structures such as the meso-diol 76 (Fig. 41), the C2-symmetric diol rac-79 (Fig. 42), the diol rac-82 in which the primary hydroxy group is protected (Fig. 43) and the unprotected diol rac-84 with a primary and secondary hydroxy group (Fig. 44) were used as substrates in the lipase-catalyzed transesterification using vinyl acetate as acyl donor in organic solvents with the aim to prepare chiral buildings blocks of high enantiomeric purity.86... 

Stereochemical information on the mode of cyclodehydration of unsymmetrical diols to cyclic ethers could obviously have important consequences regarding useful, preparative routes to chiral cyclic ethers of high enantiomeric purity. For example, dioxyphos-phorane promoted cyclodehydration of a chiral diol can, in principle, give the enantiomeric ethers by either of two stereochemi-cally distinct routes. Separate stepwise decomposition of oxy-phosphonium betaines, A and B, although proceeded by a number of equilibria could ultimately afford a nonracemic mixture of cyclic ethers. 

Sharpless epoxidation of symmetrical diols can be expected, on purely mathematical grounds, to produce diepoxide products whose enantiomeric purities are dramatically increased over those obtained for formation of a single epoxide56. Hoyle56 recently exploited the double Sharpless epoxidation of a symmetrical diol 12 to produce epoxides 13, 14 and 15 that were required for subsequent conversion to chiral 2,5-linked bistetrahydrofurans. Although the diastereomeric ratios and enantiomeric purities could not be determined, it was possible to calculate that if the enantiofacial selectivity was 19 1 (90% ee) for a single epoxidation, the ratios of isomers would be 361 38 1 for 13/14/15. Thus, in this double enantioselective epoxidation the diastereomeric excess of the chiral diepoxide (13, 15) is expected to be 99.45%. 

Yet another demonstration of the versatility of epoxybutene comes from the asymmetric center, which has been converted into a number of four-carbon chiral synthons, such as 3-butene-1,2-diol and various derivatives, in >99% enantiomeric purity (20,21). 

Miscellaneous.- A simple method to resolve racemic l,l -binaphthalene-2,2 -diol involves reaction with menthyl phosphorodichloridite (139) and separation of the diastereomeric phosphites by crystallisation from ether. The new cyclic chlorodiaminophosphine (140), prepared in and two new cyclic triaminophosphines (141) have been used to determine the enantiomeric purity of chiral alcohols, thiols, and amines by means of Ip n.m.r. New optically pure phosphites used for Rh catalysed asymmetric hydroformylation reactions are (142), two diastereomers of (143), and (144) the diphosphinite (145) was similarly employed. Some new cyclic aminophosphines (146) were prepared for use as ligands in asymmetric Pd catalysed allylic substitution reactions. 

Several boron-containing species have been used as chiral NMR derivatizing agents for the analysis of primary amines or diols. " Most noteworthy among these is 2-for-mylphenylboronic acid 61, which is commercially available. Reaction of 61 with an amine and diol forms a borate-imine as shown in Scheme 50.1. The reaction can be run using an enantiomerically pure amine such as PEA to determine the enantiomeric purity of the diol, or using an enantiomerically pure diol such as BINOL to determine the enantiomeric purity of the amine.The system has been used to determine the enantiomeric purity of amines with remote chiral centers such as l-amino-4-5 ec-butylbenzene and the methyl ester of 2-methyl-5-aminopentanoic acid. 

Kelly AM, Perez-Fuertes T, Fossey JS, Yeste SL, Bull SD, James TD. Simple procedure for NMR analysis of the enantiomeric purity of chiral diols. Nat. Protoc. 2008 3 215-219. 

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

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