Boronate asymmetric diol synthesis

The synthesis of the polyol glycoside subunit 7 commences with an asymmetric aldol condensation between the boron enolate derived from imide 21 and a-(benzyloxy)acetaldehyde (24) to give syn adduct 39 in 87 % yield and in greater than 99 % diastereomeric purity (see Scheme 8a). Treatment of the Weinreb amide,20 derived in one step through transamination of 39, with 2-lithiopropene furnishes enone 23 in an overall yield of 92 %. To accomplish the formation of the syn 1,3-diol, enone 23 is reduced in a chemo- and... 

The first useful asymmetric synthesis with a-halo boronic esters utilized (S)-pinanediol [1S-(la,2/1.3//,5a)]-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol as the chiral director39,40. This diol is easily prepared from ( + )-a-pinene by a catalytic hydroxylation with osmium tetroxide, and its enantiomer (i )-pinanediol is available from (-)-(a)-pinene41,42. Pinanediol esters remain useful in view of their excellent stability as well as the ease of preparation of the diol. and their stereoselectivity is very high even though it is no longer the state of the art. 

The quinoline portion of the target alkaloids was prepared by condensing p-anisidine 9 with ethyl propiolate, followed by bromination. Coupling of 10 with the boronic ester 8 proceeded to give 11, the intermediate for the synthesis of both 1 and 2. Selective direct epoxidation of 11 using the usual reagents failed, but Sharpless asymmetric dihydroxylation was successful, providing the diol in > 96 4... 

In the total synthesis of (+)-trienomycins A and F, Smith et al. used an Evans aldol reaction technology to construct a 1,3-diol functional group8 (Scheme 2.1i). Asymmetric aldol reaction of the boron enolate of 14 with methacrolein afforded exclusively the desired xyn-diastereomer (17) in high yield. Silylation, hydrolysis using the lithium hydroperoxide protocol, preparation of Weinreb amide mediated by carbonyldiimidazole (CDI), and DIBAL-H reduction cleanly gave the aldehyde 18. Allylboration via the Brown protocol9 (see Chapter 3) then yielded a 12.5 1 mixture of diastereomers, which was purified to provide the alcohol desired (19) in 88% yield. Desilylation and acetonide formation furnished the diene 20, which contained a C9-C14 subunit of the TBS ether of (+)-trienomycinol. 

Use of the immobilized iridium double-bond isomerizing catalyst (70) developed for the carpanone synthesis again worked well to convert commercially available 73 to the conjugated product (74). This was then methylated in the presence of PS-BEMP (7), a reaction that proceeds in almost quantitative yield. Next, an asymmetric dihydroxylation was performed according to methods developed by Sharpless. However, instead of using a conventional workup procedure for the vicinal diol (75), a new catch-and-release protocol was developed. This made use of the immobilized boronic acid (76) to trap the chiral diol... 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

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