Boronic esters asymmetric synthesis

Cyclic esters of a-halo boronic acids in asymmetric synthesis 98T10555. 

ANTI-SELECTIVE BORON-MEDIATED ASYMMETRIC ALDOL REACTION OF CARBOXYLIC ESTERS SYNTHESIS OF (2S, 3R)-2,4-DIMETHYL-1,3-PENTANEDIOL... 

The use of a-halo(alkyl) boronic esters in asymmetric synthesis provides state of the art stereoselection1-3. The diastereomeric ratio of the a-halo boronic esters synthesized as intermediates is routinely in the 100 1 range. However, with the proper choice of chiral director, displacement of the oc-halogen provides a second stcrcodifferentiation step, after which diastereomeric ratios may exceed 1000 1 4. 

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. 

In the initial discovery of the asymmetric synthesis of a-chloro boronic esters 3, the diastereomeric ratios of 3 were estimated by reaction with Grignard reagents to form secondary alkyl boronic esters 5 and deboronation with hydrogen peroxide to secondary alcohols of known absolute configuration and rotation40. 

These difficulties of asymmetric synthesis of a-alkoxy boronic eslers are disappointing inasmuch as these esters are particularly useful in the chirality transfer reaction with aldehydes, reviewed in Section D.1.3.3.3.3. 

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... 

Cyclic boronic esters in asymmetric synthesis 88ACR294 89T1859. Cyclic a-halo boronic esters in asymmetric synthesis 89CRV1535. B-Heterocycles as structure fragments of polymers 88UK1529. B,N-Heterocycles in the synthesis of boron nitride 90CRV73. B,P-Heterocycles 90AG(E)449. 

This iterative procedure has been utilized with great effect in asymmetric synthesis via chiral boronic esters derived from chiral alcohols. ... 

Oppolzer has developed a method of asymmetric synthesis based on the use of the chiral auxiliaries 39A and 39B derived respectively from (+ )-camphor [(+ )-40] and (- )-camphor [(- )-40]. Crotonylation of 39A gave the ester that was attacked by 4-methyl-3-pentenyllithium in the presence of copper iodide tributylphosphine and boron trifluoride from only one side of the molecule, the product 41 having the (S)-configuration (enantioselectivity 98.5%). The ester 42—similarly obtainable from 39B—was methylated under similar conditions, also yielding 41 with 92% enantioselectivity. (S)-Citronellic acid [(S)-36] or (S)-citronellol [(S)-33] were then obtained from 41 by the action of sodium hydroxide or lithium aluminum hydride (Scheme 6). Reduction of potassium... 

Asymmetric synthesis by means of a-halo boronic esters intermediates leading to drial aldehydes. 

A general synthesis of a-chiral ketones with essentially 100% ee is based on the utilization of boronic esters. These esters can be prepared by asymmetric hydroboration of prostereogenic olefins and subsequent removal of the chiral auxiliary. Two approaches to a-chiral ketone formation are known ... 

Recent Progress in Asymmetric Synthesis with Boronic Esters... 

In earlier work, we had shown that a-azido boronic esters are surprisingly stable and will undergo the reaction with (dichloromethyl)lithium, albeit with some complications caused by azide reactivity (1). We have also used azido boronic esters as intermediates in an asymmetric amino acid synthesis (21). It now appears that azido boronic esters may be the best general protected amine functionality for synthetic purposes, and we will report new flndings in this area shortly (22). Older findings with azido boronic esters as well as the compatibility or incompatibility of other polar functionality with boronic ester chemistry have been reviewed elsewhere recently in considerable detail (23). 

The utility of (a-haloalkyl)boronic esters in asymmetric synthesis results from a unique combination of several features of their chemistry. A wide variety of products can be obtained in very high stereopurity, and the reactions are compatible with a considerable variety of functional substituents, provided that OH and NH groups are masked. Stereospecific displacement of halide from an (a-haloalkyl)boronic ester with a nucleophile yields an asymmetric boronic ester, which can either be converted stereospecifically into another product such as an alcohol or put into another cycle of reaction with (dihalomethyl)lithium to install additional stereocenters. The general synthetic utility of these boronic esters can best be understood from a detailed outline of the general processes involved. 

The first synthesis of an (a-haloalkyl)boronic ester [8], a free radical addition of a tetrahalomethane, was followed by mechanistic studies that indicated the potential for stereospecific alkylation with Grignard reagents via borate intermediates [9], if only there had been a way to obtain asymmetric examples. The discovery of the efficient reaction of (dichloromethyl)lithium with boronic esters to form (a-chloroalkyl)boron-ic esters by insertion of a CHCl group into the B-C bond opened a new opportunity [10]. Boronic esters of pinanediol, prepared from (+)-a-pinene by osmium tetroxide catalyzed oxidation, were soon found to undergo the insertion reaction with a strong asymmetric bias, with diastereomeric selectivities frequently in the 90-95% range [llj. It was subsequently found that anhydrous zinc chloride promotes the reaction and increases diastereoselectivity to as high as 99.5% in some cases [12]. 

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