Chiral epoxides via borane reduction of 2-haloketones catalyzed by spiroborate ester: application to the synthesis of optically pure 1,2-hydroxy ethers and 1,2-azido alcohols.

An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.

Chiral spiroaminoborate ester as a highly enantioselective and efficient catalyst for the borane reduction of furyl, thiophene, chroman and thiochroman containing ketones.

Prochiral heteroaryl ketones containing furan, thiophene, chroman and thiochroman moieties were successfully reduced in the presence of 1 - 10 mol % of spiroaminoborate ester 1 with different borane sources to afford non-racemic alcohols in up to 99% ee. In addition, modest enantioselectivity, around 80% ee, was achieved in the reduction of linear α,β-unsaturated heteroaryl ketones.

Spiroborate ester-mediated asymmetric synthesis of beta-hydroxy ethers and its conversion to highly enantiopure beta-amino ethers.

Borane-mediated reduction of aryl and alkyl ketones with alpha-aryl- and alpha-pyridyloxy groups affords beta-hydroxy ethers in high enantiomeric purity (up to 99% ee) and in good yield, using as catalyst 10 mol % of spiroborate ester 1 derived from (S)-diphenylprolinol. Representative beta-hydroxy ethers are successfully converted to beta-amino ethers, with minor epimerization, by phthalimide substitution under Mitsunobu's conditions followed by hydrazinolysis to obtain primary amino ethers or by imide reduction with borane to afford beta-2,3-dihydro-1H-isoindol ethers. Nonracemic Mexiletine and nAChR analogues with potential biological activity are also synthesized in excellent yield by mesylation of key beta-hydroxy pyridylethers and substitution with five-, six-, and seven-membered ring heterocyclic amines.

A practical and efficient route for the highly enantioselective synthesis of mexiletine analogues and novel beta-thiophenoxy and pyridyl ethers.

A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel beta-amino ethers containing thiophenyl and pyridyl fragments.

Highly enantioselective borane reduction of heteroaryl and heterocyclic ketoxime ethers catalyzed by novel spiroborate ester derived from diphenylvalinol: application to the synthesis of nicotine analogues.

An asymmetric synthesis for the preparation of nonracemic amines bearing heterocyclic and heteroaromatic rings is described. A variety of important enantiopure thionyl and arylalkyl primary amines were afforded by the borane-mediated enantioselective reduction of O-benzyl ketoximes using 10% of catalyst 10 derived from ( S)-diphenylvalinol and ethylene glycol with excellent enantioselectivity, in up to 99% ee. The optimal condition for the first asymmetric reduction of 3- and 4-pyridyl-derived O-benzyl ketoxime ethers was achieved using 30% of catalytic loading in dioxane at 10 degrees C.

Spiroborate esters in the borane-mediated asymmetric synthesis of pyridyl and related heterocyclic alcohols.

The effectiveness of several spiroborate ester catalysts was investigated in the asymmetric borane reduction of 2-, 3-, 4-acetylpyridines under different reaction conditions. Highly enantiomerically enriched 1-(2-, 3- and 4-pyridyl)ethanols and 1-(heterocyclic)ethanols were obtained using 1 to 10% catalytic loads of the spiroborate 5 derived from diphenylprolinol and ethylene glycol.

Enantioselective Reduction of Prochiral Ketones using Spiroborate Esters as Catalysts.

Novel spiroborate esters derived nonracemic 1,2-aminoalcohols and ethylene glycol are reported as highly effective catalysts for the asymmetric borane reduction of a variety of prochiral ketones with borane-dimethyl sulfide complex at room temperature. Optically active alcohols were obtained in excellent chemical yields using 0.1 to 10 mol % of catalysts with up to 99% ee.

Asymmetric synthesis of primary amines via the spiroborate-catalyzed borane reduction of oxime ethers.

[reaction: see text] The enantioselective borane reduction of O-benzyloxime ethers to primary amines was studied under catalytic conditions using the spiroborate esters 5-10 derived from nonracemic 1,2-amino alcohols and ethylene glycol. Effective catalytic conditions were achieved using only 10% of catalyst 5 derived from diphenylvalinol in dioxane at 0 degrees C resulting in complete conversion to the corresponding primary amine in up to 99% ee.

Efficient synthesis of B-alkylated oxazaborolidines derived from ephedrine and norephedrine.

[reaction: see text] Representative B-butyl- and B-methyl-1,3,2-oxazaborolidines derived from ephedrine and norephedrine were prepared in good yield and excellent purity by one-pot treatment of B-H oxazaborolidines with the corresponding organolithium reagent and subsequent hydrolysis of the cyclic borohydride intermediate with anhydrous ammonium chloride.