Ketones, reaction with boranes

Oxidation of trialkyl borates and of trialkoxyboroxines. Trialkyl borates, B(0R)3, prepared by reaction of primary and secondary alcohols with borane-dimethyl sulfide, are oxidized by PCC to aldehydes and ketones in good yield. This indirect oxidation of alcohols does not involve formation of water, which could be detrimental in some cases. Of even greater interest, carboxylic acids can be converted into aldehydes by reaction with borane-dimethyl sulfide to form a tri-alkoxyboroxine followed by oxidation with PCC (equation I). 

The reaction is considered to involve formation of the anion of the a-bromo ketone, reaction with the borane. and rearrangement. Use of potassium /-butoxide in /-butanol gave much lower yields. The a-bromo ketones were prepared by the reaction of ketones with cupric bromide in ethyl acetate-chloroform (method of L. C. King and G. K. Ostrum [J. Org., 29,3459(1964)] see 1, 161-162). 

Potassium tert-butoxide Syntheses with boranes a-Alkylation of ketones via a-balogenation and reaction with boranes... 

Trialky I boranes react rapidly with methyl vinyl ketone (and other a,j8-unsaturated ketones) to yield, after hydrolysis, methyl ketones of the indicated structure 4). The reaction with acrolein is analogous to give jS-alkylpropionaldehydes (5). The process is inefficient in that only one of the three alkyl groups of the borane is converted into product, but the rapidity and ease of carrying out the reaction may be adequate... 

Reaction of halo ketones or diazo ketones with boranes 10-112 Carbonylation of alkyl halides... 

Ketones can also be prepared by palladium-catalyzed reactions of boranes or boronic acids with acyl chlorides. Both saturated and aromatic acyl chlorides react with trialkylboranes in the presence of Pd(PPh3)4.233... 

Several alternative procedures have been developed in which other reagents replace carbon monoxide as the migration terminus.11 The most generally applicable of these methods involves the use of cyanide ion and trifluoroacetic anhydride (TFAA). In this reaction the borane initially forms an adduct with cyanide ion. The migration is induced by N-acylation of the cyano group by TFAA. Oxidation and hydrolysis then give a ketone. 

In the late 1960s, methods were developed for the synthesis of alkylated ketones, esters, and amides via the reaction of trialkyl-boranes with a-diazocarbonyl compounds (50,51), halogen-substituted enolates (52), and sulfur ylids (53) (eqs. [33]-[35]). Only one study has addressed the stereochemical aspects of these reactions in detail. Masamune (54) reported that diazoketones 56 (Ri = CH3, CH2Ph, Ph), upon reaction with tributylborane, afford almost exclusively the ( )-enolate, in qualitative agreement with an earlier report by Pasto (55). It was also found that E) - (Z)-enolate isomerization could be accomplished with a catalytic amount of lithium phenoxide (CgHg, 16 hr, 22°C) (54). 

Reaction of halo ketones or diazo ketones with boranes 0-102 Carbonylation of alkyl halides 0-104 Reaction between acyl halides and organometallic compounds 0-105 Reaction between other acid derivatives and organometallic compounds... 

The enantioselective reduction of ketones using oxazaborolidine-borane complexes is a useful synthetic route to chiral alcohols (equation 63). Additives such as simple alcohols have been found to enhance the enantioselectivity of the process, and the reaction has been used in the large-scale synthesis of an important drug with anti arrhythmic properties249. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Selective reduction of ot,a-dihalo ketones." Reduction of a,a-dihalo ketones can he effected without hydrogenolysis of the halo groups with either DIBAH or borane dimethyl sulfide. Reactions with the former reagent are generally faster but work-up can be complicated by gelatinous aluminum salts. In general, the yields are roughly comparable. 

It is more interesting that reduction of complex ketones could be dramatically improved by optimization of the reaction temperature. In the case of the phenoxyphenylvinyl methyl ketone (6), a 5-lipoxygenase inhibitor synthesis intermediate, we were able to improve the enantiomeric excess from the 80-85% range up to 96% by selection of the optimal temperature for the reduction. In this case, the temperature range for an acceptable enantiomeric excess is very narrow. Generally, Me-CBS is the best catalyst with borane complexes as reducing agent. 

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