Unsaturated ketones with boranes

Reduction of a, -unsaturated ketones to unsaturated hydrocarbon is rather rare, and is almost always accompanied by a shift of the double bond. Such reductions are accomplished in good to high yields by treatment of the p-toluenesulfonylhydrazones of the unsaturated ketones with sodium borohydride [785], borane [786] or catecholborane [559], or by Wolff-Kizhner reduction or its modifications [590]. However, complete reduction to saturated hydrocarbons may also occur during Wolff-Kizhner reduction [597] as well as during Clemmensen reduction [750]. 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

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... 

A modified version of the Brown-Negishi reaction using B-alkylcatechol-boranes was reported (Scheme 32). This novel method is based on a simple one-pot procedure involving the hydroboration of various substituted alkenes with catecholborane, followed by treatment with catalytic amount of oxygen/DMPU/water and a radical trap. Efficient radical additions to a,ft-unsaturated ketones and aldehydes have been reported. Primary alkyl radicals are efficiently generated by this procedure and the reaction has been applied to a 300 mmol scale synthesis of the y-side chain of (-)-perturasinic... 

Ketones containing triple bonds in the a,)3-positions are reduced to the corresponding unsaturated alcohols with sodium cyanoborohydride or tetra-butylammonium cyanoborohydride in 64-89% yields [780]. Thus 4-phenyl-3-butyn-2-one gave 4-phenyl-3-butyn-2-ol [780]. If the same ketone was converted to its p-toluenesulfonylhydrazone and this was reduced with bis benzyloxy)borane, 1-phenyl-1,2-butadiene was obtained in 21% yield [786]. 

Allylic diethylboranes.1 These boranes (2) can be prepared from 1-methyl-cycloalkenes and 2-alkenes by metallation with trimethylsilylmethylpotassium2 followed by reaction with 1. The products react with acetaldehyde to form homoallylic alcohols (3), which can be converted into a,(3- and p,y-unsaturated ketones. 

Hydroboration of the unsaturated ketone was carried out with the very hindered borane 9-BBN and the alkyl borane 268 was coupled with the vinyl bromide 259 without isolation using Pd(0) as catalyst and NaOH to force the transfer of the alkyl group from boron to palladium. The pure trans (E-) coupled product 269 is formed in 85% yield so coupling must be faster than p-elimination in this case. 

Allylic alcohols. The tendency of NaBH4 to effect conjugate reduction of a,/3-unsaturated compounds is greatly reduced by C6F5OH. With borane scavenged by TMEDA or 1-hexene the selectivity is further improved. Only highly reactive ketones and acid chlorides are reduced by this reagent. ... 

Borane, monoalkylboranes and dialkylboranes (such as thexylborane and 9-BBN) were shown to be powerful reducing agents for carbonyl derivatives (sec. 4.6.A). When the B—H unit is removed, as in trialkylboranes, addition to the alkene moiety of a,p-unsaturated ketones or aldehydes occurs. An alkyl group of the borane is transferred to the terminal position of the alkene moiety (1,4-addition) and boron is transferred to the oxygen, giving a boron enolate (sec. 9.4.D). Initial hydroboration of acrolein with tricyclopentylborane gave boron enolate 196.1 0... 

The reduction of the unsaturated ketone succeeds with boranate, or by the Meerwein-Pondorf method. Dehydration with acidic clay catalyst [163], or more conventionally with acids, acidic salts or FeCl3 [165] leads to the product. 

A reaction has been developed for the conversion of a 3-unsaturated ketones into 3-alkyl trans-1,2-diols. Previously it had been shown that addition of MejCuLi to cyclohex-2-enone followed by acid workup gives 3-methyl-cyclohexanone in high yidd. If, after Me2CuLi addition and separation from the black copper-containing precipitate, the reaction mixture is treated with borane, followed by oxidation with alkaline HjOj, a 55% yield of two diols (108) and (109) in a ratio of 87 13 is obtained. Likewise, isophorone (110) was converted into (111) after a two-day hydroboration step in 53% yield. 

The CBS reduction has also proven to be an efficient method for asymmetric reduction of a,ft-unsaturated enones14 and ynones15 (Scheme 4.31). The asymmetric reduction of alkynyl ketones affords propargylic alcohols 30 with high levels of enantioselectivity and in moderate to good yields. Optimized reaction conditions for the reduction are the use of THF at — 30° C, 2 equivalents of chiral oxazaborolidine 28b, and 5 equivalents of borane methyl sulfide complex. 

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