Reductions trialkylboranes

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

An indirect method ° of double-bond reduction involves hydrolysis of boranes (prepared by 15-16). Trialkylboranes can be hydrolyzed by refluxing with carboxylic acids,while monoalkylboranes RBH2 can be hydrolyzed with base. ° Triple bonds can be similarly reduced, to cis alkenes. °... 

Another example of great synthetic interest, involves the hydroboration reaction of alkenes [62], In general, the addition of borane to alkenes proceeds stepwise, the final product being the trialkylborane. However, hindered alkenes react slowly, especially when the dialkylborane precipitates from the medium. It was found that trialkyl bor-anes could be obtained rapidly under sonication, even with highly hindered substrates (Eq. 3.5). Applications of this useful modification were published, among which were the reduction-hydroxylation of vinyl groups by 9-BBN [63,64]. 

Similar reductions are achieved by trialkylboranes [S26]. These reactions, although different in nature from the reductions by hydrides and complex hydrides, were amongst the first applications of boranes and alanes for the reduction of organic compounds. 

When the reaction between a trialkylborane and carbon monoxide (8-24) is carried out in the presence of a reducing agent such as lithium borohydride or potassium triisopropoxy-borohydride, the reduction agent intercepts the intermediate 73, so that only one boron-to-carbon migration takes place, and the product is hydrolyzed to a primary alcohol or oxidized to an aldehyde.333 This procedure wastes two of the three R groups, but this problem can be avoided by the use of B-alkyl-9-BBN derivatives (p. 785). Since only the 9-alkyl group... 

Figure 3.27 shows reaction equations and the energy relationships of the hydroboration of enantiomerically pure a-pinene with 9-BBN. The reagent approaches only the side of the C=C double bond that lies opposite the isopropylidene bridge. The addition is thus completely diastereoselective. Moreover, the trialkylborane obtained is a pure enantiomer, since the starting material is a pure enantiomer. It is used as Alpine-Borane for the enantioselec-tive reduction of carbonyl compounds (Section 10.4). 

In 2005, Wood and co-workers reported a conceptionally new version of the Barton-McCombie reaction by using water as hydrogen-atom source for the reduction of free radicals in the presence of trialkylboranes (Scheme 35) [85]. 

Scheme 37 Rate constant of the reduction of secondary radicals by trialkylborane coordinated water...

The Overall process of reduction of an alkene to an alkane, or of reduction of an alkyne to either an al-kene or an alkane, via hydroboration requires that the intermediate organoborane be protonolyzed (Section 3.10.1.1). However, simple trialkylboranes are remarkably resistant to hydrolysis. For example, trimethylborane gives only 69% of hydroxydimethylborane after 7 h at 180 °C with 1 equiv. of water. Similar resistance is shown to alcohols, phenols and amines, and even mineral acids do not completely protonolyze trialkylboranes with any ease. Thus, aqueous or anhydrous hydrogen bromide removes only one alkyl group from tributylborane after reflux for 1 h. ... 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

Trialkylboranes are also effective chelation agents in stereoselective NaBH4 reductions of P-hydroxy ketones to 1,3-syn diols. ... 

Reduction using boranes. A practical modification of the oxazaborolidine-catalyzed reduction of ketones with borane is to replace the trialkylborane component with trimethyl borate. For the reduction of (3-silyl and ( -stannyl enones the use of 80 is advocated. ... 

A general synthesis of mixed trialkylboranes and alkylalkenylalkynyl-boranes is based on a hydroboration-reduction sequence starting with dihalo-genoborane ... 

Two equivalents 1-alkyne with thexylborane produces the thexyldialkenylboranes . Thexylalkylalkenylboranes can be obtained either by sequential hydroboration of an alkene-alkyne pair with thexylborane [Eq. (ct)] or via hydroboration of an alkene with thexylchloroborane, followed by reduction and hydroboration of an alkyne [Eq. (cw)]. Cyclic trialkylboranes are synthesized via hydroboration. Thus, HjB-THF reacts 2 3 with simple acyclic dienes to give predominantly the dumbbell-shaped organoboranes. When heated, they undergo isomerization to the more thermodynamically stable isomers. These empirical rules predict their thermal behavior (a) the thermal... 

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