Dialkylboranes, reduction

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

Primary dialkylboranes react readily with most alkenes at ambient temperatures and dihydroborate terminal acetylenes. However, these unhindered dialkylboranes exist in equiUbtium with mono- and ttialkylboranes and cannot be prepared in a state of high purity by the reaction of two equivalents of an alkene with borane (35—38). Nevertheless, such mixtures can be used for hydroboration if the products are acceptable for further transformations or can be separated (90). When pure primary dialkylboranes are required they are best prepared by the reduction of dialkylhalogenoboranes with metal hydrides (91—93). To avoid redistribution they must be used immediately or be stabilized as amine complexes or converted into dialkylborohydtides. 

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]. 

Other methods are also available for generation of boron enolates. Dialkylboranes react with acyclic enones to give Z-enolates by a 1,4-reduction.19 The preferred Z-stereochemistry is attributed to a cyclic mechanism for hydride transfer ... 

The monoalkylborane, RBH2, and the dialkylborane, R2BH, seldom are isolated because they rapidly add to the alkene. These additions amount to reduction of both carbons of the double bond ... 

Kinetic resolution of vinylic epoxides by the reduction with terpenyl dialkylboranes of high optical purity is a simple and direct method for the preparation of enantiomerically enriched epoxides. It allows for convenient configurational assignment of epoxides if the configuration of the corresponding allylic alcohol is known. Both enantiomers can be prepared using readily available enantiomeric diisopinocampheylboranes. 

Hydroboration of unsaturated azides is, in principle, a route to nitrogen heterocycles. The choice of dialkylboranes (R2BH) as hydroborating agents is crucial in order to avoid reduction of the azide group or the migration of the group R in the cyclic intermediate. 

Thexylchloroborane, prepared by the reaction of thexylborane with an equimolar amount of hydrogen chloride in ether ° or by hydroboration of 2,3-dimethyl-2-butene with BH2CI SMe2/ is a valuable reagent for the synthesis of mixed thexyl-n-dialkylboranes and for the reduction of cai boxylic acids to the corresponding aldehydes (see Section 4.10). 

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

The reduction-hydroboration of alkyldihalogenoboranes provides a more general approach to unsymmetrical dialkylboranes. The reduction of RBX2 (X = Br, Cl) with LiAlH followed by the addition of a terminal olefin gives RR BX. Redistribution does not occur, as proved by clean conversion of these dialkylhalogenoboranes into ketones via DCME reaction. However, if the olefin is present in the reaction mixture prior to the reduction, redistributed products are formed ... 

Transition state models 8 and 9 have been proposed for the formation of the major and minor products, respectively 5. For an experimental procedure for the reduction of a ketone with a dialkylborane, see Section 2.3.3.1.2.2.1 on alkyl-substituted cyclohexanones. 

Reduction in the latter case occurs by means of a dialkylborane species, but the overall products are the same as in the bimolecular process. However, the stereochemical outcome of these two processes may be very different. In the two-step process, the first step is rate determining since carbonyl reductions with dialkylboranes are generally very fast. The rate of reduction should then be independent of the carbonyl compounds structure or concentration. 

Scheme 7.4. Limiting mechanisms for carbonyl reduction of carbonyls by a trialkylborane (a) pericyclic mechanism, (b) Two step mechanism involving dehydroboration of a trialkylborane followed by carbonyl reduction by the resultant dialkylborane.

With hydride reagents such as dibal, Z-alkenes can be selectively obtained from alkynes in the phenolic lipid series (ref. 162), and related series of boron reagents greatly supplement the chemical methods of selective reduction and alkyiation. This selectivity has been achieved by the use of less reactive dialkylboranes such as bis(3-methyl-2-butyl)borane (di-isoamylborane), bis(2,3-dimethyl-2-butyl)borane (thexylborane), 9-boraUcyclo[3.kl]nonane (9-BBN) and dicyclohexylborane. Some applications in the polyethenoid field have been summarised (refs. 135,163) and the synthesis of alkenyl compounds generally reviewed (ref. 164). By the use of dibromoborane dimethylsulphide, an internal alkyne can be reduced selectively (ref. 165) as for example in the following way (R = n-alkyl). 

In this context, lipshutz et al. reported in 2000 a catalytic reductive aldol reaction of enones and aldehydes with [PhsPCuHjs (5 mol%) and PhMe2SiH (150mol%) [46]. The two-step reaction was carried out in one pot, without isolation of the intermediate sUyl enol ethers, efficiently providing the b-hydroxyketones in high yield. Lewis acids such as BF3 or TiCLj are used to promote the second step involving aldol reaction of the enol silane. In place of hydrosilanes, dialkylboranes could be employed as hydride sources, circumventing the need to introduce additional Lewis acids. Here, the aldol products are formed via intermediacy of the boron-enolates, with 5y -selectively for acychc enones and antz-selectively for cycHc enones [47-50]. 

The dialkylboranes and dialkylaluminums are also of value when partial reduction of an ester or amide is desired. The intermediates formed by the first hydride transfer are stable under the conditions of the reduction. Subsequent hydrolysis then provides the carbonyl compound at the aldehyde reduction stage. This method using diisobutylaluminum hydride has been particularly useful for reduction of esters to... 

The stereochemistry of reduction by dialkylboranes of ketones, including 2-methyl-cycloheptanone and 2-methylcyclo-octanone, has been surveyed. Invariably the dialkylboranes approach the ketone from the less hindered side to give the less stable alcohol product. The stereochemistry of reduction of 2-ethoxycarbonylcyclo-alkanones to 2-hydroxycycloalkane carboxylates with sodium borohydride and hydrogen-Raney nickel, have been compared. ... 

The monoalkyltrihydroborates may be regarded as convenient stabilized forms of monoal-kylboranes. Thus, treatment of the species with either HCl, CH3I, or (CH3)3SiCl, depending on the solvent required, in the presence of a substrate such as a hydroboration or reduction target, is a convenient way to effect such chemistry [2]. Similarly, dialkyldihydroborates are convenient sources of dialkylboranes and, thus, are useful precursors in typical dialkylborane chemistry [1, 2]. 

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