Trialkylborohydride

Sodium or tetramethylammonium triacetoxyborohydride has become the reagent of choice for diastereoselective reduction of P-hydroxyketones to antidiols. Trialkylborohydrides, eg, alkaH metal tri-j -butylborohydrides, show outstanding stereoselectivity in ketone reductions (39). 

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

The hydride-donor class of reductants has not yet been successfully paired with enantioselective catalysts. However, a number of chiral reagents that are used in stoichiometric quantity can effect enantioselective reduction of acetophenone and other prochiral ketones. One class of reagents consists of derivatives of LiAlH4 in which some of die hydrides have been replaced by chiral ligands. Section C of Scheme 2.13 shows some examples where chiral diols or amino alcohols have been introduced. Another type of reagent represented in Scheme 2.13 is chiral trialkylborohydrides. Chiral boranes are quite readily available (see Section 4.9 in Part B) and easily converted to borohydrides. 

Litkiam trialkylborohydrides. The reaction of r-butyllithium with trialkyl-boranes provides a convenient route to lithium trialkylborohydrides.- ... 

The involvement of trialkylboranes in these reactions was probed by use of the optically active trialkylborohydride 52, shown in Eq. (16) (59). In previous work, 52 had been demonstrated to reduce the prochiral ketone acetophenone to 1-phenylethanol of 17% optical purity (80). Compound 52 was then used to generate the unstable anionic formyls 6, 12, and 26 (Table I) subsequently, acetophenone was added to these reaction mixtures. If Eq. (16) were reversible and 52 were the active hydride transfer agent, 1-phenylethanol of 17% optical purity would be expected. In practice, optical purities of 3.1-11.7% were obtained (39). This indicates some type of trialkylborane involvement in the hydride transfer (the exact role cannot be readily determined by experiment). Therefore, it became important to attempt similar reactions with isolable, purified formyl complexes. 

Lithium trialkylborohydridesr Trialkylboranes react rapidly with lithium aluminum hydride in ether in the presence of DABCO to form trialkylborohydrides and aluminum hydride, which is precipitated as a complex with DABCO. The method is suitable for preparation of even highly hindered complex hydrides. Yields are quantitative. 

Selective reductions. As expected, this dialkylborohydride shows reducing properties intermediate between those of the mild lithium borohydride and of the powerful lithium trialkylborohydrides. As a result, it is particularly useful for selective reductions. 

Reactions with organometalllc substrates. One useful reaction of this and other trialkylborohydrides is cleavage of metal carbonyl dimers to metal carbonyl anions (equation I). The by-products are Hj and B(C2Hs)3. Another useful reaction is the generation of anionic formyl complexes (equation II). Sulfur (Sg) can be cleaved to give either LijS or Li2S2 (equations III and IV). Disulfides are cleaved by this reaction to lithium mercaptides. 

Lithium naphthalenide, 284-285 Lithium phenylthio(trimethylstannyl)-cuprate, 330 Lithium phthalide, 285 Lithium 2,2,6,6-tetramethylpiperidide, 145, 281,285-286, 362 Lithium trialkylborohydrides, 278 Lithium triethylborohydride, 286 Lithium tricthylborohydride-Aluminum t-butoxide, 287 Lycorine, 503... 

Borohydride Reagent. Treatment of NB-enantrane with t-Butyllithium provides the lithium trialkylborohydride NB-Enantride (eq 4). This reagent is an effective asymmetric reducing agent for acetophenone and alkyl methyl ketones such as 2-octanone (eq 5). Few reagents show selectivity for such alkyl ketones. 

Stereoselectixe reduction of ketones. Corey s synthesis of prostaglandins utilizes as a key intermediate the cnone (I). One major synthetic problem is the stereoselective reduction of the carbonyl group to the desired 15S alcohol (Ila). Reduction with various borohydridc reagents or various trialkylborohydrides (R, R2R3BH Li ) affords about... 

Trialkylborohydride reducing agents differ from borohydride in their ability to transfer hydride directly to a carbonyl ligand without prior substitution in the coordination sphere. They are used to synthesize formyl complexes " . When formyl complexes lose CO and undergo hydride migration from the formyl ligand to the metal, a transition-metal hydride results. The process is formally similar to nucleophilic attack by [OH] on a carbonyl ligand, followed by loss of CO and formation of a transition-metal hydride. Examples of hydride syntheses via formyl complexes are ... 

Gp2TiCl2/NaBH4 mixtures have been studied as a convenient system for the hydroboration of alkenes. Mechanistic studies for these reactions are reported. These processes provide different regioselectivities and are catalyzed by the isolated Cp2Ti(/x-H)2BEl2 species. Lithium borohydride appears to be involved in the formation of the true catalytically active complex. Extensive nB NMR experiments indicated that the predominant products in the hydroboration reaction of Ph-CH=CH2 are a regiomeric mixture of tetraalkylborates, with minor amounts of trialkylborohydrides.1624,1625... 

Alkyl- or 2-aryl-substituted allyl halides 1, when treated first with a borane and then with a base, give substituted cyclopropanes in moderate to excellent yield. For the hydroboration step tetraalkyldiboranes 2 (method A) are superior to diborane (B2H ) itself (methods B or C, respectively), and sodium tetraalkylborates 4a or trialkylborohydrides 4b are preferred bases. 

Numerous data have been recorded concerning the stereochemistry of the reduction of the substituted cyclohexanone derivatives, and in general, preferential axial attack occurs with LiAIH, derivatives, whereas equatorial attack takes place for trialkylborohydrides. This tendency is valid for this case and it is noteworthy that (IS, 3R)-3-(/ -tert-butylphenylthio)cyclohexanol is obtained almost exclusively by employing LiAlH(OBu )3 (entry 9). Thus, the 3-arylthio asymmetric center is effectively transferred to C-1, producing both configurational isomers (R and S) by suitable choice of reducing reagent. 

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