Chiral borane-involving reactions

There are a number of different approaches to performing enantioselective reductions of ketones within the flow domain, using either a borane-derived hydride transfer agent such as that described previously or modified transition metal hydrogenations an example of the latter involved a column of Pt/Al203 modified with O-methyl cinchonidine (21) to induce chirality in the product (Scheme 4.64). Continuous monitoring showed that a 30 min induction period was required before the optimal reaction rate and ee could be obtained. This was ascribed to the need for... 

The synthesis of various new chiral (o-hydroxyaryl)oxazaphospholidine oxides (139), derived from (S)-proline derivatives, from precursors (140) have been elaborated. This two-step reaction involves an unstable metallated intermediate that undergoes a fast 1,3-rearrangement with the formation of phosphorus-carbon bond. These catalysts have been successfully applied to the catalytic asymmetric borane reduction of numerous prochiral ketones with enantiomeric excess up to 84% ee (Scheme 35). ... 

The reaction of a chiral alkene with borane in the proper stoichiometry may afford alkyl boranes R BH2 or dialkyl boranes R BH, where R is a chiral ligand. Attempts to achieve highly selective reductions of ketones using such reagents have met with little success, however. Trialkyl boranes R3B were first reported to reduce aldehydes and ketones (under forcing conditions) in 1966 by Mikhailov [50]. Mechanistic studies (summarized in ref. [46]) showed that there are two limiting mechanisms for the reduction of a carbonyl compound by a trialkylborane, as shown in Scheme 7.4 a pericyclic process reminiscent of the Meerwein-Pondorf-Verley reaction (Scheme 7.4a), and a two step process that involves dehydro-... 

The reaction involves the coordination of a nitrogen atom to borane, the carbonyl group to the endocyclic boron atom and subsequent hydride transfer and decomposition of the alkoxyborane intermediate to the chiral alcohol. 

Deprotonation of t-Bu-BisP (BH3)2 with 1.2 equivalents of s-BuLi/( )-sparteine formed a mixture of mono- and dilithiated t-Bu-BisP (BH3)2 whose - intermolecular oxidative coupling with Cu(II) afforded a mixture of tetraphosphine borane 86 and hexaphosphine borane 87. The use of ( )-sparteine may surprise the reader, as the reaction does not involve any enantioselective deprotonation. However, it was found that its presence was beneficial to activate the -BuLi, showing that ( )-sp is not only a chiral inductor, but also modifies the reactivity of the organolithium reagents. After separation by column chromatography, 86 and 87 were obtained in 26% and 14% isolated yields respectively. Tetraphosphine borane 86 was subjected to similar reactions, affording compounds 88 (29% yield) and 90 (8% yield), which contain 8... 

Hydroxy-esters. - Once again, most contributions to this area involve the synthesis of chiral hydroxy-esters. Almost complete enantioselectivity is achieved in the reduction of a-keto-esters to a-hydroxy-esters using Alpine-Borane (B-(3-pinanyl)-9-BBN) derived from either (+)- or (-)-a-pinene when the reactions are carried out at relatively high concentrations (>2M). Many other types of prochiral ketones are also reduced with excellent asymmetric inductions although 3-keto-esters may not be particularly suitable substrates as ethyl acetoacetate is reduced to ethyl 3-hydroxybutanoate with an enantiomeric excess of only... 

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