Modified borane reagents

The milder metal hydnde reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodexnins reduce ketones to opucally active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc bromide-MMA. A -tetra-methylethylenediamme (TMEDA) reduces a,a-difluoro-[i-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The three isomers are formed on reduction with aluminum isopropoxide... 

The reactivity and selectivity of the borane reagent may be modified through the use of borane-Lewis base complexes. 

With these modified borane reagents, hydroboration-oxidation is an efficient method for converting a terminal alkyne into an aldehyde ... 

The tartrate ester modified allylboronates, the diisopropyl 2-allyl-l,3,2-dioxaborolane-4,5-di-carboxylates, are attractive reagents for organic synthesis owing to their ease of preparation and stability to storage71. In the best cases these reagents are about as enantioselective as the allyl(diisopinocampheyl)boranes (82-88% ee with unhindered aliphatic aldehydes), but with hindered aliphatic, aromatic, a,/l-unsaturated and many a- and /5-alkoxy-substituted aldehydes the enantioselectivity falls to 55-75% ee71a-b... 

Boranes have opened the door to asymmetric reduction of carbonyl compounds. The first attempt at modifying borane with a chiral ligand was reported by Fiaud and Kagan,75 who used amphetamine borane and desoxyephedrine borane to reduce acetophenone. The ee of the 1-phenyl ethanol obtained was quite low (<5%). A more successful borane-derived reagent, oxazaborolidine, was introduced by Hirao et al.76 in 1981 and was further improved by Itsuno and Corey.77 Today, this system can provide high stereoselectivity in the asymmetric reduction of carbonyl compounds, including alkyl ketones. 

Borane and aluminum hydrides modified by chiral diols or amino alcohols are well-known, effective reagents for the stoichiometric enan-tioselective reduction of prochiral ketones and related compounds (34). Reduction of prochiral aromatic ketones with the Itsuno reagent, which is prepared from a chiral, sterically congested /3-amino alcohol and borane, yields the corresponding secondary alcohols in 94-100% ee... 

Reduction of C=0 and C=N Bonds. Asymmetric reductions of prochiral ketones (19) to the corresponding chiral alcohols (20) using (S)-proline-modified borohydride reagents as the reductant have been published. The borane reductions of ketones (19) employing (S)-proline as chiral mediator proceeds with enantiomeric... 

Chiral modification is not limited to boronate and aluminate complexes. Boranes or alanes are partially decomposed with protic substances such as chiral amines, alcohols or amino alcohols to form useful reagents for enantioselective reduction of carbonyl compounds. For example, reduction of acetophenone with borane modified with the amines (65) to (67) gives (5)-l-phenylethyl alcohol with 3.5-20%... 

The first attempt to use a chiral ligand to modify borane was Kagan s attempt at enantioselective reduction of acetophenone using amphetamine-borane and desoxy-ephedrine-borane in 1969 [18]. However, both reagents afforded 1-phenyl ethanol in <5% ee. The most successful borane-derived reagents are oxazaborolidines, introduced by Hirao in 1981, developed by Itsuno, and further developed by Corey several years later (reviews [19,20]). Figure 7.2 illustrates several of the Hirao-Itsuno and Corey oxazaborolidines that have been evaluated to date. All of these examples are derived from amino acids by reduction or Grignard addition. Hirao... 

Reactions. - The reactions of diorganoiodophosphines with varying quantities of iodine have been studied by NMR techniques, which indicate the formation of a dialkyldi-iodophosphonium iodide as the initial product, followed by polyhalide anion formation in the presence of excess iodine. A modified McCormack synthesis of 3-silylated phosphol-3-enes (168) from phenyl-dichlorophosphine and 2-silylated 1,3-butadienes has been described. The reaction is carried out in the presence of a small amount of copper stearate in acetic anhydride at 50 °C, these conditions preventing the complete desilylation observed under standard conditions. The consecutive reaction of lithium phenylacetylide with triphenylborane and diphenylchlorophosphine results in the formation of the intramolecularly coordinated phosphino-borane (169). Treatment of the alkoxyvinyldichlorophosphines (170) with Grignard reagents... 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

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... 

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