Boranes alcohols, synthesis

In the early work on the synthesis of prostaglandins, zinc borohydride was used for the reduction of the 15-ketone function and a 1 1 mixture of epimeric 15(S)- and 15(/ )-alcohols was generally obtained. Subsequent studies led to reaction conditions for highly selective reduction to the desired 15(S)-alcohol. Some of the results are summarized in the following table. The most practical method is E which utilizes borane as the stoichiometric reductant and a chiral, enzyme-like catalyst which is shown. 

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Since the discovery of the CBS catalyst system, many chiral //-amino alcohols have been prepared for the synthesis of new oxazoborolidine catalysts. Compounds 95 and 96 have been prepared93 from L-cysteine. Aziridine carbi-nols 97a and 97b have been prepared94 from L-serine and L-threonine, respectively. When applied in the catalytic borane reduction of prochiral ketones, good to excellent enantioselectivity can be attained (Schemes 6-42 and 6-43). 

The synthesis of chiral liquid-crystalline allenes was reported by Tschierske and co-workers (Scheme 4.10) [14]. An asymmetric reduction of 41 with Alpine borane was a key step to an enantioenriched allene 44. After removal of the silyl group, the allenic alcohol was etherified by the Mitsunobu method to give 45, the first liquid-crystalline allene derivatives. 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

Highly enantioenriched 4-alken-l-yn-3-ol moieties present in many bioactive acetylenic metabolites from sponges have been efficiently obtained by reduction of the parent 1-trimethylsilyI-4-alken-l-yn-3-one 18 with Alpine-borane or with BH3-SMe2 in the presence of chiral oxazaborolidines, followed by desilylation of the resulting alcohol. This strategy has been applied to the first stereoselective synthesis of petrofuran 19 <99SL429>. 

In addition to the results described, enantioselective access to 2-phosphino alcohols could be accomplished, too [71]. Starting from a borane-protected a-phosphino aldehyde hydrazone 91 as the key intermediate and available by two different approaches, the enantioselective synthesis of the desired 2-phosphino alcohols 93 could be accomplished. Thus, the electrophilic phosphinylation of aldehyde hydrazones 90 (via route I with the chlorodiphenylphosphine-borane adduct or via route II with chlorophosphines and subsequent phosphorus-boron bond formation) and the alkylation of phosphino acetaldehyde-SAMP hydrazones 92 (route III) was carried out (Scheme 1.1.26). 

Albert S.C. Chun of the Hong Kong Polytechnic University reports (J. Org. Chem. 68 1589, 2003) two important transformations. The three-component (Mannich) condensation of 10 with 11 and 12 proceeds with high diastereoselectivity, to give the amino alcohol 13. Hydroboration of the alkyne 14 followed by transmetalation of the intermediate vinyl borane gives a zinc species, which under catalysis by the easily-prepared 3-naphthol 13 adds to aromatic and branched aldehydes with high . The product allylic alcohols are useful intermediates for organic synthesis. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

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