Reduction using DARVON

Using Darvon alcohol as modifier, acetylenic ketones are reduced to acetylenic alcohols with up to 85% ee62. The reduction does not seem to be directed by steric effects since the acetylenic unit behaves similarly to a phenyl group. 

Taking a lead later from the work of Brinkmeyer and Kapoor, several amino alcohols have been exploited for the asymmetric reduction of alkynones. One such publication appeared from the group of Cohen, who have also used Darvon alcohol-LAH complex at 70°C to furnish various propargyl alcohols in 34 to 90% e.e. In addition to Darvon alcohol, other chiral ligands were explored (Table 21.2). 

Optically active 1-alkoxyallylstannanes are more readily available by asymmetric reduction of acylstannanes using either ( + )-(/J)-BINAL-Il105 106 or LiAlH4-Darvon alcohol [(2S,3/ )-4-dimethylamino-3-mcthy]-1,2-diphenyl-2-butanol] 06 followed by O-alkylation. The stereoselectivity of the BINAL-H reductions differs from that usually observed, and has been attributed to a tin-oxygen hypervalent interaction107, l08. 

The Darvon alcohol-LAH complex was used in the reduction of the acetylenic ketone (93) in one step of an asymmetric total synthesis of lla-hydroxypro-gesterone (97), a key intermediate in the production of hydrocortisone acetate... 

Asymmetric reductions. Hoffmann-LaRoche chemists1 have examined in detail the asymmetric reduction of a,/Nacetylenic ketones with Darvon alcohol (I) and related alcohols. Use of the enantiomer of 1 resulted predominately in reduction to the enantiomer (S) of the (R)-carhinols obtained with I. Several optically pure 1,3-... 

Chiral 1,2-aminodiols. Morrison el al.1 have prepared five chiral 1,2-aminodiols related to Darvon alcohol. The only useful one for asymmetric reduction of ketones in conjunction with LiAlH4 is 1, prepared from (S)-propylene oxide and (S)-ot-methylbenzylamine. Acetophenone and propiophenone are reduced by LiAlH4-l to the corresponding (R)-alcohols in 77-82% ee. In this case, the three (S)-centers reinforce one other. 

In 1983 we developed a synthesis of (R)-87 without recourse to the Wittig reaction.62 Figure 4.33 summarizes our synthesis. Asymmetric reduction of keto ester A with lithium aluminum hydride in the presence of Darvon alcohol B furnished hydroxy ester C of moderate enantiomeric purity (78.6% ee). Recrystallization of D was the successful way to enrich its enantiomeric purity. Accordingly, the hydroxy ester C was hydrolysed, and the resulting acid was treated with (R)-(+)-l-(l-naphthyl)ethylamine to give D, which was recrystallized from acetonitrile to furnish the pure salt D. Acidification of D was followed by the Lindlar hydrogenation to give enantiomerically pure (R)-87. This process was once used for the commercial production of (R)-87. 

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