Darvon alcohol

The AE reactions on 2,5,5-trisubstituted allyl alcohols have received little attention, due in part the limited utility of the product epoxides. Selective ring opening of tetrasubstituted epoxides are difficult to achieve. Epoxide 39 was prepared using stoichiometric AE conditions and were subsequently elaborated to Darvon alcohol. Epoxides 40 and 41 were both prepared in good selectivity and subsequently utilized in the preparation of (-)-cuparene and the polyfunctoinal carotenoid peridinin, respectively. Scheme 1.6.12... 

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. 

Brinkmeyer and Kapoor (101) reported that the chiral hydride complex formed from LAH and (+ )-90 (Darvon alcohol) gave high enantiomeric ratios of chiral propargylic carbinols in the reduction of acetylenic ketones (Table 10, entries... 

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-... 

ASYMMETRIC REDUCTION, OF KETONES Darvon alcohol. NB-Enantrene. NB-Enantride. Lithium aluminum hydride-(S)-4-Anilino-3-methylamino-1 -butanol. B-3-Pinanyl-9-borabic y clo 13.3.1 Jnonane. 

Darvon alcohol [(+ )-(2S,3R)-4-(Dimethylamino)-3-methyl-1,2-diphenyl-2-butanol], 5, 231 8,184-185. 

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. 

One of the earliest attempts to do this used HAIH4 as the reducing agent and made it chiral by attaching Darvon alcohol to it. Unfortunately, this reagent is not very effective—successful substrates are confined to acetylenic alcohols, and even then the products are formed with a maximum of about 80% ee. 

Esters of Darvon alcohol" and its enantiomer are the drugs Darvon and Novrad (see p. 4Q3)—hence the ready availability ofthiS compound. 

Asymmetric reduction. The complex of L1A1H4, N-methylephedrine, and 3,5-dimethylphenol (1 1 2) reduces aryl alkyl ketones and a-acetylenic ketones to optically active alcohols with a purity of 75-90%. The optical yields are comparable to those observed with the structurally related darvon alcohol (8, 184-186). The reduction of benzoylacetylene, G HsCOC CH, results in a racemic alcohol. ... 

Table lists the results of the additions of both chiral and achiral alkoxytrialkylaluminates (20) to chiral a-keto esters (21). Some trends arc readily tqiparent (i) sodium is a superior cation as compared to lithium and potassium (entries 11-14) (ii) the configuration of the chiral moiety of the ester substrate dictates the facial preference (entries 1-7) and the preference follows the dictates of Prelog s rule (iii) there is an observable solvent effect with a preference for hexane/ether mixtures (iv) either (+)- or ( )-(2S,3/ )-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol (Darvon alcohol or (Zhirald) is the best of the... 

N-MethyIephedrine (+)-Darvon alcohol Et Ph (-)-Menthol Li Benzene/hexane 23 (R)... 

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