Henbest reduction

Henbest reduction. Reduction of the ketone (1) with chloroiridic acid and trimethyl phosphite resulted in a 73 % yield of the axial 3/9-aIcohol (2). Sodium borohydride... 

Henbest reduction. Under Henbest s conditions (1. 131-132), 3-ketosteroids are reduced predominantly to the axial alcohols that is, 3-keto-5a-steroids are... 

Henbest reduction (see Chloroiridic acid). Substitution of chloroiridic acid by tris(triphenylphosphine)chlororhodium results in even greater stereospecificity thus 5/3-androstane-3,17-dione is reduced to the 3/3-alcohol and 3 -alcohol in the ratio 50 1, with no detectable reduction of the 17-keto group. The reaction is preferably run in a sealed tube t 82°. 2-Ketosteroids are reduced entirely to the axial 2/3-alcohol (Henbest s conditions give 1% of the 2a-alcohol).1... 

Investigations of the Henbest reduction of ketones using chloroiridic acid and trimethyl phosphite in aqueous propan-2-ol have shown that the reduction is specific for 3-ketones in both the 5a- and 5 -series in the presence of 4-, 6-,... 

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

Pioneering studies on a different class of transfer hydrogenation catalysts were carried out by Henbest et al. in 1964 [15]. These authors reported the reduction of cyclohexanone (4) to cyclohexanol (5) in aqueous 2-propanol using chloroiridic acid (H2IrCl6) (6) as catalyst (Scheme 20.2). In the initial experiments, turnover frequencies (TOF) of 200 h 1 were reported. 

Henbest and co-worker 70 -702 used controlled amounts of lithium aluminum hydride -with success in the syntheda of steroid epoxides-Thue, 5j8t60-epoxides (Eq. 208), 90,110-epoxides (Eq. 207), and 110120 epoxide (Eq. 208) were obtainable by reduction of Ca-bromo-rt-os . Qa-bromo-U-uxo, and 12a-bromo-ll-oxo steroid precursors respec-... 

Henbest and Wdaon7 have examined carefully the products formed on the reduction of ds- and tram-1, 2- poxyr3-hy droxycyclo-hexane with lithium Aluminum hydride (Kqe. 386 and 390). The former... 

This method of preparing alcohols is an adaptation of an oxymercuration procedure of Sand and Genssler2 and reduction methods of Henbest and Nicholls.3 Other methods for preparing 1-methylcyclohexanol are oxymercuration followed by reduction in tetrahydrofuran-water 4 reaction of cyclohexanone with... 

Methyldecamine (174) was synthesized from pelletierine and the alkali-insoluble amide 170 by Hanaoka et al. (81). Decamine (18) was synthesized by Lantos et al. by the kinetically controlled condensation of pelletierine with biphenyl aldehyde (169) which afforded the cfs-quinolizidone (173) in 50% yield. Reduction of the carbonyl group with Henbest catalyst followed by alkaline hydrolysis produced the undesirable trans-fused quinolizidols as a major product. However, hydrogenation with platinium catalyst in an alkaline solution afforded the less stable cis-fused axial carbinol, which on cyclization followed by a mild basic hydrolysis yielded decamine (18). 

Henbest [ 4] has discussed a variety of reactions where the stereochemistry of the product is apparently controlled or influenced by the electrostatic effects of remote substituents. As an example, the isomer ratio of the steroid alcohols produced by reduction of a 12-keto function is sensitive to both the nature and configuration of a substituent at C(s) (p. 141). We may also cite the conversion of A -3-oxosteroids into their 4,5-epoxy-derivatives by alkaline hydrogen peroxide, where the proportion of /3-epoxy derivatives varies, according to substitution at C(iv>, from ca. 100% in the unsubstituted androst"4-en-3-one to 70% (- - 30% of a-epoxide) in the 17/ -hydroxy derivative. 

Einally may ba mantioned tha observation of HallsworUi and Henbest M that reduction of a -9a,lla-apoxy steroid vrith bthiuui iu ethylamine gave, in addition to the expected alcohol, a... 

Table 3 Wolff-Kishner Reduction of Carbonyl Hydrazones Using the Henbest Modification...

Henbest et al. used this reagent as catalyst in combination with aqueous isopropanol and trimethyl phosphite for the reduction of ketones the reaction mixture is refluxed for 1-5 days. The main reducing agent is the trivalent phosphorus species a little of the isopropanol is converted into acetone. The trimethyl phosphite... 

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