Henbest epoxidation

Henbest Epoxidation- epoxidation directed by a polar group... 

The boron trifluoride-ether complex has been employed mainly in the opening of 5,6-epoxides. This reaction was first studied by Henbest and Wrigley and affords products depending on the nature and stereochemistry of the... 

Henbest and Jackson have rationalized these remote directive effects on the basis of the well-supported mechanism of alkaline epoxidations. The initial step in the reaction is the reversible addition of the hydroperoxide ion... 

On the other hand, H.B. Henbest realised that adjacent polar functional groups have a directing effect on the epoxidation of alkenes as well as on other related reactions [2]. A very well known example is the 5yn-directing effect of an ally lie hydroxyl group in epoxidations of cyclic alkenes (Scheme 10.1) ... 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

In 1957, Henbest and Wilson reported hydroxyl-directed epoxidation using m-chloroperoxybenzoic acid (mCPBA) [3]. In the synthetic studies of juvenile... 

Normally, additions depicted by model C lead to the highest asymmetric induction. The antiperiplanar effect of OR substituents can be very efficient in the Houk model B ( , , , , ) however it plays no role in model C. Furthermore, the Houk model B must be considered in all cycloaddition-like reactions. The Felkin-Anh model A is operative for nucleophilic additions other than cuprate additions ( ). The epoxidation reactions are unique as they demonstrate the activation of one diastereoface by a hydroxy group which forms a hydrogen bridge to the reagent ( Henbest phenomenon ). The stereochemical outcome may thus be interpreted in terms of the reactive conformations 1 and 2 where the hydroxy function is perpendicular to the olefinic plane and has an optimal activating effect. 

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-... 

In the steroid field, Henbest and Wrigley18 - have examined a number of epoxides with reference to boron trifluoride, which is a much stronger Lewis add than magnesium bromide and hence requires much milder operating temperatures. In all instances studied, hydride shifts look place in preference to ring contraction. The product stereochemistry indicated unequivocally a Walden inversion at the site of... 

Particularly interesting observations were made by Henbest and Wrig1eyMi for fc,6 - and 50,60-epoxy steroids variously substituted at C 8), isomerization to 0-oxo steroids taking place smoothly. Rearrangement of the 5 ,6 -epoxide is somewhat slower, presumably because of... 

In 1967, Henbest et al. reported the first asymmetric epoxidation with an optically active peracid as the chiral oxidant [3], Since then, many optically active peracids have been used for this purpose but enantioselectivity remains low (<20% ee). This is probably because the substrate and the asymmetric center in the peracid are distant from each other in the transition state of the epoxidation as shown in Figure 6B.1 [4],... 

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. 

The first mechanism, with one small refinement, e lains factorily the neighboring-group effect discussed above. The transj1iu i state for allylic epoxidation is represented by Henbest and Wilson. by Albrecht and Tamm.t and also by Sa siver and English, t shown in Eq. (41)... 

Extending their inveetigatione into the steroid field, Henbest and Witsoo noted that choleat-l-ene gave an a-epoxide, whereas 3j9 bydroxycholeat-l-ene yielded the oenreeponding -epoxy steroid (Eq. N). Their observation was supported independently by Albrecht and in other work. 

The method employed by Law, et al. to obtain Ad-disubstituted ISQs [87] was a modification of the approaches of Henbest [88], Huffman [89] and Nelson [90] (Scheme 8). Epoxidation of commercially available methyl-3-cyclohexene-1-carboxylate (80) with m-CPBA yielded a mixture of epoxides (81a and 81b), which were then opened with various amines producing the isomeric amino alcohols (82a and 82b). Only isomer 82a is capable of undergoing cyclization to the... 

H. B. Henbest, R. A. I. Wilson, Aspects of stereochemistry. I. Stereospecificity in formation of epoxides from cyclic allylic alcohols, /. Clteni. Soc. (1957) 1958. 

The standard situation is well illustrated by Henbest s classical epoxidation of 2-cyclohexenol withMCPBA [reaction (23),Scheme 10] [25].TheOH-functionacts... 

Reduction of epoxides. Hallsworth and Henbest (1,579,refs. 12 and 13)found that some steroidal epoxides, which were unreactive to lithium aluminum hydride, are easily reduced with a large excess of lithium in ethylamine. However, some olefin is also formed in some cases. Brown et al.1 now report that the combination of lithium and ethylenediamine at 50° is excellent for reduction of labile epoxides of bicyclic ketones, which are reduced only slowly by lithium aluminum hydride and usually with some extensive rearrangement. They chose ethylenediamine rather than ethylamine because the reduction is less vigorous in ethylenediamine than in ethylamine and thus easier to control. Also isolation of the alcohol is simplified because ethylenediamine is very soluble in water and only slightly soluble in ether, whereas ethylamine is miscible both in water and in ether. By this procedure, norbomene oxide (1) is reduced to pure ejco-norbomanol (2) in 87% yield (isolation). Analysis by glpc indicated that two rearranged alcohols (3, 4) are formed to a minor extent and that (2) is formed in 99.3% yield. 

Sable and coworkers also synthesized all four of the predicted racemic forms of cyclopentanetetrol (131-134), and the meso diastereomer (130). The all-cfs, meso isomer is unknown. cis-Hydroxylation of the enediols (136 and 137) is effected with permanganate or with silver chlorate-osmium tetroxide Irans-hydroxylation is caused by peroxybenzoic acid. Ihe epoxy group enters ds to the neighboring, free hydroxyl group in the intermediates (136-A, 136-B, and 137-A), according to Henbest s rule. However, prior reaction of the diol structure in the intermediate (136-A) with acetone caused the epoxide group to enter trana,... 

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