Dihydroxylations acyclic diastereoselectivity

Sulfoxide groups direct the dihydroxylation of a remote double bond in an acyclic system perhaps by prior complexation of the sulfoxide oxygen with osmium tetroxide (eqs 16 and 17). Chiral sulfoximine-directed diastereoselective osmylation of cy-cloalkenes has been used for the synthesis of optically pure di-hydroxycycloalkanones (eq 18). Nitro groups also direct the osmylation of certain cycloalkenes, resulting in dihydroxylation from the more hindered side of the ring. In contrast, without the nitro group the dihydroxylation proceeds from the less hindered side (eq 19). ... 

Kishi has conducted a comprehensive series of investigations on acyclic stereocontrol in OsO,-catalyzed dihydroxylation of allylic alcohols and ethers [191, 195). These studies were prompted by the synthetic problems presented by one of the most complex polyketides synthesized to date palytoxin [196], The observed stereoselectivity trends in dihydroxylations of allylic substrates such as 265 and 268 led Kishi to propose the empirical model 271 for predicting the diastereoselectivity (Scheme 9.34) [191, 195]. In this model, minimization both of A 1,3 strain and of electrostatic repulsions between 0s=0 and the ether oxygen (cf. 266 and 269) are believed to lead to predominant formation of the 1,2-anti products 267 and 270, respectively. 

Other empirical models for the prediction of the diastereoselectivity in dihydroxylation reactions of acyclic substrates have been proposed. Thus, the dihydroxylation of certain y-hydroxy-a,j3-unsaturated esters led Stork to suggest the inside alkoxy" model 273 (Scheme 9.35) [197]. The results observed by Stork in the dihydroxylation of (E)-enoate 272 are in good agreement with Houk s related inside alkoxy model for diastereoselective reactions of acyclic substrates [198]. However, for (2)-isomer 276 the overriding consideration are A, 3 interactions, and thus Stork hypothesized that in the reactive conformation 277, the allylic hydrogen is eclipsed with C=C, leading to dihydroxy-lated lactone 279. 

As is apparent from the preceding discussion, a full understanding of the observed diastereoselectivity in dihydroxylation reactions of acyclic allylic alcohols remains elusive. Thus, the use of any one model is insufficient, and a careful analysis of the steric and electronic particulars of a given substrate must be conducted. Nevertheless, an impressive number of diastereoselec-tive dihydroxylations of acyclic olefins in complex molecule synthesis attest to the central role of this transformation [42, 43], Selected examples of stereodivergent dihydroxylations reported by Danishefsky are showcased in Schemes 9.36 and 9.37 [201]. Dihydroxylation of ( )- and (Z)-unsaturated esters 287 and 290, respectively, thus proceeded with excellent diastereoselectivity. Danishefsky has proposed a transition state model based on the ground state conformations of the starting materials as determined by X-ray analysis. The dihydroxylations were thus postulated to occur from the sterically less hindered faces of the olefins, as depicted in 288 and 291. Diol 292 was subsequently converted into N-acetylneuraminic acid (293). 

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