Sn2 inversion

Sn2 inversion of an alcohol by a nucleophile using diethyl azodicarboxylate (DEAD) and triphenylphosphine. 

Trimethylorthoformate forms a stabilized dioxocarbenium ion which activates the lactone towards attack by methanol with Sn2 inversion at the methyl-substituted carbon. 

The selenoglycosides were also found to be transformed into the glycosyl fluorides using 4-methyl(difluoroiodo)benzene via an Sn2 inversion of the anomeric centers (O Scheme 16) [50]. 

Regiospecific opening of the epoxide was also achieved by intramolecular delivery of the nucleophile. The alcohol 52 was converted into the reactive intermediate 53 with methyl isocyanate. Cyclisation can occur only to the nearer end of the epoxide (5-exo-tet) to give 54. The stereochemistry is already correct for the SN2 inversion on the epoxide 53. The free OH group is turned into a good leaving group by mesylation without isolation of 54. 

The leaving group X in (23) will be derived from a hydroxyl group as usual. Hence (24) could be made from the symmetrical epoxide (25) choosing the correct stereochemistry to give (24) by Sn2 inversion. The required stereochemistry is cis so that we can make (24) from the readily available acetylenic diol (26) by simple steps. 

Two successive Sn2 inversion steps are necessary to give the desired net result of stereochemical retention ... 

E2 anti elimination on A can lead to only one alkene B via removal of the circled hydrogen. Conversion to the iodo-derivative via Sn2 inversion allows cither of the two circled hydrogens to be removed in anti elimination, leading to a mixture of alkenes B and C. 

In a retrosynthetic sense, breaking the cyclopentene-aryl bond seemed very attractive, forming two roughly equal halves of die molecule. Compounds 14 and 15 could be joined synthetically using a cross coupling reaction where X is a halide or triflate and M is a metal such as boron or zinc. Protected hydroxylamino-cyclopentene 15 could arise from Sn2 inversion of chiral cyclopentenol 16, which in turn could be formed by chiral reduction (or achiral reduction/resolution) of 3-substituted cyclopentenone 17. The development of a new route based on this retrosynthetic analysis is described below. 

Having prepared S-CH3CH2CHICH3 with high enantiomeric purity, one can subsequently perform a second, clean Sn2 inversion using ammonia as the nucleophile in, preferably, a polar aprotic solvent such as an ether to arrive at the desired product. 

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