Equatorial sulfur ylides

Stereoselective epoxidation can be realized through either substrate-controlled (e.g. 35 —> 36) or reagent-controlled approaches. A classic example is the epoxidation of 4-t-butylcyclohexanone. When sulfonium ylide 2 was utilized, the more reactive ylide irreversibly attacked the carbonyl from the axial direction to offer predominantly epoxide 37. When the less reactive sulfoxonium ylide 1 was used, the nucleophilic addition to the carbonyl was reversible, giving rise to the thermodynamically more stable, equatorially coupled betaine, which subsequently eliminated to deliver epoxide 38. Thus, stereoselective epoxidation was achieved from different mechanistic pathways taken by different sulfur ylides. In another case, reaction of aldehyde 38 with sulfonium ylide 2 only gave moderate stereoselectivity (41 40 = 1.5/1), whereas employment of sulfoxonium ylide 1 led to a ratio of 41 40 = 13/1. The best stereoselectivity was accomplished using aminosulfoxonium ylide 25, leading to a ratio of 41 40 = 30/1. For ketone 42, a complete reversal of stereochemistry was observed when it was treated with sulfoxonium ylide 1 and sulfonium ylide 2, respectively. ... 

Early efforts to probe the stereochemistry of sulfur ylide additions have been reviewed. Ylide (1) reacts with unhindered cyclohexanone derivatives to give products resulting from axial attack, whereas (2) gives rise to net equatorial addition. This is again due to the tendency of (1) to undergo l etically controlled reactions and (2) to give products resulting from thermodynamic control. However, equator attack may prevail even in kinetically controlled reactions if axial attack is rendered sufficiently hindered, e.g. by 1,3-diaxial interactions or by additional steric bulk adjacent to the reactive caibonyl. For example, the addition of (1) to ketone (9) afibrds the -epoxide shown in equation (6) exclusively. Other cyclic systems react with fairly predictable stereoselectivities in accord with the above observa-... 

Complexity is added to the study of this system by the ready functionalization of the sulfur atom by alkylation, oxidation and imination. 5-Alkylation to produce a compound such as (9) <76T1873) affords a system in which either of two possible chair conformers possesses an axial t-butyl group, and this system therefore exists preferentially in a twist conformation (10). Where no such conflicts occur the sulfur substituent adopts the equatorial position in a chair form. Inversion of configuration at sulfur in cyclic sulfides has been investigated in the system (11) (12) and the corresponding ylides (13) (14) (77JA2337). 

A single sulfonium ylide is beUeved to be formed as alkylation of oxathiane 3a gave the equatorial sulfonium salt exclusively [29]. Ylide conformation has been studied by X-ray, NMR, and computation [30]. All of these studies indicate that the preferred conformation of sulfur yUdes is one in which the filled orbital on the ylide carbon is orthogonal to the lone pair on sulfur. The barrier to rotation around the C-S bond of the semi-stabilized ylide, dimethylsulfonium fluorenide, has been found to be 42 1.0 kJmol [30]. This impHes that the ylide will adopt conformations 6a and 6b and that these will be in rapid equilibrium at room temperature. Of these two, conformation 6b will be favored as 6a suffers from... 

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