Metalated 2-Alkenylsulfoximines:  Efficient Solutions for Asymmetric d3-Synthons

By starting from the 4,5-dihydro-1,2λ6,3-oxathiazole 2-oxides 5 and 6 or their enantiomers, a number of enantiopure acyclic and cyclic 2-alkenyl sulfoximines have been prepared. After deprotonation with n-BuLi and transmetalation with chlorotris(isopropoxy)titanium chloride, these sulfoximines can be γ-hydroxyalkylated to the corresponding γ-hydroxy vinyl sulfoximines with high diastereomeric excesses (≥95% de) irrespective of the nature of the added aldehyde. The cyclopentenyl- and cyclohexenylsulfoximines 50a/51a and 50b/51b are demonstrated as the first examples of highly enantioselective solutions for cyclic d3-synthons. From the X-ray structures of 18e, 21, 59, and 62, it can be deduced that the S S/R S-configured sulfoximines attack the aldehydes nearly exclusively from their Re/Si faces, respectively. A remarkable property of these systems is that this stereochemical interrelation holds also for reactions with chiral aldehydes (reagent control), although here the achievable stereocontrol depends on the relative configuration of the stereogenic centers in the auxiliary. This is especially true for the cyclohexenylsulfoximines 50b and 51b, which require the same absolute configuration at both the sulfur atom and the carbon atom in the side chain of the amino acid based auxiliary. In the case of this intramolecular matched situation, the stereochemical preferences of the chiral aldehyde can be overcompensated nearly completely. This mutual reinforcement of the two stereogenic centers in the sulfoximine moiety accounts for the high degree of reagent control (≥94% de in the acyclic series, ≥95% de with the five-membered ring systems, and ≥97% de with the cyclohexenylsulfoximines) achievable with these 2-alkenylsulfoximines.