Use of Silicon-Based Tethers to Control Diastereofacial Selectivity in Azomethine Ylide Cycloadditions¹

A novel approach to controlling the diastereofacial selectivity of intramolecular dipolar cycloadditions of azomethine ylides (cf. 9 → 8) by varying the structure a silicon-based tether is described. A correlation is found between the length of the tether dipolarophile conjugate (TDC) and the observed sense of diastereocontrol. Azomethine ylides incorporating longer [OSiPh₂OCH₂CH₂OCOCHCH₂], [OSi(i-Pr)₂OSi(i-Pr)₂OCH₂CHCH₂], and [OSiPh₂OCH₂CHCH₂] TDCs favor endo-si attack (14 → 16, 19 → 20, and 21 → 22) while the shorter TDC [OSiR₂CH₂CHCH₂] leads to a reversal in selectivity favoring the endo-re product (23a,b → 24a,b). Structures of the cycloadducts have been assigned on the basis of selected X-ray diffraction data in combination with chemical/spectral correlation experiments. The work described herein represents a conceptually new approach to stereocontrol and extends the use of silicon-based tethers in asymmetric synthesis.