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. 98) 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 (1416, 1920, and 2122) while the shorter TDC [OSiR2CH2CHCH2] leads to a reversal in selectivity favoring the endo-re product (23a,b24a,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.