Use of silicon-based tethers to control diastereofacial selectivity in azomethine ylide cycloadditions

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 [OSiPh(2)OCH(2)CH(2)OCOCH=CH2], [OSi(i-Pr)(2)OSi(i-Pr)(2)OCH2CH=CH2], and [OSiPh(2)OCH(2)CH=CH2] TDCs favor endo-si attack (14 --> 16, 19 --> 20, and 21 --> 22) while the shorter TDC [OSiR(2)CH(2)CH=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.