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. <b>9</b> → <b>8</b>) by varying the structure a silicon-based tether is described. A correlation is found between the length of the <i>t</i>ether <i>d</i>ipolarophile <i>c</i>onjugate (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 (<b>14</b> → <b>16</b>, <b>19</b> → <b>20</b>, and <b>21</b> → <b>22</b>) while the shorter TDC [OSiR₂CH₂CHCH₂] leads to a reversal in selectivity favoring the endo-re product (<b>23a</b>,<b>b</b> → <b>24a</b>,<b>b</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.