Asymmetric Synthesis of All Eight Seven-Carbon Dipropionate Stereotetrads
2007-07-25T00:00:00Z (GMT) by
Enantiopure cycloheptadienyl sulfones <b>6</b> and <b>7</b> are diastereoselectively epoxidized to yield epoxyvinyl sulfones <b>8</b>, <b>9</b>, <b>14</b>, and <b>16</b> in high yields and diastereomeric ratios. Syn and anti methylation of epoxides <b>8</b>, <b>9</b>, <b>14</b>, and <b>16</b> enables access to all eight possible diastereomeric stereotetrads, seven of which are commonly found in polypropionate natural products. Anti methylations of the above epoxides are possible by either the reaction of methyl organometallics promoted by copper(I), or via reaction with trimethylaluminum to yield stereotetrads <b>11</b>, <b>12</b>, <b>22</b>, and <b>24</b>. Syn methylations are achieved via Lawton S<sub>N</sub>2‘ reaction in the case of stereotetrads <b>10, 15</b>, and <b>38</b>, while stereotetrad <b>13</b> is accessed by an oxidation/reduction alcohol inversion sequence from stereotetrad <b>11</b>. All stereotetrads were obtained in high diastereomeric ratios and yields, and their relative stereochemistry was confirmed by X-ray crystallography. Oxidative cleavage of the cyclic stereotetrads yields termini-differentiated acyclic heptanyl stereotetrads ready for use in building larger fragments in the course of target syntheses.