Development of Enantiselective Radical Reactions

鉴于手性配位剂不对称合成的最新进展，我们一直在探索由手性配位剂引发的各种自由基反应。[1，2]-With重排在t-BuLi存在下手性双恶唑啉[(S，S)-盒-i-Pr(2)]的催化下，生成了[1，2]-重排产物苯甲醇3。这是第一个对映体选择性[1，2]-Witing重排的例子。接下来，我们还研究了当前重排的不对称催化版本。因此，在相同的条件下，用10mol%的(S，S)-2和2当量的t-BuLi进行1的重排。正如预期的那样，以相对较高的ee和化学产率(60%ee，86%)获得了醇(S)-3。此外，以外消旋乙醚为原料，通过对映体选择性合成叔醇(最高可达65%ee)，证明了[1，2]-With重排反应的合成潜力。这是史蒂文斯重排的对映选择性版本的第一个例子。

In view of the recent progress in the chiral coordinating agent-based asymmetric synthesis, we have been exploring the various radical reactions induced by the chiral coordinating agent-based protocol. Disclosed herein are the enantioselective[1,2]-Witting rearrangement via the asymmetric lithiation with RLi/chiral bisoxazoline and Stevens rearrangement with chiral alkoxides.Enantioselective[1,2]-Witting RearrangementThe carbanion-radical rearrangement of dibenzyl ether(1), when induced with t-BuLi in the presence of chiral bisoxazoline[(S,S)-Box-i-Pr(2)], was found to afford the [1,2]-rearrangement product, benzyl alcohol 3 in 63% ee. This represents the first example of an enantioselective[1,2]-Witting rearrangement. Next, we also examined the asymmetric catalytic version of the present rearrangement. Thus, the rearrangement of 1 was carried out using 10 mol% of(S,S)-2, and 2 equiv of t-BuLi under the same conditions. As anticipated , alcohol(S)-3 was obtained in comparably high %ee and chemical yield(60% ee, 86%). Furthermore, the synthetic potential of the enantioselective[1,2]-Witting rearrangement has been demonstrated by the enantioselective synthesis of tertiary alcohols(up to 65% ee)from racemic ethers.Enantioselective Stevens RearrangementBenzyldimethylamine derived ammonium salt(racemic)was treated with suger derived chiral alkoxide to afford the enantio-enriched rearrangement product in 38% ee. This is the first example of the enantioselective version of Stevens rearrangement.