藉由Morita-Baylis-Hillman反應發展出串聯式三組分反應及其應用於多官能基α,β-不飽和酮類之合成

Abstract

Morita-Baylis-Hillman 產物可藉由β-碳上羥基活化羰基，因此為一個很好的Michael accepter。本實驗室發展出一個具有高度選擇性的三組分反應，利用單一步驟的一鍋化反應，藉由不同芳香族醛類57、高活性的烯類22或37及醯胺67或78在EtPPh2或PPh3的催化下成功的合成一具有多官能基的三組分產物，產率為41-97%。其反應機構是先進行Morita-Baylis-Hillman反應，接著在不需另外加入其他的鹼的條件下，被去質子化的親核性試劑會對Morita-Baylis-Hillman 產物進行Michael加成反應，生成碳-氮鍵後即得到產物。另外，我們也發展出利用57、37及78為反應物，經由EtPPh2或PPh3的催化進行此一鍋化的三組分反應，且不需進行純化，可直接進行醯化反應和消去反應，以合成α,β-不飽和酮類，所得產率為35-83%，並且具有很好的立體選擇性(E/Z = 95/5-90/10)。 The Morita-Baylis-Hillman reaction adduct, starting from actived alkene and aldehyde, is a good Michael accepter according to the ester or ketone function activated by the neighboring hydroxy group. We have developed a general procedure for a new type of chemoselective three-component reaction with aromatic aldehyde 57, activated alkenes 22 or 37 and amide 67 or 78 catalyzed by EtPPh2 or PPh3. The reaction mechanism is proposed to undergo the Morita-Baylis-Hillman reaction followed by Michael addition of nucleophiles toward the Morita-Baylis-Hillman adduct. To the best of our knowledge, there are no reports of successful reactions or related studies that utilize this strategy. The reaction condition is very mild, and numerous highly functional three-component adducts in 41-97% yield. In addition, we have developed one-pot procedure for the syntheses of polyfunctional α,β-unsaturated ketones via our designed three-component reactions and acylation of the corresponding adducts followed by elmination. The reaction can be efficiently afforded in 35-83% yields with high stereoselectivities (E/Z = 95/5-90/10).