THE DEVELOPMENT FOR STEREOSELECTIVE CONSTRUCTION OF FUSED HETEROCYCLES BY A NEW METHODOLOGY OF INTRAMOLECULAR HETERO DIELS-ALDER REACTION

稠合杂环的立体选择性结构是通过串联酯交换/分子内杂化Diels-Alder反应发展起来的，是一种新型的分子内杂化Diels-Alder反应。此外，利用含双恶唑啉的C2对称阳离子手性催化剂，实现了活性双齿烯酮与δ，ε不饱和醇的高对映选择性串联反应。1)甲氧基亚甲基乙酰丙酮、丁氧亚甲基氰基乙醛和(E)-4-甲氧基-2-氧代-3-丁烯酸甲酯等烷氧基取代的不饱和羰基化合物在δ，ε-烯醇存在下，在热条件下发生立体选择性分子内杂化Diels-Alder反应，得到相应的氢化吡喃。反应的关键步骤是烷氧基取代的不饱和羰基化合物与δ，ε-烯醇的酯交换反应。3)与E，Z-不饱和醇的反应是立体定向进行的，生成相应的加合物。(2)与仲醇和叔烷δ，ε-烯醇进行串联反应。4)在催化量的Lewis酸存在下，该串联反应在温和的条件下以立体选择性进行。5)该串联反应在一个烧瓶中进行。此外，在C2对称的(S，S)-叔丁基-双(恶唑啉基)铜(δ，ε)酸存在下，双齿烯酮如(E)-4-甲氧基-2-氧代-3-丁烯酸甲酯与SbF_3-醇的串联反应具有较高的对映选择性(ee>97%)，得到了相应的光学活性的氢吡喃。

The stereoselective construction of fused heterocycles was developed by tandem transetherification/intramolecular hetero Diels-Alder reaction as new type of intramolecular hetero Diels-Alder reaction. Furthermore the high enantioselective tandem reaction of activated bidentate enone with δ, ε-unsaturated alcohols was achieved by using cationic C2-symmetric chiral catalyst bearing bis(oxazoline). The following results were obtained.1) Alkoxy-substituted unsaturated carbonyl compounds such as methoxy-methyleneacetylacetone, butoxymethylenecyanoacetaldehyde, and methyl (E)-4-methoxy-2-oxo-3-butenoate, underwent stereoselective intramolecular hetero Diels-Alder reaction to afford corresponding hydropyranopyrans in the presence of δ, ε-alkenyl alcohols under thermal conditions. The reactions involve the transetherification process between alkoxy-substituted unsaturated carbonyl compounds and δ, ε-alkenyl alcohols as the key step. 2) These tandem reactions also proceeded with sec- and tert-δ, ε-alkenyl alcohols 3) With E, Z-unsaturated alcohols, the reaction proceed stereospecificly to provide correspoding adducts. 4) This tandem reaction proceeds stereoselectively under mild conditions in the presence of catalytic amount of Lewis acid. 5) This tandem reaction proceed in one flask. Furthermore the tandem reaction of bidentate enone such as methyl (E)-4-methoxy-2-oxo-3-butenoate with δ, ε-alkenyl alcohols proceeds in high enantioselectivity (over 97% ee) to afford corresponding optically active hydropyranopyrans in the presence of C2-symmetric (S,S)-tert-butyl-bis (oxazolynyl) Cu (SbF6) 2 as chiral Lewis acid.