EFFICIENT ENANTIOMER SYNTHESIS BY USE OF TOLERANT LEWIS ACID CATALYSTS : ASYMMETRIC CONJUGATE ADDITION REACTIONS

路易斯酸催化立体选择反应领域尚未解决的问题之一是开发耐受强配位亲核试剂的手性路易斯酸催化剂及其在有机合成中的应用。从这个角度，我们开发了多种4,6 -二苯并呋喃二基- 2,2′-双（4-苯并恶唑啉）的过渡金属配合物（R,R- dbfox /Ph）和铜（II）异丙基- 2,2′-双[4-（邻苯并恶唑啉）]的配合物（R,R- box /o-HOBn），并用于催化邻苯并羟胺、丙二腈和环1,3 -二酮的不对称共轭加成。得到了以下结果：羟胺的对映选择性共轭加成：R， R- box /o-HOBn的铜（II）配合物在o-苄基羟胺的共轭加成反应中作为一种有效的手性路易斯酸催化剂。在0.03 M的稀释条件下，在-40℃条件下，1-巴豆酰-3-异丙基-2-咪唑烷酮的对映选择性最高，达到97%。在β-位置上具有多种取代基的受体分子可以被成功地利用，这表明该反应被证明是有效和方便的获得β-氨基酸递送物的对映体。丙二腈的对映选择性共轭加成：2,2,6,6 -四甲基哌啶（TMP）催化量活化丙二腈与R， R- dbfox /Ph的镍（II）水络合物活化的3- crotonyl -2-恶唑烷酮反应，产生相应的Michael加合物，对映选择性高达94% ee。该反应为双活化型催化的不对称反应提供了第一个成功的例子，其中受体分子和供体分子都被刘易斯酸和碱催化剂分别激活。对映选择性环丁酮生成反应：研究发现，当催化量为2,2,6,6 -四甲基哌啶（TMP）活化的1,3 -环己二酮与R， R- dbfox /Ph的镍（II）水络合物活化的1-巴豆酰- 3,5 -二甲基焦唑反应时，相应的螺旋环丁酮的对映选择性高达96% ee。酸和碱两种催化剂都是必需的，吡唑受体对环丁酮的形成特别有效。少

One of the unsolved problems in the field of Lewis acid-catalyzed stereoselective reactions is the development of chiral Lewis acid catalysts which are tolerant to strongly coordinating nucleophiles and applications to organic synthesis. From this standpoint, we have developped a variety of transition metal complexes of 4, 6-dibenzofurandiyl-2, 2'-bis(4-phenyloxazoline)(R, R-DBFOX/Ph) and the copper(II) complex of isopropylidene-2, 2'-bis[4-(o-hydroxybenzyl)oxazoline] (R,R-BOX/o-HOBn) and utilized to the catalyzed asymmetric conjugate additions of O-benzylhydroxylamine, malononitrile, and cyclic 1, 3-diketones. The floowing results have been obtained.1. Enantioselective Conjugate Additions of a Hydroxylamine : The copper(II) complex of R, R-BOX/o-HOBn was found to act as an efficient chiral Lewis acid catalyst in conjugate addition reactions of O-benzylhydroxylamine. 1-Crotonoyl-3-isopropyl-2-imidazolidinone was the best acceptor which provided the maximum enantioselectivity up to 97% … More ee when the reaction was performed in a dilute condition (0.03 M) at -40℃. Acceptor molecules having a variety of substituents at β-position can be successfully employed showing that this reaction proves to be useful and convenient access to enantiomers of β-amino acid delivertives.2. Enantioselective Conjugate Additions of Malononitrile : In the reactions of malononitrile activated by a catalytic amount of 2, 2, 6, 6-tetramethylpiperidine (TMP) with 3-crotonoyl-2-oxazolidinone activated by the nickel(II) aqua complex of R, R-DBFOX/Ph, the corresponding Michael adduct was produced in enantioselectivities up to 94% ee. This reaction provides the first successful example for the double activation type catalyzed asymmetric reactions in which both of acceptor and donor molecules have been activated separately by Lewis acid and base catalysts.3. Enantioselective Cyclobutanone Formation Reactions : It has been found that, when 1, 3-cyclohexanedione activated by a catalytic amount of 2, 2, 6, 6-tetramethylpiperidine (TMP) was reacted with 1-crotonoyl-3, 5-dimethylpyrozole activated by the nickel(II) aqua complex of R, R-DBFOX/Ph, the corresponding spiro cyclobutanone is produced in enantioselectivities up to 96% ee. Both acid and base catalysts are essential and the pyrrazole acceptors are especially efficient for the formation of cyclobutanones. Less