Development of a new molecular recognition chemistry using Lewis acidic receptors

分子识别化学的吸引力正在不断扩大，特别是作为模拟生物发生的化合物的主客体系统，这些化合物表现出酶等催化活性。Lehn教授和Cram教授发现了冠醚和密码及其包合体系，使他们成为诺贝尔奖获得者，而这些体系大多是由主客体分子之间的氢键网络构成的。与这些弱相互作用相比，Lewis酸性受体和Lewis碱之间相对较强的配位键在分子识别方面受到的关注较少，并且从未被用于选择性有机合成。在这种背景下，我们开发了几种具有空间位阻的酚氧化物配体的大体积有机铝试剂。这些体积庞大的铝试剂在溶液中是单体，因此具有很强的Lewis酸性，可以结合各种含杂原子的底物，如羰基、羧基和酰胺类化合物。这种络合反应有时是立体的、区域的和化学选择性的，导致选择性的有机反应，这是其他常见的Lewis酸如AlCl3、SnCl4、BF3和TiCl4所不能实现的。特别是三(2，6-二苯基苯氧铝(ATPH))最近被发现在几个反应中获得了前所未有的反应活性和选择性。1.碳负离子与α，β-不饱和醛的共轭加成2.外选择性的Diels-Alder反应3.立体和不对称Claisen重排4.1，6-与芳香族羰基底物的加成.

The fascination of molecular recognition chemistry is extending continuously, especially as host-guest systems which mimic biologically occurring compounds exhibiting catalytic activities like enzymes. The discovery of crown ethers and cryptands and their inclusion systems by Prof. Lehn and Cram led them to be the winners of the Nobel Prize, and most of these systems are constituted by hydrogen-bonding networks between host and guest molecules. Comparing with these weak interactions, relatively strong coordination bonding between Lewis acidic receptors and Lewis bases has received less attention for molecular recognition, and has never been used for selective organic synthesis.In this context, we have developed several bulky organoaluminum reagents which have sterically hindered phenoxide ligands. These bulky aluminum reagents are monomeric in solution, thereby possess strong Lewis acidity to bind a variety of heteroatom-containing substrates such as carbonyl, carboxyl and amide compounds. The complexation is sometimes stereo-, regio-, and chemoselective, leading to selective organic reactions which could not be realized with other ordinary Lewis acicls such as AlCl_3, SnCl_4, BF_3, and TiCl_4. In particular, aluminum tris(2,6-diphenylphenoxide(ATPH) was explored recently for obtaining unprecedented reactivity and selectivity n several reactions. 1. Conjugate addition of carbanions to alpha, beta-unsaturated aldehydes 2. Exo-selective Diels-Alder reactions 3. Stereo-and asymmetric Claisen rearrangement 4.1,6-Addition to aromatic carbonyl substrates.