Development of a new molecular recognition chemistry using Lewis acidic receptors

分子识别化学的魅力正在不断扩展，特别是作为模拟生物发生的化合物表现出催化活性的主客系统，如酶。Lehn和Cram教授发现的冠醚和隐醚及其包合体系使他们获得了诺贝尔奖，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酸受体与Lewis碱之间相对强的配位键在分子识别方面受到的关注较少，也从未用于选择性有机合成。在此背景下，我们开发了几种具有空间位阻苯氧基配体的体积较大的有机铝试剂。这些体积庞大的铝试剂在溶液中是单体的，因此具有很强的刘易斯酸度，可以结合各种含杂原子的底物，如羰基、羧基和酰胺化合物。该络合作用有时具有立体选择性、区域选择性和化学选择性，可发生与AlCl_3、SnCl_4、BF_3和TiCl_4等普通路易斯酸不能发生的选择性有机反应。特别是三（2,6-二苯基苯氧铝（ATPH））在几个反应中获得了前所未有的反应活性和选择性。1. 碳离子与不饱和醛的共轭加成外选择性Diels-Alder反应立体和不对称Claisen重排4.1,6-加入芳香羰基底物。

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.