Selective bond formationsa re one of the most importantr eactionsi no rganic synthesis. In the Lewis acid mediated electrophile reactions of carbonyls, the selective formation of ac arbonyl-acid complex plays ac ritical role in determining selectivity,w hich is basedo nt he difference in the coordinativei nteraction between the carbonyl and Lewis acid center. Although this strategyh as attainedp rogress in selective bond formations, the discrimination between similarly sized aromatica nd aliphatic carbonyls that have no functional anchors to strongly interactw ith the metal centers till remains ac hallenging issue. Herein, this work focuses on molecular recognitiond rivenb yd ispersion interactions within some aromatic moieties. ALewis acid catalyst with a p-spacec avity,w hich is referred to as a p-pocket,a st he recognitions ite for aromatic carbonyls is designed. Cage-shaped borates 1Bw ith various p-pockets demonstrateds ignificant chemoselectivity for aromatic aldehydes 3b-f over that of aliphatic 3a in competitive hetero-Diels-Alder reactions. The effectiveness of our catalysts was also evidencedbyintramolecular recognition of the aromatic carbonylw ithin ad icarbonyl substrate. Mechanistic and theoretical studies demonstrated that the selective activation of aromatic substrates was driven by the preorganization step with al arger dispersion interaction, rather than the rate-determining step of the CÀCb ond formation,a nd this was likely to contribute to the preferred activation of aromatic substrates over that of aliphatic ones.

Chiral Lewis acids play an important role in the precise construction of various types of chiral molecules. Here, a cage-shaped borate 2 was designed and synthesized as a chiral Lewis acid that possesses a unique C -symmetric structure composed of three homochiral binaphthyl moieties. The highly symmetrical structure of 2 with homochirality was clearly elucidated by X-ray crystallographic analysis. The peculiar chiral environment of 2⋅THF exhibited chiral recognition of some simple amines and a sulfoxide. Moreover, the application of 2⋅THF to hetero-Diels-Alder reactions as a chiral Lewis-acid catalyst afforded the enantioselective products, which were obtained through an entropy-controlled pathway according to the analysis of the relationship between optical yield and reaction temperature. In particular, the robust chiral reaction field of 2⋅THF allowed the first example of an asymmetric hetero-Diels-Alder reaction with a simple diene despite the requirement of high temperature.

Cage-shaped borates tethered by heavier Group 14 elements (Si or Ge) were synthesized. These possess an intramolecularly transannular p -σ* interaction between the boron center and the tethered Si/Ge atom, which allows the precise tuning of their Lewis acidity. The Lewis acidity was investigated by the ligand-exchange reaction rate and IR measurements with the help of theoretical calculation. The synthesized borates exhibited catalytic activity. This study demonstrated the effectiveness of the direct orbital perturbation of a metal center by space interaction during fine tuning of the Lewis acidity.