Selective Activation of Aromatic Aldehydes Promoted by Dispersion Interactions: Steric and Electronic Factors of a π‐Pocket within Cage‐Shaped Borates for Molecular Recognition

Abstract

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.

Selective recognition between aromatics and aliphatics by cage-shaped borates supported by a machine learning approach

“…9 However, the energy differ- ence in ΔE S between 3a and 3b (ΔΔE S = |ΔE S (3b) − ΔE S (3a)|) was larger in the catalytic system of 1AB (ΔΔE S = 6.6 kcal mol −1 ) than that in 1bB (ΔΔE S = 5.5 kcal mol −1 ). 9 The enhanced stabilization in the inclusion complex 1AB•3b . 2 was attributed to the large dispersion energy.…”

“…This may be because molecular recognition is defined by multiple cooperative non-covalent interactions within the π-pocket. 9 Herein, we propose a new cage-shaped borate catalyst showing improved selectivity for aromatic compounds through the support of machine learning (ML). Recent advances in ML applications to organic synthetic chemistry [13][14][15][16][17] have significantly contributed to the predictions of yields and selectivity, 13,18 sequential searches for optimal reaction conditions, [19][20][21] and reverse structure searches for catalysts, ligands, or transient states, 14,15,[22][23][24] design of asymmetric catalysts, [25][26][27][28][29][30][31][32][33] predictions of site-selectivity for C-H functionalization catalyzed by a pocket-shaped Rh complex, 34 and estimations of the substrate specificity of enzymes.…”

“…This may be because molecular recognition is defined by multiple cooperative non-covalent interactions within the π-pocket. 9…”

Cage‐Shaped Phosphites Having C3‐Symmetric Chiral Environment: Steric Control of Lewis Basicity and Application as Chiral Ligands in Rhodium‐Catalyzed Conjugate Additions

“…[49,50] Our recent studies have demonstrated its effectiveness in controlling the Lewis acidity of a boron [51,52] or aluminum atom. [53] The Lewis acidity of the cage-shaped borate 1B can be tailored by changing the tethered group (XÀ Y), [54,55] the substituents (R), [52] and/or the π-conjugated system (π) [56][57][58][59] (Figure 1A). Furthermore, the cage-shaped borate 2aB exhibits highly chiral recognition and behaves as a chiral Lewis acid catalyst owing to its inherent helicity.…”

Synthesis of Cage‐Shaped Borates Bearing Pyrenylmethyl Groups: Efficient Lewis Acid Catalyst for Photoactivated Glycosylations Driven by Intramolecular Excimer Formation

“…With the development of photoactivated Lewis acids in mind, we focused on a cage-shaped triphenolic ligand, which has established its effectiveness in controlling the Lewis acidity of a boron [38,39] or an aluminum atom. [40] The Lewis acidity of the cage-shaped borate 1B can be tailored by changing the tethered atom and its substituent (XÀ Y), [41] the substituents (R), [42][43][44] and/or the π-conjugated system (π) (Figure 1B). [45,46] We previously reported that benzofuran-based cage-shaped borate 2B exhibited enhanced catalytic activity under black light irradiation.…”