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

• Published in: Chemistry : a European journal Vol. 26; no. 65; pp. 15023 - 15034
• Main Authors: Tanaka, Daiki, Tsutsui, Yuya, Konishi, Akihito, Nakaoka, Koichi, Nakajima, Hideto, Baba, Akio, Chiba, Kouji, Yasuda, Makoto
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 20.11.2020; Wiley Subscription Services, Inc
• Subjects: Acids; Aldehydes; Aliphatic compounds; Borates; cage compounds; Cages; Carbonyl compounds; Carbonyls; Catalysts; Chemical bonds; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Dispersion; Lewis acid; Lewis acid catalysts; molecular recognition; noncovalent interactions; Physical Sciences; Recognition; Science & Technology; Selectivity; Substrates; ALDOL; BORON; NUCLEOPHILIC ADDITIONS; borates; COMPLEXES; REACTIVITY; noncovalent interactions; LONDON DISPERSION; LEWIS-ACID CATALYSTS; DIELS-ALDER REACTION; CHEMISTRY; Lewis acid catalysts; molecular recognition; cage compounds; CHEMOSELECTIVITY
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202003594

Selective bond formations are one of the most important reactions in organic synthesis. In the Lewis acid mediated electrophile reactions of carbonyls, the selective formation of a carbonyl–acid complex plays a critical role in determining selectivity, which is based on the difference in the coordinative interaction between the carbonyl and Lewis acid center. Although this strategy has attained progress in selective bond formations, the discrimination between similarly sized aromatic and aliphatic carbonyls that have no functional anchors to strongly interact with the metal center still remains a challenging issue. Herein, this work focuses on molecular recognition driven by dispersion interactions within some aromatic moieties. A Lewis acid catalyst with a π‐space cavity, which is referred to as a π‐pocket, as the recognition site for aromatic carbonyls is designed. Cage‐shaped borates 1B with various π‐pockets demonstrated significant chemoselectivity for aromatic aldehydes 3 b–f over that of aliphatic 3 a in competitive hetero‐Diels–Alder reactions. The effectiveness of our catalysts was also evidenced by intramolecular recognition of the aromatic carbonyl within a dicarbonyl substrate. Mechanistic and theoretical studies demonstrated that the selective activation of aromatic substrates was driven by the preorganization step with a larger dispersion interaction, rather than the rate‐determining step of the C−C bond formation, and this was likely to contribute to the preferred activation of aromatic substrates over that of aliphatic ones. Pick pockets: Cage‐shaped borates with various π‐pockets demonstrate significant chemoselectivity for aromatic aldehydes over that of an aliphatic aldehyde in the competitive hetero‐Diels–Alder reactions. The selective activation of aromatic substrates is driven by the preorganization step, rather than the rate‐determining step of C−C bond formation, in which large dispersion interactions assist the selective recognition of aromatic carbonyl groups over those that are aliphatic.