Synthesis of Functionalized Tetrahydropyridines by SnCl₄‐Mediated [4+2] Cycloaddition between Donor–Acceptor Cyclobutanes and Nitriles

Abstract

Cycloadditions of strained carbocycles promoted by Lewis acids are powerful methods to construct heterocyclic frameworks. In fact, the formal [3+2] cycloadditions of donor-acceptor (DA) cyclopropanes with nitriles has seen particular success in synthesis. In this work, we report on the first [4+2] cycloaddition of nitriles with DA cyclobutanes via Lewis acid activation. Tetrahydropyridine derivatives were obtained in up to 91% yield from various aryl activated cyclobutane diesters and aliphatic or aromatic nitriles.

Chiral 3-Acylglutaric Acid Derivatives from Strain-Induced Nucleophilic Retro-Claisen Ring-Opening Reactions

“…The use of strain energy to propel chemical reactions is a well-recognized strategy in chemistry and biology. , The ring-opening reactions of epoxides and aziridines are notable for their diverse uses and applications, and donor–acceptor cyclopropanes are employed for three-carbon homologation, including cycloaddition and ring-opening reactions . By contrast, ring-opening reactions of the cyclobutane ring, whose strain energy (26.3 kcal/mol) is similar to that of cyclopropane (27.5 kcal/mol), would complement those of donor–acceptor cyclopropanes, but they have received far less attention . Ring strain and C–C bond polarization by adjacent substituents provide zwitterionic character to these compounds, allowing them to undergo ring-opening cycloaddition and related transformations (Scheme a) .…”

Diastereoselective synthesis of tetrahydrobenzo[b]azocines by Lu(OTf)3-catalyzed [4+4] cycloaddition of donor–acceptor cyclobutanes with anthranils

“…For instance, the Saigo group reported their pioneering work of [4+2] cycloaddition reactions of aminocyclobutanes with aldehydes and ketones to access lactols in 1991. 4 After that, the formal [4+2] and [4+3] cycloaddition reactions of D–A cyclobutanes with various dipolarophiles such as aldehydes, 5 imines, 6 nitrones, 7 indoles, 8 nitrosoarenes, 9 nitriles, 10 alkenes, 11 1,3,5-triazinanes 12 and diazanes 13 emerged and attracted much attention (Scheme 1a). However, compared with the fact that [4+2] and [4+3] cycloadditions of D–A cyclobutanes have been explored for the synthesis of six- and seven-membered skeletons, 4–14 less attention has been devoted to [4+4] cycloaddition reactions.…”

Synthesis of Hexahydropyridazines by [4 + 2] Cycloaddition of Donor–Acceptor Cyclobutanes and cis-Diazenes

“…Exploiting the ring strain of cyclopropanes and cyclobutanes to generate transient dipoles has proven to be an efficient synthetic strategy. The cycloadditions of donor–acceptor cyclobutane (DACB) were investigated in earnest only after 2009, much later than the success of donor–acceptor (DA) cyclopropanes, when both Johnson and Christie and coworkers reported on aryl-activated DACB cycloadditions with aldehyde dipolarophiles. , The following year, we reported cycloadditions of alkoxy-activated DACBs with imines and aldehydes…”