Control of the Dual Reactivity (Iminium-Dienamine) of β-Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with N-Benzoyl C,N-Cyclic Azomethine Imines

Abstract

1,3-Dipolar cycloadditions of C,N-cyclic azomethine imines with α,β-unsaturated aldehydes can be performed with complete control of the regio-, exo-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to β-alkyl α,β-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the β-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2-C3 (via iminium) and the C3-C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds.

Synthesis of Diheteroatomic Five‐Membered Heterocyclic Compounds from α,β‐Unsaturated Aldehydes

“…In the presence of pyrrolidine‐type organocatalysts 6 , the enantioselective [3+2] dipolar cycloaddition reactions of C,N‐cyclic azomethine imines as dipoles with α,β‐unsaturated aldehydes as dipolarophiles could proceed in two different directions. This dual‐reactivity was independently reported by two research groups in 2014 . Du, Wang and co‐workers used β‐arylmethylenals 110 as substrates in the synthesis of new pyrazole derivatives.…”

Catalytic Asymmetric Inverse‐Electron‐Demand 1,3‐Dipolar Cycloaddition of C,N‐Cyclic Azomethine Imines with Azlactones: Access to Chiral Tricyclic Tetrahydroisoquinolines

“…[6][7][8][9][10] In 2010, the group of Maruoka disclosed as eminal asymmetric NED 1,3-DC of C,N-cyclic azomethine imines with a,b-unsaturated aldehydes by involving at itanium/BINOLate complex. [6][7][8][9][10] In 2010, the group of Maruoka disclosed as eminal asymmetric NED 1,3-DC of C,N-cyclic azomethine imines with a,b-unsaturated aldehydes by involving at itanium/BINOLate complex.…”

“…[6a] Shortly after, ac hiral dicarboxylic acid catalyzed asymmetric IED 1,3-DC of azomethine imines with vinyl ethers and vinylogous azaenamines was reported by the same group. [7] Meanwhile,c hiral isothioureas and N-heterocyclic carbenes were also utilized to catalyze such transformations. [7] Meanwhile,c hiral isothioureas and N-heterocyclic carbenes were also utilized to catalyze such transformations.…”

Catalytic Asymmetric Inverse‐Electron‐Demand 1,3‐Dipolar Cycloaddition of C,N‐Cyclic Azomethine Imines with Azlactones: Access to Chiral Tricyclic Tetrahydroisoquinolines

“…Recently,cycloadditions of C,N-cyclic azomethine imines have emerged as one of the most prevailing protocols for the construction of polycyclic THIQs,because such substrates can lead to normal-electron-demand 1,3-dipolar cycloadditions (NED 1,3-DCs) with electron-poor alkenes,a sw ell as inverse-electron-demand 1,3-dipolar cycloadditions (IED 1,3-DCs) with electron-rich alkenes. [6][7][8][9][10] In 2010, the group of Maruoka disclosed as eminal asymmetric NED 1,3-DC of C,N-cyclic azomethine imines with a,b-unsaturated aldehydes by involving at itanium/BINOLate complex. [6a] Shortly after, ac hiral dicarboxylic acid catalyzed asymmetric IED 1,3-DC of azomethine imines with vinyl ethers and vinylogous azaenamines was reported by the same group.…”

“…[6b] Then, Wang et al developed an amine-catalyzed asymmetric 1,3-DC of azomethine imines with aldehydes. [7] Meanwhile,c hiral isothioureas and N-heterocyclic carbenes were also utilized to catalyze such transformations. [8] Very recently,g roups of Shi and Guo independently published the phosphine-catalyzed enantioselective [3+ +2] and [3+ +3] cycloadditions,respectively,ofazomethine imines with d-substituted allenoates and MBH carbonates.…”