[3+3] Annulation of donor–acceptor cyclopropanes with mercaptoacetaldehyde: application to the synthesis of tetrasubstituted thiophenes

Abstract

A conceptually new method for synthesis of tetrasubstituted thiophenes in two steps from trans-2-aroyl-3-aryl-cyclopropane-1,1-dicarboxylates and 1,4-dithiane-2,5-diol has been developed. It involves AlCl3-mediated [3+3] annulation of the cyclopropane-derived 1,3-zwitterionic intermediates with in situ generated mercaptoacetaldehyde, followed by DBU-induced rearrangement of the resulting tetrahydrothiopyranols. The target thiophenes are produced in 55-82% yields.

Synthetic Applications of Aroyl‐ and Nitro‐substituted 2‐Aryl‐Cyclopropane‐1,1‐Dicarboxylates

“…As expected, when cyclopropanes 1 were reacted with 19 in the presence of AlCl 3 (1 equiv.) in DCM at room temperature, chromatographically homogeneous, diastereomeric mixtures of 20 were obtained in good yields (Scheme ) . These mixtures, upon treatment with DBU in DCM, afforded thiophenes 21 in excellent yields.…”

1,4‐Dithiane‐2,5‐diol: An Attractive Platform for the Synthesis of Sulfur‐Containing Functionalized Heterocycles

“…[50] Srinivasan and co-workers described a one-pot method for the synthesis of tetrasubstituted thiophenes 66 from tetrahydrothiopyranols 65, in turn obtained through [3+3] annulation between trans-2aroyl-3-arylcyclopropane-1,1-dicarboxylates 64 and 1 in the presence of stoichiometric amounts of AlCl 3 (Scheme 22). [49,84] Recently, however, Feng's group described highly diastereo-and enantioselective [3+3] annulation between 1 and a number of aromatic substituted cyclopropyl ketones 130 acting as donor/acceptor cyclopropanes in the presence of N,N′-dioxide-Sc III complex as the catalyst, producing the corresponding chiral tetrahydrothiopyranols 131 (Scheme 44) in moderate yields but with excellent ee (up to 99 % ee) and dr values (up to >19:1). [84] The reactions between donor/acceptor cyclopropanes and 1 reported by Zhang's and Sirinivasan's groups produced only racemic tetrahydrothiopyranol structures.…”

Sc(OTf)3‐Catalysed [3+3] Annulation of Cyclopropane 1,1‐Diesters with Mercaptoacetaldehyde: A Facile Strategy for the Synthesis of Tetrahydrothiopyranols

“…IR (KBr): ν = 3507, 2955, 1737, 1512, 1435, 1253 4, 138.0, 133.0, 129.8, 128.9, 128.2, 127.4, 64.0, 59.8, 53.1, 52.8, 39.3, 35 4, 170.4, 137.4, 133.1, 129.7, 128.9, 128.3, 127.4, 73.4, 60.9, 53.1, 52.8, 41.5, 38.4, 32.4 ppm. 13 C NMR (100 MHz, CDCl 3 ): δ = 171. IR (KBr): ν = 3490, 2954, 1491, 1436, 1266, 1054 4 H),4.30 (td,J = 11.2,4.0 Hz,1 H),3.95 (d,J = 11.2 Hz,1 H),4 H),3.78 (s,3 H),3.09 (dd,J = 13.6,11.2 Hz,1 H),2 H),2.50 (dd,J = 14.0,12.4 Hz,1 H) ppm.…”

“…[11] They have been considered as powerful tools for the construction of various carbocycles and heterocycles. [13] Nowadays, catalysis is the primary trend for organic synthesis. Simple derivatization of the products gave some useful compounds.…”