A One-Pot Assembly of Fully Substituted Alkyl 5-Aminothiophene-2-carboxylates from Allenes, Isothiocyanates, and Alkyl 2-Bromoacetates

Abstract

A novel simple approach to highly functionalized multisubstituted thiophenes such as alkyl 4-alkoxy-5-amino-3-methylthiophene-2-carboxylates through the one-pot sequential reaction of α-lithiated alkoxyallenes with isothiocyanates and alkyl 2-bromoacetates has been discovered. The process proceeds quickly (30-45 min) via in situ formation and intramolecular cyclization of alkyl 2-[(2-alkoxybuta-2,3-dienimidoyl)sulfanyl]acetates (1-aza-1,3,4-trienes).

Cyclizations of The Isothiocyanates‐Derived Azatrienes: The CuBr–Catalyzed Switching from Thiophenes to Pyrroles

“…IR (neat): ν̃ = 2953, 2864, 2835, 1944 (=C=), 1740, 1623, 1545, 1456, 1445, 1436, 1396, 1295, 1268, 1200, 1156, 1091, 1047, 1007, 904, 779, 700, 568 cm –1 . The data are consistent with those previously reported …”

“…C 50.21, H 6.09, N 6.51, S 14.90; found C 50.42, H 5.98, N 6.38, S 14.71. The data are consistent with those previously reported …”

“…Direct synthesis of thiophenes 2a , 2b , 2f , 2g , 2i , 2k , and 2m in good yields is described in work . …”

“…–48 °C) (procedure B) (Table , entries 7, 10, and 16) and a shorter the reaction time (1–2 min) (procedure C) (Table , entries 8, 11, 12, and 17), no or just negligible formation of thiophenes 2 occurs. It was also observed that the addition of a proton donor [ t BuOH (procedure D) (Table , entry 13) or water (procedure E) (Table , entries 18–21, and 23)] to the reaction mixture (before or just after S‐alkylation) even more successfully inhibited the undesirable process of thiophene formation because of the expected deactivation of basic species, which initiated the transformation of 1‐aza‐1,3,4‐trienes 3 into thiophenes 2 …”

“…Recently, we have found that when methyl or ethyl 2‐bromoacetates are used as alkylating agents in the reaction of α‐lithiated alkoxyallenes 1 with isothiocyanates, substituted thiophenes 2 are obtained via intermediate 1‐aza‐1,3,4‐trienes 3 (Scheme ) …”