Synthesis of furans and pyrroles via migratory and double migratory cycloisomerization reactions of homopropargylic aldehydes and imines

Abstract

A novel gold-catalyzed divergent sysnthesis of furans and pyrroles employing readily available homopropargylic aldehydes and imines have been developed. The regiochemical outcome of this reaction is dependent on the substituent on the terminal alkyne of substrate. Thus, substrates possessing alkyl and aryl substituent at the alkyne moiety produce 2,3,5-substituted furans and pyrroles via a migratory cycloisomerizaton reaction. Whereas, their silicon analogues are capable to undergo a double migratory process leading to 2,3,4-substituted heterocycles.

Manifestation of the β-Silicon Effect in the Reactions of Unsaturated Systems Involving a 1,2-Silyl Shift

“…Further expansion of this concept to homopropargylic ketones or imines led to reactions involving double rearrangements. 54 When studying gold-catalyzed [(C 6 F 5 ) 3 PAuSbF 6 ] reactions with substrates of type 122 possessing a cyclic substituent at propargylic position, the formation of the fused ring 129 was observed (Scheme 18). 54 It was suggested that this reaction proceeds via an initial activation of the triple bond followed by cyclization to obtain Similarly, dihydrofurans 132 can be obtained by combining alkynylsilanes 130 and the corresponding aldehydes 131 (Scheme 19).…”

“…54 When studying gold-catalyzed [(C 6 F 5 ) 3 PAuSbF 6 ] reactions with substrates of type 122 possessing a cyclic substituent at propargylic position, the formation of the fused ring 129 was observed (Scheme 18). 54 It was suggested that this reaction proceeds via an initial activation of the triple bond followed by cyclization to obtain Similarly, dihydrofurans 132 can be obtained by combining alkynylsilanes 130 and the corresponding aldehydes 131 (Scheme 19). 55 The reaction tolerates a variety of Ar 1 substituents, phenyl and heterocyclic motifs with both electron-withdrawing and -donating effects, affording the desired product in good to excellent yields.…”

Bottom-up Modular Synthesis of Well-Defined Oligo(arylfuran)s

“…It was demonstrated that functional groups such as methoxy, fluoro, nitro and nitrile could be well-tolerated under these reaction conditions, affording the C2-unsubstituted 3-silylfurans 2F-Si′ as sole regioisomer in good yields. It is supposed that the migration might proceed through a β-silyl palatium carbene intermediate, wherein the 1,2-Si migration is kinetically favored over the 1,2-H [50][51][52][53] (See Supplementary Material for the proposed reaction mechanism). To synthesize 2-silyl-bifurans, a stepwise strategy was adopted with TBS-protected enynals as starting material.…”

[1, 2]‐Migration Reactions Catalyzed by Gold Complexes and their Applications in Total Synthesis

“…Recently, Gevorgyan and co‐workers described a synthetic route toward furans and pyrroles via migratory cycloisomerization sequences (Scheme ) . To this end, homopropargylic aldehydes and imines ( 39 ) were converted in the presence of gold(I)‐catalysts, and the corresponding heterocycles 40 and 41 were isolated.…”

“…[38] Recently, Gevorgyan and co-workers described a synthetic route toward furans and pyrroles via migratory cycloisomerization sequences (Scheme 17). [39] To this end, homopropargylic aldehydes and imines (39) were converted in the 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 presence of gold(I)-catalysts, and the corresponding heterocycles 40 and 41 were isolated.…”