Cycloaddition Reactions of 1-Lithio-1,3-dienes with Aromatic Nitriles Affording Multiply Substituted Pyridines, Pyrroles, and Linear Butadienylimines

Abstract

Fully or partially substituted 1-iodo- or 1-bromo-1,3-dienes could be readily lithiated using t-BuLi or n-BuLi to afford their corresponding 1-lithio-1,3-diene derivatives in quantitative yields. When these in situ generated lithium reagents were treated with organonitriles, depending on the substitution patterns of the butadienyl skeletons, substituted pyridines, pyrroles, and/or linear butadienyl imines were formed in good to excellent yields via N-lithioketimine intermediates. In the cases of 1,2,3,4-tetrasubstituted and 2,3-disubstituted 1-lithio-1,3-dienes, pyridine derivatives or linear butadienyl imines were generally formed depending on the reaction temperatures. When 1,2,3,4-tetrasubstituted 4-halo-1-lithio-1,3-dienes and 1,2-disubstituted 1-lithio-1,3-dienes were treated with organonitriles, pyrrole derivatives or linear butadienyl imines were obtained. Competition between 5-exo and 6-endo cyclization was found to be responsible for the formation of either pyrroles or pyridines. Selective elimination of RLi from the lithiated cyclic N-containing intermediates was observed. The order of elimination was found to be LiCl > Me3SiLi > LiH.

Highly Efficient Synthesis of Stereodefined Multisubstituted 1,4‐Dicyano‐ and 1‐Cyano‐1,3‐butadienes and Their Reactions with Organolithium Reagents

“…[3,7,8,18,19] As shown in Scheme 5, the pyridine derivative 2 a was obtained in 91 % yield of the isolated product from the organolithium reagent 1 a and PhCN. [7,8] The same addition intermediate, N-lithioketimine 4 a, was assumed to be formed also in the reaction of 1-cyano-1,3-butadiene 7 a with PhLi. However, unfortunately, although the reaction of 7 a with PhLi proceeded smoothly, it afforded the pyridine derivative 2 a in a low yield (Scheme 5).…”

“…The other is the 5-exo addition of the iminolithium species to the C=C bond to form the intermediate 6 followed by elimination of LiCl and hydrogen transfer to afford the final 2H-pyrrole product 3 (Scheme 6, path b). [8] When 4-bromodienenitrile 8 c was treated with nBuLi, 2H-pyrrole 3 a was obtained in 75 % yield of the isolated product through a similar process to that described above. Reactions of multisubstituted 1,4-dicyano-1,3-diene derivatives with organolithium reagents: Although reactions of 1,4-dicyanobutadiene with transition-metal complexes have been investigated in several cases, [20, 11c-d] the reactivity of dienedinitriles with main-group-metal compounds has seldom been explored.…”

“…[5,6] We have recently reported reactions of 1,4-dilithio-and 1-lithio-1,3-butadienes 1 with organonitriles that afford pyridines 2 and/or pyrroles 3 through an unprecedented cycloaddition reaction (Scheme 2). [7,8] In our unusual cycloaddition reaction without a nucleophilic substitution step, N-lithioketimine 4 was proposed to be the key intermediate (Scheme 2). [7,8] To extend the scope of these synthetically useful reactions and to further investigate the reaction mechanisms, we planned to treat 1-cyano-1,3-dienes 7 and 8 and 1,4-dicyano-1,3-dienes 9 with various organolithium reagents (Scheme 3).…”

“…[7,8] In our unusual cycloaddition reaction without a nucleophilic substitution step, N-lithioketimine 4 was proposed to be the key intermediate (Scheme 2). [7,8] To extend the scope of these synthetically useful reactions and to further investigate the reaction mechanisms, we planned to treat 1-cyano-1,3-dienes 7 and 8 and 1,4-dicyano-1,3-dienes 9 with various organolithium reagents (Scheme 3). We expected these reactions to lead to the formation of a Abstract: Stereodefined multisubstituted 1-cyano-and 1,4-dicyano-1,3-butadiene derivatives were obtained in excellent yields of the isolated product from their corresponding monohaloand dihalobutadienes and CuCN.…”

Synthetic Methods for Multiply Substituted Butadiene-Containing Building Blocks

“…32 A 1-lithio-1,3-diene reagent possessing a phenyl substituent at position 4 of the butadienyl skeleton was allowed to react with an aldehyde to yield the corresponding dienol 32e after hydrolysis with satu- The reaction of 1,2-disubstituted 1-lithiobuta-1,3-dienes with organonitriles at -78 °C yielded the linear butadienyl-containing imines 38 after quenching with aqueous NaHCO 3 (Scheme 24). 35 When the temperature was increased, pyrrole derivatives 39 appeared in addition to linear imines 38, e.g. formation of 38a and 39a.…”