Gold‐Catalyzed One‐Pot Synthesis of 1,3‐Disubstituted Allenes from Benzaldehydes and Terminal Alkynes

Abstract

A new and facile one-pot synthesis of 1,3-disubstituted allenes, using cheap and readily available terminal alkynes, benzaldehyde derivatives and morpholine, was developed. A small library of 20 allenes demonstrates a broad applicability, with yields up to 86%. Isotopic-labelling and cross-over experiments strongly indicate that our reaction proceeds via a two-step A 3 -coupling followed by a 1,5-hydrogen shift process.

Gold‐Catalyzed One‐Pot A3‐Coupling/1,5‐Hydride Shift/Schmittel‐Type Cyclization: From Aldehydes, Amines and Alkynes to the Synthesis of Benzo[b]fluorenes

“…In analogy to reports on 1,5‐migration of hydrogen on propargylamines and the reports on the in situ allene trappings to benzo[ b ]fluorenes, we propose the reaction mechanism to be initiated by an A 3 ‐coupling reaction to afford the propargylamine 4 , which then can undergo a 1,5‐hydride shift to generate A , and after elimination the allene 5 . Once formed, the allene directly engages in an Au‐catalyzed Schmittel‐type cyclization by first coordinating to gold (as depicted by intermediate B ).…”

“…Additionally, by avoiding the installation of functional groups, this method can lead to the one‐pot formation of three new carbon–carbon bonds and cuts down the number of synthetic steps usually required to access benzo[ b ]fluorenes. Ultimately, by applying our allene synthesis method to this reaction, we also hope to not only demonstrate that this method is interesting for the synthesis of benzo[ b ]fluorenes themselves but also to illustrate how easily allenes can be accessed as intermediates in cascade reactions.…”

“…Recently we reported a one‐pot atom‐ and step‐economic method for the synthesis of benzo[ b ]fluorenes from aldehydes, alkynes and amines, proceeding via an A 3 ‐coupling/formal [4+2] thermal cycloaddition, leading to two different benzo[ b ]fluorene regioisomers as products (Scheme .e). [6i] On the other hand, inspired by gold‐catalyzed 1,5‐hydrogen migrations from propargylamines, we also have reported that allenes can be synthesized from aldehydes, alkynes and morpholine, through propargylamine intermediates . In this context, aiming to integrate our allene synthesis into a cascade reaction, we envisioned that the allene VI could be formed in situ, with no need for the pre‐installation of any reaction trigger, from propargylamine V (Scheme f).…”

Room Temperature Allenation of Terminal Alkynes with Aldehydes

“…(2) In most cases the reaction is not catalytic in metal due to the intrinsic nature of in situ formed water and imine, which must have reduced the catalytic performance of the metal species. Inspired by the very limited protocols at 70 °C by Hashmi [3h] and us, [3g] the gold‐catalyzed 1,5‐H transfer of propargylic amines, [5] and our own understanding of the mechanism for this transformation, herein, we wish to report a room temperature ATA reaction affording allenes in decent yields with a wide scope by identifying a gold(I)‐carbene as the catalyst, 2,2,2‐trifluoroethanol (TFE) or 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) as the solvent and 1‐methyl‐1,2,3,4‐tetrahydroisoquinoline as the amine with the 1,5‐H transfer being mediated by the aldehyde (Scheme 1).…”

Zinc Iodide Catalyzed Synthesis of Trisubstituted Allenes from Terminal Alkynes and Ketones

“…An NHC-coordinated Au catalyst was also shown to be efficient, toward 1,3-disubstituted allenes, under low catalyst loading (2.5 mol %) and mild conditions (70 °C, Scheme 1 ). 27 Minor drawbacks of this catalytic system are the prolonged reaction times (48 h), in addition to its focus on aryl-substituted aldehydes.…”