Gold-catalyzed bicyclic annulations of 4-methoxy-1,2-dienyl-5-ynes with isoxazoles to form indolizine derivatives via an Au-π-allene intermediate.

Antony Sekar Kulandai Raj,Mu-Jeng Cheng,Kuo-Chen Tan,Rai-Shung Liu,Liang-Yu Chen

doi:10.1039/c9sc00735k

Antony Sekar Kulandai Raj, Mu-Jeng Cheng + Show 3 more

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https://doi.org/10.1039/c9sc00735k

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Abstract

Gold-catalyzed bicyclic annulations of 4-methoxy-1,2-dienyl-5-ynes with isoxazoles afford indolizine derivatives with a structural rearrangement. The mechanism of these new annulations does not involve α-imino gold carbenes generated from gold π-alkyne intermediates. We postulate alkyne attack on gold π-allenes, yielding vinyl gold carbenes. These newly generated carbenes react with isoxazole derivatives to yield Z-3-imino-2-en-1-als, further enabling sequential cyclizations to deliver indolizine derivatives in two distinct classes.

Highlights

The advent of gold catalysis has greatly promoted the synthetic utility of alkynes
We sought to achieve the synthesis of other azacyclic compounds beyond pyrrole or indole derivatives; generation of intermediates other than aimino gold carbenes is a viable route
We postulate an atypical mechanism for these bicyclic annulations via a 1,4-alkyne migration, activated by a gold p-allene intermediate; the resulting vinyl gold carbene In-3 is trapped by an isoxazole to enable initial sequential cyclizations before delivering indolizine products

Summary

Introduction

The advent of gold catalysis has greatly promoted the synthetic utility of alkynes. Apart from the functionalizations of alkynes with O, N and C based nucleophiles, gold catalysts accelerate the development of new alkyne annulations[1] with p-bond motifs. This work reports goldcatalyzed bicyclic annulations of 4-methoxy-1-allenyl-5-ynes with isoxazoles to form 8- and 7-formylindolizines 3 and 5; the structural rearrangement of products is noted here (eqn (3)). We postulate an atypical mechanism for these bicyclic annulations via a 1,4-alkyne migration, activated by a gold p-allene intermediate; the resulting vinyl gold carbene In-3 is trapped by an isoxazole to enable initial sequential cyclizations before delivering indolizine products.

Results

Conclusion