Synthesis with perfect atom economy: generation of furan derivatives by 1,3-dipolar cycloaddition of acetylenedicarboxylates at cyclooctynes.

Klaus Banert,Tina Walther,Sandra Bochmann,Oliver Plefka,Marcus Korb,Florian Taubert,Heinrich Lang,Andreas Ihle,Tobias Rüffer

doi:10.3390/molecules190914022

Abstract

Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes to yield polycyclic products 3b–d, orthoesters 4a–c, ketones 5 or epoxides 6a,b, respectively. Treatment of bis(trimethylsilyl) acetylenedicarboxylate (1c) with cyclooctyne leads to the ketone 7 via retro-Brook rearrangement of the dipolar intermediate 2c. In all cases, the products are formed with perfect atom economy.

Highlights

Esters of acetylene dicarboxylic acid and especially dimethyl acetylenedicarboxylate (DMAD, 1a) are highly versatile tools for organic chemists [1,2,3,4,5,6,7]
The resulting carbene intermediate 2a is trapped by a third molecule of 1a, and, Diels-Alder reaction of the furan unit with a fourth molecule of 1a leads to 3a
The 1,3-dipolar cycloaddition of 1a at the ring-strained dipolarophile cyclooctyne to generate the intermediate 2b is much more rapid than the dimerization of 1a to produce 2a. This allows the synthesis of the interception product 3b without heating or long reaction times and formation of several other trapping products of 2b

Summary

Introduction

Esters of acetylene dicarboxylic acid and especially dimethyl acetylenedicarboxylate (DMAD, 1a) are highly versatile tools for organic chemists [1,2,3,4,5,6,7] These compounds are successfully utilized as dienophiles in Diels–Alder reactions, as dipolarophiles in 1,3-dipolar cycloadditions and as components in [2 + 2] or other cycloaddition reactions. The carbene intermediate 2a can be trapped in the presence of electron-poor dimethyl fumarate to generate the cyclopropane-derived compound dihydro-3a, but with an excess of tolane, the corresponding interception product was obtained only in trace amounts.

Results and Discussion

General Information

Conclusions