Synthesis of 5-(pyrazol-4-yl) pentanoic acids and 4-(pyrazol-4-yl) butanoic acids via a cascade annulation/ring-opening reaction between hydrazone and dienone

TL;DR

A new copper-catalyzed method efficiently produces pyrazolyl pentanoic and butanoic acid derivatives through a cascade reaction.

Contribution

A novel aerobic [3 + 2] annulation/ring-opening cascade reaction using hydrazones and dienones is introduced for synthesizing pyrazolyl acid derivatives.

Findings

A spiro pyrazoline intermediate is formed with unique regiochemistry.

The cascade reaction yields pyrazolyl pentanoic and butanoic acids in good yields.

The method uses a green catalyst and mild conditions with broad substrate scope.

Abstract

Herein, we report an interesting [3 + 2] annulation/ring-opening cascade reaction between hydrazones and exocyclic dienones via an aerobic, copper(ii) catalysis to synthesize 5-(pyrazol-4-yl) pentanoic acid and 4-(pyrazol-4-yl) butanoic acid derivatives. The annulation first affords a spiro pyrazoline with unprecedented regiochemistry, followed by a cascade nucleophilic ring opening by water to yield pyrazolyl pentanoic and butanoic acid derivatives in good yield. Broad substrate scope, inexpensive and green catalyst and oxidant, and relatively mild reaction conditions enhance the versatility of this protocol.

A copper(ii) catalyzed synthesis of 5-(pyrazol-4-yl) pentanoic acid and 4-(pyrazol-4-yl) butanoic acid derivatives via an aerobic [3 + 2] annulation/ring-opening cascade pathway is described.

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