Science of Synthesis

DiRocco, D. A.; Rovis, T., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 835.

General Introduction

Aldehydes are important functional groups in synthetic organic chemistry and are used in a variety of bond-forming reactions, typically utilizing the electrophilic character of the carbonyl group. Reactions which reverse this normal mode of reactivity, termed “umpolung”, render the aldehyde nucleophilic, giving rise to acyl anion equivalents and complementary reactivity.[‌1‌] Traditional methods for converting aldehydes into umpolung reagents involve the use of stoichiometric reagents such as dithianes and protected cyanohydrin derivatives.[‌2‌,‌3‌] These methods typically require strong bases and harsh conditions that are incompatible with many functional groups, thereby limiting their utility. The development of catalytic methods for the in situ formation of acyl anion equivalents under mild conditions has been a topic of interest in the past decades. Two related reactions that utilize the umpolung reactivity of aldehydes are the benzoin and Stetter reactions (‌Scheme 1‌).[‌4‌,‌5‌] The key component of both of these transformations is a catalytically generated acyl anion equivalent ‌1‌, capable of forming new carbon—carbon bonds. In the benzoin reaction, the acyl anion equivalent adds to an aldehyde to provide α-hydroxy ketones ‌2‌ as products. Similarly, the conjugate addition of acyl anion equivalent ‌1‌ to a Michael acceptor affords 1,4-functionalized products ‌3‌; this transformation is known as the Stetter reaction.

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Meeeeeee	ee (%)	Meeee (%)	Mee
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	88	88.8	[‌88‌]
	88	88	[‌88‌]
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	88	88	[‌88‌]
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	88	88	[‌88‌]
	88	88	[‌88‌]
	88	88	[‌88‌]
	88	88	[‌88‌]
	88	88	[‌88‌]
	88	88	[‌88‌]

References