Organic Chemistry of Cinchona Alkaloids

Hans Martin Rudolf Hoffmann and Jens Frackenpohl 

During the last two decades, cinchona alkaloids have emerged as powerful chiral auxiliaries leading to well-known landmark developments in asymmetric synthesis already described in preceding chapters but more recently, these alkaloids themselves have been shown to undergo some remarkable transformations and skeletal shifts that are rapidly widening the outlook in the chemistry of cinchona bases. 

Conventional -elimination with deprotonation at C9 Since a hydroxyl proton such as C9 OH is generally more mobile and acidic than the C9—H proton, it is not immediately obvious why the C—H proton should come off at all. 

Deprotonation at C9 with extended conjugation seems feasible because the resulting enol i is sterically stabilized and of a type known to exist transiently [2]. Tautomer i is an activated oxyallyl system [3], which is built into a l,5-N,N-acetal. 

It has been suggested that cinchona bases, although most valuable chiral auxiliaries (e.g., the AD reaction [5] and asymmetric phase-transfer reactions [6]), are very unlikely to find application as (chiral) building blocks [7]. The recent developments outlined herein will change this view. 

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The chemistry of cinchona alkaloids is more than just a collection of exotic organic compounds. It is also about stereochemistry of a privileged class of natural products and, in its widest sense, about ideas, reaction mechanism, supramolecular chemistry, biological and catalytic activity, and beyond. The fascination and challenge of the organic chemistry of cinchona alkaloids need never stop. 

This multiauthor handbook will cover the whole spectrum of cinchona alkaloid chemistry ranging from the fundamentals to industrial applications. This book is organized in four units, namely, the use of cinchona alkaloids as chirality inducers in metal-promoted reactions (Chapters 2-4), the use of cinchona alkaloids as chiral organocatalysts (Chapters 5-11), the organic chemistry of cinchona alkaloids themselves (Chapter 12), and the use of cinchona alkaloids as chiral discriminating agents... 

Hoffmann HMR, Frankenpohl J (2009) Organic chemistry of cinchona alkaloids. In Song ChE (ed) Cinchona alkaloids in synthesis catalysis. Wiley-VCH, Weinheim, p 359... 

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