Divergent Regioselectivity in the Synthesis of Trisubstituted Allylic Alcohols by Nickel- and Ruthenium-Catalyzed Alkyne Hydrohydroxymethylation with Formaldehyde

✍ Scribed by Dr. Cory C. Bausch; Ryan L. Patman; Prof. Bernhard Breit; Prof. Michael J. Krische

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 304 KB
• Volume: 50
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.201101496

✦ Synopsis

Dedicated to Professor Barry M. Trost on the occasion of his 70th birthday.

Trisubstituted allylic alcohols [1,2] are ubiquitous in natural products and are readily converted into diverse chiral building blocks by enantioselective epoxidation, [2a,b] cyclopropanation, [2a,c] hydrogenation, [2a,d] and allylic substitution. [2a,e] Among methods for the regio-and stereoselective synthesis of trisubstituted primary allylic alcohols, alkyne hydrometalation or carbometalation mediated by stoichiometric organometallic reagents has found broad use. [3][4][5][6][7] For example, in seminal studies by Corey et al. (1967), [4c] the regio-and stereoselective hydroalumination of propargyl alcohols was used to construct vinyl iodides, which were converted into trisubstituted allylic alcohols upon exposure to lithium dialkyl cuprates. Similarly, alkyne hydromagnesiation and carbomagnesiation with Grignard reagents delivered trisubstituted allylic alcohols regio-and stereoselectively. [6,7] Although alkyne functionalization through hydrometalation and carbometalation remains at the forefront of research, [3][4][5][6][7] the development of equivalent transformations that avoid stoichiometric metal reagents is clearly desirable. Conversely, whereas related nickel-catalyzed alkyne-carbonyl reductive couplings can be highly regioselective, such processes require terminal reductants that are metallic, pyrophoric, or highly mass intensive (e.g. ZnR 2 , BEt 3 , Scheme 1. Previously developed approaches requiring a stoichiometric amount of a reducing agent, and the approach investigated in the current study without exogenous reductants.