α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation

Abstract

Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.

Traceless Rhodium‐Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of β‐Aryl Ketones

“…One approach to address this limitation has been to develop methods for the in situ removal, or derivatization of these substituents . Intermolecular hydroacylation methods based on S‐chelating substrates are some of the most general processes reported, with aryl‐, heteroaryl‐, alkenyl‐ and alkyl‐substituted aldehydes all proving to be excellent reaction partners –. To extend the utility of these methods, our laboratory has shown that alkenyl‐ and aryl‐derived S‐chelating aldehydes are useful substrates for a series of tandem catalytic processes that deliver traceless hydroacylation products (Scheme a) .…”

Diverse saturated heterocycles from a hydroacylation/conjugate addition cascade

“…This observation is consistent with a serendipitous nding of a previous study from our laboratory. 22 The successful hydroacylation reactions with alkynol 2a conrmed the feasibility of a tandem hydroacylation/cyclisation protocol. Accordingly, we then set out to construct substituted alkynols, with the aim of achieving a diastereoselective cyclisation.…”

Glycosylation of Stannyl Ceramides Promoted by Modified Montmorillonite­ in Supercritical Carbon Dioxide

“…All other solvents and reagents were purchase from Sigma-Aldrich Co. LLC, and used without further purification. The sphingosine 26 and azidosphingosine 27 were synthesized using literature procedures. All glassware utilized were flame-dried before use.…”