Asymmetric 1,2‐Carbamoyl Rearrangement of Lithiated Chiral Oxazolidine Carbamates and Diastereoselective Synthesis of α‐Hydroxy Amides

Abstract

Asymmetric 1,2‐carbamoyl rearrangement of lithiated 2‐alkenyl carbamates has been investigated. Deprotonation of chiral 2‐alkenyl oxazolidine carbamates with sec‐butyllithium in ether at −78 °C followed by warming of the resulting 1‐lithio‐2‐alkenyl derivatives to room temperature resulted in 1,2‐carbamoyl rearrangement to provide α‐hydroxy amides. The rearrangement proceeded with excellent diastereoselectivity and in good to excellent isolated yield of the α‐hydroxy amide derivatives. The substrate scope of the reaction was investigated with a variety of 2‐alkenyl and benzyl oxazolidine carbamates. A stereochemical model is provided to explain the stereochemical outcome associated with the rearrangement. Acid‐catalyzed removal of the chiral oxazolidine afforded α‐hydroxy acid in high optical purity.

From intramolecular cyclization to intermolecular hydrolysis: TMSCF2Br-enabled carbonylation of aldehydes/ketones and amines to α-hydroxyamides

“…2 And more convenient methods via the nucleophilic addition of carbonyl compounds with carbamoyl anions such as carbamoyllithiums, 3 carbamoylsilanes 4 or its equivalent isocyanides 5 for the assembly of α-hydroxyamides have also been well-documented. Even though these established two-component methods have made remarkable progress, 6 they still suffer from multiple-step operations, harsh reaction conditions or limited substrate scope. From a retrosynthetic viewpoint, a three-component method is expected for streamlined access to α-hydroxyamides from abundant carbonyl compounds, suitable carbonyl sources and amines.…”

Passerini Reaction to Access α‐Hydroxy Amides by Facile Decarbonylation/Decarboxylation of Oxalic Acid

“…The selected examples depicted in Figure 1 include human bradykinin B1, [1] vitamin B5, [2] an androgen antagonist, [3] a peptidomimetic inhibitor, [4] and a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor. [5] Some recent synthetic approaches to these compounds include decarbonylative alkylation, [6] asymmetric 1,2-carbamoyl rearrangements, [7] arginine-catalyzed Henry type reaction, [8] hydrosilylation reaction, [9] and aminocarbonylation. [10] These approaches usually involve harsh reaction conditions and the use of more complex starting materials.…”

“…Some recent synthetic approaches to these compounds include decarbonylative alkylation, [6] asymmetric 1,2‐carbamoyl rearrangements, [7] arginine‐catalyzed Henry type reaction, [8] hydrosilylation reaction, [9] and aminocarbonylation [10] . These approaches usually involve harsh reaction conditions and the use of more complex starting materials.…”