Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

A novel series of β-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC50 = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

(2R)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin- 7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

Recent developments in the stereoselective synthesis of α-aminoacids

The first direct catalytic asymmetric α-amination of aldehydes is described herein. α-Unbranched aldehydes react in this novel proline-catalyzed reaction with dialkyl azodicarboxylates to give α-amino aldehydes in excellent yields and enantioselectivities.

Direct Catalytic Asymmetric α-Amination of Aldehydes

The asymmetric synthesis of .alpha.-amino acids. Electrophilic azidation of chiral imide enolates, a practical approach to the synthesis of (R)- and (S)-.alpha.-azido carboxylic acids

L'«amination» electrophile d'enolates chiraux derives d'acyl-3 oxazolidones par l'azoformiate de di-t-butyle permet la synthese d'α-hydrazino- et α-aminoacides

Roberta L. Dorow

Papers

The asymmetric synthesis of .alpha.-amino acids. Electrophilic azidation of chiral imide enolates, a practical approach to the synthesis of (R)- and (S)-.alpha.-azido carboxylic acids

Stereoselective amination of chiral enolates. A new approach to the asymmetric synthesis of .alpha.-hydrazino and .alpha.-amino acid derivatives

Asymmetric halogenation of chiral imide enolates. A general approach to the synthesis of enantiomerically pure α-amino acids.

Solution and solid-state structure of a phosphorus-stabilized carbanion

Structure and Dynamics of Phosphorus(V)-Stabilized Carbanions: A Comparison of Theoretical, Crystallographic, and Solution Structures