Metal‐Free Azidation of α‐Hydroxy Esters and α‐Hydroxy Ketones Using Azidotrimethylsilane

Abstract

We herein report a commercially available perchloric acid catalyst capable of catalyzing the azidation of a-hydroxy esters, a-hydroxy ketones and taddols using azidotrimethylsilane in dichloromethane at room temperature. Various substituted tertiary alcohols are well tolerated in this reaction. C a -tetrasubstituted a-amino acid derivatives were prepared by one-pot sequential azidation and hydrogenation procedure. The advantage of this newly developed method includes operational simplicity, ready availability of catalyst, scale-up ability, and also good functional group compatibility.Amino acids and their derivatives play an important role in the improvement of life due to their wide applications in medicine, pharmacology, nutrition and so on. [1] In this scenario, non-proteinogenic C a -tetrasubstituted a-amino acids are in particular useful in biochemical researches. [2] Such C a -tetrasubstituted aamino acids represent a type of prominent structural scaffolds widely present in drugs, pharmaceutically and biochemically active compounds (Scheme 1). For example, 2,2-diphenylglycine A [3a] has antibacterial and antifungal properties, and its analogue B [3b] has antagonist activity at group I metabotropic glutamate receptors expressed in CHO cells. In addition, compounds fused with C a -tetrasubstituted a-amino acid motifs also exhibit unique bioactivities and important applications. 4,5-Dihydro-1H-2,4-benzodiazepine C [3c] has antiarrhythmic activity and multi-functionalized compounds D [3d] could serve as effective PTP-1B inhibitors. Therefore, it is very much in demand to develop operationally simple and efficient protocols for the catalytic synthesis of C a -tetrasubstituted aamino acid derivatives.During the past decades, several elegant methods have been developed for the facile synthesis of C atetrasubstituted a-amino acid derivatives, [4] including the Strecker reaction of ketimines, [5] the addition of Scheme 1. Representative bioactive compounds containing C a -tetrasubstituted a-amino acid scaffold.

Facile Direct Coupling Reactions of MOM‐protected Benzylic Alcohols Using Aluminum Chloride

“…In particular, exploitation of azides in the Huisgen reaction or in Click chemistry provides crucial methods for coupling between biomarkers and macromolecules 11 . However, in most synthetic protocols for azido compounds, free alcohols are employed as substrates 12 . Therefore, the scope of the AlCl 3 ‐catalyzed protocol was extended to direct azidation from MOM‐protected alcohols, as illustrated in Table 4.…”

Continuous-Flow Direct Azidation of Alcohols and Peroxides for the Synthesis of Quinoxalinone, Benzooxazinone, and Triazole Derivatives

“…Similarly, Rode accomplished it with the use of a solid povidone and phosphotungstic acid hybrid as a catalyst for heterogeneous azidation of alcohols . More recently, Zhou and Regier achieved it with aqueous perchloric acid and HBF 4 ·OEt 2, respectively (Figure ). Although numerous methods for azidation exist, a more convenient method for the safer generation of azide is highly desired.…”

Manganese(II) Oxidizing Bacteria as Whole-Cell Catalyst for β-Keto Ester Oxidation

“…This reaction provides the most straightforward access to the α-hydroxy-β-dicarbonyl, an intriguing moiety commonly found in various biologically active natural products, agrochemicals, and pharmaceuticals [25][26][27]. Notably, a number of chemical protocols are available to accomplish this oxidation to yield product 2 [28][29][30][31][32][33]. For instance, Lu et al reported a Brønsted acid catalytic method with nitrosobenzene as the oxygen source [28], and Meng and co-workers documented a Zr(IV)/organic peroxide system [30].…”