DOI: 10.1002/adsc.201500044 A Metal-Free Approach Toward Saturated N-Propargyl Hetero- cycles via an Annulation/Decarboxylative Coupling Sequence Huangdi Feng, a Huihui Jia, a and Zhihua Sun a, * a College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 333 Longteng Road, 201620, People’s Republic of China Fax: (+ 86)-21-67791432; phone: (+ 86)-21-67791432; e-mail: sungaris@gmail.com Received: January 19, 2015; Revised: May 8, 2015; Published online: June 26, 2015 Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500044. Abstract: A three-component reaction of a 1,2- amino alcohol or 1,3-amino alcohol with a formalde- hyde solution and a propiolic acid was developed and studied. This new strategy provided an efficient access to biologically and synthetically important N-propargyl oxazolidines, 1,3-oxazinanes and thia- zolidine bearing a diverse range of substituents in good yields. The transformation involves a cascade process that begins with an annulation and is fol- lowed by the metal-free decarboxylative coupling. Keywords: decarboxylative coupling; metal-free; annulations; N-propargyl heterocycles; three-com- ponent reaction Nitrogen-containing heterocycles have received in- tense attention among medicinal chemists as they dis- play a broad spectrum of biological activities. The ox- azolidine moieties serve as valuable pharmacophores for biomedical research, [1] and versatile synthetic in- termediate for the synthesis of heterocycles, [2] amino alcohols, [3] and natural products. [4] Moreover, chiral oxazolidines have been widely utilized as catalysts in asymmetric synthesis. [5] Additionally, benzazolo-oxa- zolidines have been exploited as organic molecular switches with large nonlinear optical contrast. [6] Due to this, substantial progress has been achieved for their synthesis. Some examples are the condensation of 1,2-amino alcohols with aldehydes and ketones. [7] Recently, Yoon and co-workers discovered a new ap- proach to oxazolidines via copper or iron catalyzed oxyamination of alkenes with oxaziridines. [8] Jarvo and Du reported a transition metal catalyzed cycload- dition reactions of butadiene monoxide with imines. [9] Later the Antilla group expanded this chemistry to the use of 2-chloroethanol as a butadiene monoxide replacement. [10] In addition, Wang described a method to access benzoxazoles by an amine-catalyzed annula- tion. [11] Of these methods, the condensation of 1,2- amino alcohols is still the traditional protocol for as- sembly of oxazolidines (Scheme 1a), but examples for the constitution of N-substituted oxazolidines by domino reaction of 1,2-amino alcohols, aldehydes and nucleophiles have been rarely studied or reported. In analogy to oxazolidines and propargylamines, [12] N- propargyl oxazolidines could show various useful bio- activities and provide potential impact in the discov- ery of novel lead compounds. However, there have been rare reports on the constitution of this skele- ton, [13] meanwhile, the reaction process is complicated with low atom economy. Therefore, the development of both atom-economic and efficient approaches to the synthesis of structurally diverse N-propargyl oxa- zolidines is very attractive to researchers. In recent years, transition metal catalyzed decar- boxylative coupling reactions have become an attrac- tive research area owing to widely available starting Scheme 1. Synthesis of oxazolidines from amino alcohols. Adv. Synth. Catal. 2015, 357, 2447 – 2452 # 2015 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 2447 COMMUNICATIONS