Copper‐Catalyzed Oxidative Transformation of Secondary Alcohols to 1,5‐Disubstituted Tetrazoles

Abstract

A mild and convenient oxidative transformation of secondary alcohols to 1,5-disubstituted tetrazoles is uncovered by employing trimethylsilyl azide (TMSN 3 ) as a nitrogen source in the presence of a catalytic amount of copper(II) perchlorate hexaA C H T U N G T R E N N U N G hydrate [CuA C H T U N G T R E N N U N G (ClO 4 ) 2 . 6 H 2 O] (5 mol%) and 2,3-dichloro-5,6-dicyano-para-benzoquinone (DDQ) (1.2 equiv.) as an oxidant. This reaction is performed under ambient conditions and proceeds through C À C bond cleavage.Keywords: alcohols; azides; copper; regioselectivity; tetrazoles Metal-mediated transformations are useful and indispensable strategies for C À C and C À heteroatom bond forming reactions in organic synthesis.[1] In addition, C À N bond forming strategies are not only challenging but have a great impetus as they provide avenues for the synthesis of biologically active and therapeutically useful heterocycles.[2] Among the heterocyles, tetrazole and its derivatives form a vital class of nitrogencontaining molecules [3] due to their well-known biological activities [4] as well as vast applications in pharmaceuticals [5a] and material sciences.[5c] Traditionally, 1,5-disubstituted tetrazoles are prepared by (i) the reaction of nitriles with alkyl or aromatic azides, [6] (ii) the reaction of ketones [7] or oximes [8] with sodium azide or hydrazoic acid and (iii) the reaction of amides [9] with sodium azide in the presence of PCl 5 or triflic anhydride, etc. Gold-catalyzed synthesis of tetrazoles using alkynes has been recently reported by Echavarren and Gaydou.[10] Recently, Jiao and coworkers developed a method to synthesize 1,5-disubstituted tetrazoles using 1,3-diphenylpropene, [11] which requires precursors that are relatively difficult to access and require multistep synthetic sequences. [12] Additionally, this protocol uses a large excess of TMSN 3 (5.5 equiv.), harsh reaction conditions (80 8C), and requires additives and long reaction times.In continuation of our investigations on the utility of azides in C À N bond forming reactions, especially leading to the formation of nitriles, [13] and in the light of Jiaos work, [11] we anticipated that secondary alcohols in the presence of a Cu salt, an excess of trimethylsilyl azide (TMSN 3 ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), may form the corresponding azide in situ and then undergo a rearrangement to form the nitrilium ion, which may be trapped in a [2+3] cycloaddition fashion by the excess azide present in the reaction medium (Scheme 1). Herein, we present our detailed investigation for converting secondary alcohols directly to 1,5-disubstituted tetrazoles in a one-pot fashion under ambient conditions. We began our study by investigating the Cu-catalyzed reaction of (E)-1,3-diphenylprop-2-en-1-ol 1a with TMSN 3 as a nitrogen source and DDQ as an oxidant (Table 1). Preliminary studies were carried out using Cu(I) and Cu(II) salts such as CuCl, CuBr, CuI, These are not the final page numbers! ÞÞ COMMUNICATIONS

Lewis Acid Mediated Tandem Reaction of Propargylic Alcohols to Tetrazoles Involving CO‐ and CC‐Bond Cleavage Reactions and a CN‐Bond Formation

“…These results clearly indicate that a,b-unsaturated ketones and amides are not involved in this novel transformation. On the basis of the above observations and previous reports [8,12] , we propose a plausible mechanism for this tandem transformation (Scheme 4). Initially, dehydration of the propargylic alcohol in the presence of TMSCl and molecular sieves (13X) [18] to generate the desired 1-aryl-5-arylvinyl-tetrazole product.…”

“…In this respect, numerous efforts have been made to prepare 1,5-disubstituted tetrazoles. [2][3][4][5][6][7][8][9] Among various methods that introduce a nitrogen source, using azide-containing compounds, which show a high chemical reactivity towards functionalizing the starting materials by different types of reaction modes, has been proven to be efficient. For example, compounds such as ketones, [2] amides, [3] oximes, [4] imidoyl, [5] imidoylbenzotriazoles, [6] and nitriles [7] could generate 1,5-disubstituted tetrazoles with azidecontaining compounds.…”

“…Moreover, the Jiao and Prabhu groups recently reported the Cu-catalyzed direct transformation of simple hydrocarbon or allylic alcohols in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as oxidant to form 1,5-disubstituted tetrazoles, respectively (Scheme 1 a). [8] In 2013, Echavarren and co-workers developed a gold-catalyzed reaction of alkynes with TMSN 3 for the synthesis of 1,5-disubstituted tetrazoles by CÀC-bond cleavage (Scheme 1 b). [9] Al-though a great number of pioneering methodologies have been established, new practical and efficient approaches to 1,5-disubstituted tetrazoles from readily available starting materials are still extremely attractive and desirable.Propargylic alcohols have served as versatile synthons for the construction of various synthetic intermediates, allenes in particular.…”

Copper‐Catalyzed Direct Transformation of Secondary Allylic and Benzylic Alcohols into Azides and Amides: An Efficient Utility of Azide as a Nitrogen Source

“…On the basis of our work in the formation of nitriles32a and tetrazoles32b from their corresponding alcohols, a tentative mechanism has been proposed in which Cu(ClO 4 ) 2 · 6H 2 O is initially treated with the alcohol and TMSN 3 to generate azide I . In the presence of DDQ, azide I is oxidized to give nitrilium intermediate III , which is trapped by water to furnish the corresponding amide (Scheme ).…”

“…Although this method is attractive, it involves starting materials that are not easy to access and require multistep synthetic sequences 31. Recently, we reported the oxidative conversion of alcohols into their nitriles32a and tetrazoles (Scheme ) 32b. During these investigations, it was observed that the corresponding azides were formed as an intermediate, which underwent further oxidation in the presence of DDQ (2,3‐dichloro‐5,6‐dicyano‐ p ‐benzoquinone) to generate a nitrilium intermediate 32.…”