Gold‐Catalyzed Synthesis of Tetrazoles from Alkynes by CC Bond Cleavage

Abstract

Cycloadditions of azides with alkynes to form triazoles under thermal conditions (Huisgen cycloaddition) [1] or in the presence of copper [click reaction, copper-catalyzed azidealkyne cycloaddition (CuAAC)] [2,3] are reactions of fundamental importance in organic chemistry. Triazoles can also be obtained by means of ruthenium, [4] silver, [5] and iridium [6] catalysis, as well as by a zinc-mediated process. [7] In sharp contrast, very different reactivity has been observed in the reaction of terminal alkynes with TMSN 3 in the presence of group 11 metal salts and complexes. [8] Thus, the group of Jiao recently made the remarkable observation that alkynes (1; R = alkyl, aryl, alkenyl) react with TMSN 3 in the presence of Ag 2 CO 3 as catalyst to form nitriles (2; Scheme 1). [9] The same group has reported the cleavage of the aryl-alkyne C(sp 2 )À C(sp) bond of alkynes (1) using [Au(PPh 3 )Cl] and AgCO 3 in the presence of H 2 O and trifluoroacetic acid (TFA) to form carboxamides. [10] The formation of nitriles (2) [9] and carboxamides (3) [10] was proposed to proceed by nucleophilic addition of azide to (h 2 -alkyne)metal complexes to form the intermediates 4 a,b, with subsequent protonolysis to give the alkenyl azides 5 (Scheme 2). The nitriles 2 could then be produced by a 1,3-dipolar cycloaddition and subsequent fragmentation of 6. In the presence of TFA, protonation of 5 would form 7, which could evolve by a Schmidt rearrangement [11][12][13] to give the amides 3. A somewhat related cleavage of triple bonds to form nitriles has been reported using TMSN 3 and Niodosuccinimide, and was proposed to proceed via 2-iodo-2H-azirines. [14] We now report that by using the JohnPhos/gold(I) catalyst A, [15] which allows performing reactions in the absence of Ag I , the N-aryltetrazoles 8 are obtained from 1 by C À C bond cleavage with the concomitant insertion of four nitrogen atoms (Scheme 3). In this transformation gold plays a dual role, first activating the alkyne towards nucleophilic attack and then generating the Brønsted acid required for the transformation of the alkenyl azide into the final tetrazole.We first studied the reaction of the aryl alkynes 1 a-c with TMSN 3 [16] and complex A under stoichiometric conditions. Scheme 1. Synthesis of nitriles (2) [9] and carboxamines (3) [10] from alkynes (1) by aryl-alkyne C(sp 2 )ÀC(sp) bond cleavage. DMSO = dimethylsulfoxide, TFA = trifluoroacetic acid, TMS = trimethylsilyl.Scheme 2. Mechanistic proposal for the formation of 2 and 3. [9,10] Scheme 3. Synthesis of N-aryltetrazoles (8) from alkynes (1). DCE = 1,2,-dichloroethane.

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

“…With the wide application of 1,5‐disubstituted tetrazoles in pharmaceutical research, the exploration of efficient synthetic strategies towards these compounds has attracted much attention among synthetic chemists. In this respect, numerous efforts have been made to prepare 1,5‐disubstituted tetrazoles 2–9. 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.…”

“…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 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 CC‐bond cleavage (Scheme b) 9. Although 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.…”

Silver(I)‐Catalyzed Hydroazidation of Ethynyl Carbinols: Synthesis of 2‐Azidoallyl Alcohols

“…(5)]. The reaction of 1 c proceeded well in the presence of 2,2,6, and afforded the vinyl azide product 2 c in 77 % yield, so that a radical process can be excluded for this reaction.…”

“…During our preparation of this manuscript, Echavarren and Gaydou reported another chemoselective reaction of terminal alkynes with trimethylsilyl azide (TMSÀN 3 ) using gold catalysis, affording tetrazoles (Figure 1 b). [6] Inspired by Jiaos pioneering work and by our long-standing interest in developing transition-metal-catalyzed organic reactions, [7] we herein wish to report an unprecedented chemo-and regioselective hydroazidation of ethynyl carbinols. A general and efficient method to access 2-azidoallyl alcohols has thus been developed (Figure 1 c).…”

A Fast, Visible‐Light‐Sensitive Azobenzene for Bioorthogonal Ligation

“…Traditionally, 1,5‐disubstituted tetrazoles are prepared by (i) the reaction of nitriles with alkyl or aromatic azides,6 (ii) the reaction of ketones7 or oximes8 with sodium azide or hydrazoic acid and (iii) the reaction of amides9 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 co‐workers 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.…”