Silver-Catalyzed Decarboxylative Azidation of Aliphatic Carboxylic Acids

Abstract

The catalytic decarboxylative nitrogenation of aliphatic carboxylic acids for the synthesis of alkyl azides is reported. A series of tertiary, secondary, and primary organoazides were prepared from easily available aliphatic carboxylic acids by using K2S2O8 as the oxidant and PhSO2N3 as the nitrogen source. The EPR experiment sufficiently proved that an alkyl radical process was generated in the process, and DFT calculations further supported the SET process followed by a stepwise SH2 reaction to afford azide product.

Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids

“…[18c] Under the optimized reaction conditions,ah ost of alkyl amine nucleophiles and electron-poor aryl acetic acids can be decarboxylatively cross-coupled ( Figure 4). Both cyclic and acyclics econdary amines,i na ddition to primary amines, undergo benzylation in moderate to excellent yields (2,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

“…NaN 3 could be used as an easily reducible ammonia surrogate to access primary amines in high yield. [23] Decarboxylative azidation of 56 to form 57 was conducted on gram scale (1 gram of product) in 92 %y ield. Thet arget 57 contains differentiated amino precursor units that were chemoselectively reduced and acylatedtoyield the key amino tetrahydroquinoline pharmacophore.A zide reduction and carbamate installation, acetal deprotection, and one-pot nitro-group reduction/diastereoselective reductive amination afforded the advanced intermediate of DUAL946 (58)in6 1% yield over four steps.…”

“…Included are examples of amines featuring unprotected alcohol groups (11,21,24), various potentially reactive amide or aniline groups (12)(13)(14)16), and electrophilic or potentially oxidizable groups (15,18). When primary amine substrates were used, bis-alkylation was not observed, enabling facile isolation of the alkylated products (22)(23)(24)(25). Marketed aminecontaining drug molecules bearing sensitive functionality, including aryl fluorides and chlorides,f unctionalized N-and S-heterocycles,a nd at etrasubstituted olefin, could be alkylated in good yields (Paroxetine,Debenzyldonepezil, Desloratadine,C rizotinib,F asudil, and Duloxetine; 3, 26-30).…”

Silver-catalyzed remote Csp3-H functionalization of aliphatic alcohols

“…In recent years, the well-designed sulfonyl oxime ether reagents showed great reactivity in alkyl radical chemistry 42 – 46 . Inspired by the recently developed silver-catalyzed radical reactions 47 – 60 and our continues interest in developing radical reactions with sulfonyl reagents 58 , 59 , we envisioned that the sequence silver-catalyzed radical process would achieve the challenging C–H bond functionalization. To investigate our hypothesis, we initially chose A as the radical acceptor for the direct functionalization of the widely existed 1-octanol ( 1a ).…”

Late Stage Azidation of Complex Molecules

“…26,37,38 Recently developed methods include nucleophilic substitution reactions of tertiary alcohols, 39 trapping of the carbon-centered radicals generated through decarboxylation reactions, 40,41 radical functionalizations of olefins, 42−47 and azidation through C–C bond cleavage. 48 In addition to these methods, azides have been prepared by reactions at C–H bonds that are catalyzed by manganese–porphyrin complexes, that are photoinduced or promoted by visible light, or that are conducted with an oxidant such as K 2 S 2 O 8 .…”