The Dichotomy of Gold‐catalyzed Interplay between Cyanamides and Ynamides: Controllable Switch from [2+2+2] to [4+2] Cycloaddition

Abstract

The gold‐catalyzed interplay between cyanamides and ynamides demonstrates condition‐dependent mechanistic dichotomy. [2+2+2] Cycloaddition proceeds under kinetically controlled conditions to give 2,4,6‐triaminopyrimidines (19 examples, up to 99%). Under thermodynamically controlled conditions, the reactivity switches from [2+2+2]‐ to [4+2] cycloaddition; the latter [4+2] reaction accomplishes 1,3‐diaminoisoquinolines (19 examples, up to 97%). The advantages of both methods include regioselectivity, mild reaction conditions (even for the thermodynamically controlled [4+2] reaction) and the possibility of introducing a variety of dialkyl, diaryl, and heterocyclic amino substituents into the target pyrimidine and isoquinoline cores. The reactions were conducted on gram scales and the versatility of the obtained products was demonstrated by post‐functionalizations.magnified image

Recent Progress in Metal-Catalyzed [2+2+2] Cycloaddition Reactions

“…Upon using Ph 3 PAuNTf 2 (5 mol%) as a catalyst in chlorobenzene at room temperature, a range of diversely substituted 2,4,6triaminopyrimidines were obtained from ynamides bearing various electron-withdrawing N-sulfonyl substituents, with alkyl or aryl groups as R 1 and R 2 , in 66-99% yield (Scheme 77). 139 Interestingly, the reactivity switched from [2+2+2] cyclotrimerization to [4+2] cycloaddition by replacing the gold catalyst with IPrAuNTf 2 and conducting the reaction at 80 °C. These conditions allowed the formation of 1,3-diaminoisoquinolines instead of the 2,4,6-triaminopyrimidines (not shown).…”

Gold-Catalyzed Nitrene Transfer from Benzofuroxans to N-Allylynamides: Synthesis of 3-Azabicyclo[3.1.0]hexanes

“…While the cyclopropanation of related α-oxo carbenes is known, − NT reactions utilizing α-imino carbenes are quite poorly explored: Hashmi and co-workers reported the only gold-catalyzed cyclopropanation of α-imino carbenes generated from anthranils and sulfilimines functioning as NTRs. Inspired by these works and on the basis of our previous experience in gold catalysis, − we hypothesized that benzofuroxans could also serve as a source of gold α-imino carbenes for intramolecular cyclopropanation (Scheme C). We also addressed N -allylynamides, as the reaction partners, in view of their high reactivity in the catalytic annulations and facile customization of their substitution pattern. − …”

Mono- and Diamination of 4,6-Dichloropyrimidine, 2,6-Dichloropyrazine and 1,3-Dichloroisoquinoline with Adamantane-Containing Amines

“…Fluorescent 1-morpholinoisoquinoline-3-amines were synthesized from 1-bromoisoquinoline-3-amine by heating with excess morpholine [29]. Recently, an original approach has been proposed for diamino derivatives of isoquinoline and pyrimidine, consisting of the catalytic cyclization of cyanamides and ynamides in the presence of gold complexes [30].…”

“…1 H-NMR (CDCl 3 ) δ 1.50-1.84 (m, 26H, Ad, CH 2 (Ad)), 2.13 (s, 6H, Ad), 3.20-3.25 (m, 2H, CH 2 (NH)), 3.39 (q, 2H, 3 J = 5.4 Hz, CH 2 (NH)),3.56 (t, 2H, 3 J = 5.3 Hz, CH 2 (O)), 4.30 (t, 1H, 3 J = 5.4, NH), 4.68 (t, 1H, 3 J = 5.6 Hz, NH), 7.14 (s, 1H, H3), 7.17 (s, 1H, H5).13 C-NMR(CDCl 3 ) δ 27.9 (1C, CH 2 (Ad)),30.4 (3C, Ad), 31.5 (3C, Ad), 31.6 (3C, Ad), 31.8 (1C, C quat ), 36.4 (3C, Ad), 38.2 (1C, CH 2 (NH)), 39.0 (3C, Ad), 41.5 (3C, Ad), 41.8 (1C, CH 2 (NH)), 58.5 (1C, CH 2 (O)), 72.3 (1C, C quat (O)), 117.6 (1C, C3), 118.6 (1C, C5), 153.4 (2C, C2, C6). HRMS (MALDI-TOF): m/z [M + H] + calcd for C 28 H 43 N 4 O: 451.3431; observed: 451.3454.…”