Unexpected regio- and chemoselectivity of cationic gold-catalyzed cycloisomerizations of propargylureas: access to tetrasubstituted 3,4-dihydropyrimidin-2(1H)-ones

Abstract

Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.

Activation of Primary Amines by Copper(I)-Based Lewis Acid Promoters in the Solventless Synthesis of Secondary Propargylamines

“…At the same time, propargylamines are direct precursors of propargylureas that can undergo silver-or gold-catalyzed cycloisomerization to produce a series of other nitrogen-containing heterocyclic compounds. [11][12][13][14][15] Furthermore, the synthesis of oxazolidinones [16][17][18][19][20][21][22][23] and oxazolones 24 through carboxylative cyclization of propargylic amines with CO 2 is a clean and atomeconomic reaction for CO 2 fixation in the field of green chemistry.…”

Synthesis of a Small Library of Imidazolidin-2-ones using Gold Catalysis on Solid Phase

“…According with the literature, when terminal propargylureas derived from phenyl isocyanates are subjected to gold-catalyzed cycloisomerization in solution the conversion proceeds via a 5-exo-dig N-cyclization mechanism (Figure 1). 48 However, in coincidence with the literature, the internal alkynes combined with the phenyl urea functionalities 7j and 7k led to 6-membered heterocycles 17 through N-6-endo-dig mechanism, followed by spontaneous tautomerization towards the corresponding zwitterion species 16j and 16k (Scheme 5). Compounds 16j and 16k were obtained with moderate to good overall yields 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 15 (Entries 10 and 11) The use of extended alkynes 7d and 7i (m=2) proceeded via 6-exo-dig cyclization with both urea derivatives providing 6-membered heterocycles.…”

AuBr3‐Catalyzed Chemoselective Annulation of Isocyanates with 2H‐Azirine

“…Upon addition of molecular sieves the yield rose to 55 %( entry 8), while in the case of HAuBr 4 ·x H 2 O even 63 %w ere obtained (entry 9). Other Lewis acids, such as Y-,R h-, Pd-, In-, Pt-based Lewis acid, insteado f[ Au],s howed almostn ot ransfer (entry [10][11][12][13][14][15][16]. Though HAuBr 4 ·x H 2 Ow as more effective, AuBr 3 was preferred due to the easier handling of the catalyst (solubility,l ess hygroscopic;entry 17).…”

“…[11b, 13, 14] However, so far no gold-catalyzed direct isocyanate activationsare reported. [15] One importantf eature of gold catalysts is their p-acidity, which enables activation of CÀCm ultiple bonds, such as al-kynes,a lkenesa nd allenes. [16] While we have been workingo n allene chemistry for almostt wo decades, [17] isocyanates, which like allenes contain ac umulene substructure,w ere not investigated so far.…”