C-N Bond Formation Reactions via Transition Metal Catalysis

Aminocarbonylation of N-2-propenyl-1, N-3-butenyl-4, and N-4-pentenylureas 8 proceeds smoothly under the Wacker-type conditions (cat. PdCl₂, stoichiometric CuCl₂, 1 atm of carbon monoxide at 0 °C - r.t.) and furnishes 2-imidazolidinone 4-acetic acids 2, tetrahydro-2-pyrimidinone 4-acetic acids 5 and bicyclic dihydrouracils 10, respectively, in good yields. Bicyclic pyrrolidine lactones 15 and piperidine lactones 18 are obtained under the similar conditions, endo-Carbamates 21 display completely different reactivity from exo-carbamates (e.g., 8', R=CO₂Me), through which the chemoselective cyclization of 23 (e.g., R=CO₂Me) either at the endo-carbamate moiety (providing 24, R=CO₂Me) or at the exo-carbamate moiety (providing 25, R=CO₂Me) is achieved only by changing the reaction medium (the former in trimethyl orthoacetate and the latter in methanol). 4-(1-Methoxycarbonylvinyl)-1,3-oxazolidin-2-ones 27 and -tetrahydro-1,3-oxazin-2-ones 29 are obtained in good yields under the similar conditions optimized for endo-carbamates 21. The nitrogen atom of 0-propargyl carbamates 31 add intramolecularly to the triple bond to furnish 4-alkylidene-1,3-oxazolidin-2-ones 32 by the catalysis of CuCl•Et₃N. Similarly, CuCl•Et₃N promotes the aminocyclization of biscarbamate 33 to provide 32 (R²=CH₂OCONHTs), while Pd₂(dba)₃•CHCl₃ selectively promotes the cyclization to furnish 34, the C₂-C₃ double bond of which undergoes a [2+2] cycloaddition with phenylacetylene and methyl acrylate. The enamine double bond reacts with methyl vinyl ketone and acrolein to provide [2+4] addition products. Allene carbamates 38 and 40 undergo cyclization to provide 4-vinyl-1,3-oxazolidin-2-ones 39 and 4-vinyltetrahydro-1,3-oxazin-2-ones 41, respectively, by the catalysis of Ag⁺•Et₃N. The structurally related 43 (R=aryl, sulfonyl) are also obtained with high stereoselectivity by the reaction of cyclic carbamates 42 and isocyanates under the catalysis of Pd(PPh₃)₄. Allylic aminoalcohols derived from carbamates 39, 41, and 43 are utilized as probes to elucidate the electronic effects of the allylic amino and allylic hydroxyl groups on the stereoselective and/or regioselective cyclization reactions: Cope rearrangement (eq 21), endo-trig cyclization (eq 22), and iodoetherification (eq 23). Making contrast to the Ag⁺•Et₃N catalyzed protioaminocyclization of 38 (eq 16), by the catalysis of Pd(PPh₃)₄, 0-2,3-butadienyl carbamates 55' undergo (2,3-butadien-2-yl)aminocyclization to provide 58. PdCl₂, in the presence of an allylating agent (a large excess), promotes the allylaminocyclization of 55 and furnishes trans-56 in good yields and with excellent stereoselectivity.

amination - aminocarbonylation - C-C multiple bonds - urea - carbamate