Synthesis of new N-phosphorylated vinylhydropyridines

Abstract

It is known that secondary phosphine halides react with electron-deficient acetylenes in the presence of bases [1][2][3][4], radical initiators [1,5, 6], metal complex catalysts [7,8], under microwave irradiation [9], and (rarely) in bulk without any catalyst [10] to form tertiary alkenylphosphine halides and the products of bis-addition.In this work, we performed a three-component reaction of diphenylphosphine sulfide Ia and bis(2-phenylethyl)phosphine selenide Ib with acetylenecarboxylates IIa, IIb and pyridines IIIa, IIIb. The reaction occurred under mild conditions (20-52°C, 1-5 h, MeCN) and led to the regio-and stereoselective formation of (E)-N-ethenyl-1,4-dihydropyridines IVa and IVb with yield of 47 and 17%, respectively. In addition, compounds Va and Vb were obtained (up to 63%) as a result of nucleophilic addition of PHcompounds at the triple bond of alkynes II (Scheme 1).Furthermore, formation of the bis-adduct Ph 2 P(=S) CH 2 CH(CO 2 Me)(S=P)Ph 2 IVa was detected in the reaction of phosphine Ia with propiolate IIa in the presence of 2-methylpyridine IIIa.Probably, the reaction pathway included nucleophilic addition of pyridine at the triple bond of electrophilic acetylene, leading to zwitter ion A with carbanionic site trans-positioned with respect to the nitrogen atom. Zwitterion A was in equilibrium with the zwitterion C (carbanionic center is cis position R 1 = Ph (Ia, IVa, Va), R 2 = H, R 3 = Me (IIa, IVa, Va), R 4 = Me (IIIa, IVa), X = S (Ia, IVa, Va); R 1 = PhCH 2 CH 2 (Ib, IVb, Vb), R 2 = EtO 2 C, R 3 = Et (IIb, IVb, Vb), R 4 = H (IIIb, IVb), X = Se (Ib, IVb, Vb). O OR 3 N R 4 R 2 + 20 _ 52 о C, 1 _ 5 h MeCN Ia, Ib IIa, IIb + R 1 2 P X H N R 1 2 P X R 4 H IIIa, IIIb R 2 H R 1 2 P X C + Scheme 1.

Electron-Deficient Acetylenes as Three-Modal Adjuvants in SNH Reaction of Pyridinoids with Phosphorus Nucleophiles

“…On the example of diethyl acetylenedicarboxylate 21a, pyridine 1a and bis(2-phenylethyl) phosphine selenide 2i, it was shown that internal acetylenes of such a type were less effective in the three-component reaction with pyridines and secondary phosphine chalcogenides [49]. Therefore, at an equimolar ratio of these reagents (room temperature, 1 h) E-isomer of N-ethenyl-1,4-dihydropyridine 22 was formed in a 17% yield (Scheme 16).…”

“…A short time ago [37][38][39][40], the nucleophilic substitution of hydrogen (S N H reaction) in non-activated pyridines and their fused derivatives by secondary phosphine chalcogenides (synthesized from red phosphorus [41][42][43][44]) in the presence of electron-deficient terminal and internal acetylenes was disclosed. These reactions involve the step of N-vinylation/ C-phosphorylation of pyridinoids, and are often retained at this step [45][46][47][48][49]. Afterwards, a series of this finding's follow-up works appeared.…”