Group 2 Catalysis for the Atom‐Efficient Synthesis of Imidazolidine and Thiazolidine Derivatives

Abstract

A wide variety of functionalised imidazolidine-2-ones and -thiones, 2-imino-imidazolidines and thiazolidine-2-thiones have been synthesised under very mild reaction conditions by using simple and cost-effective alkaline earth bis(amide) precatalysts, [Ae{N(SiMe3 )2 }2 (THF)2 ] (Ae=Mg, Ca, Sr). The reactions ensue with 100 % atom efficiency as one-pot cascades from simple, commercially available terminal alkyne and heterocumulene reagents. The reactions take place through the initial assembly of propargylamidines, which are utilised in subsequent cyclisation reactions through addition of the isocyanate, isothiocyanate and, in one case, carbon disulfide reagents. This reactivity is deduced to take place through a well-defined sequence of heterocumulene hydroacetylenation and alkyne hydroamidation steps, which are all mediated at the alkaline earth centre. The rate and regioselectivity of the cyclisation reactions are, thus, found to be heavily dependent upon the identity of the catalytic alkaline earth centre employed. Similarly, the selectivity of the reactions was observed to be profoundly affected by stereoelectronic variations in the individual substrates, albeit by a similar Group 2-centred reaction mechanism in all cases studied.

Nucleophilic Magnesium Silanide and Silaamidinate Derivatives

“…The metric data arising from the diimino-iminoamidate ligand of 8 are very similar to those observed in 7 , while examination of the various C–N bonds within the guanidinate ligand indicates that the primary chain of atoms propagating from the non-magnesium-ligated N7 atom is best viewed as a silyl-terminated sequence of alternating singly bonded nitrogen and carbon centers, with each carbon bearing a pendent N - p -tolylimine function. We have previously observed that similar reactions of group 2 amidinate complexes with organic isocyanates, isothiocyanates, and carbon disulfide enable the catalytic construction of imidazolidine and thiazolidine heterocycles. ,, However, the 3-fold insertion of carbodiimide to provide compound 8 is, to the best of our knowledge, unprecedented. Although we have not yet examined this chemistry any further, we suggest that the contrasting outcomes of the reactions to form compounds 7 and 8 are likely consequences of the enhanced nucleophilic character of the N -alkyl silaamidinate anion of 3 in comparison to that of 6 , in conjunction with the superior electrophilicity of the N , N′ - p -tolyl-substituted carbodiimide.…”

Magnesium Catalysis for the Hydroboration of Carbodiimides

“…Scheme2. (1) 1.42731 (6), N(1)ÀC(4) 1.3883 (15), N(1)ÀC(5) 1.4856 (15), N(2)ÀC(4) 1.2645 (15), N(2)ÀC (3) (13) 1.3871 (2)]. Further catalytic studies involved the use of unsymmetrically substituted carbodiimides, undertaken to assess any steric preference associated with additiono ft he Bpin unit ( Table 1, entries 6a nd 7).…”

“…Although the application of heavier Group 2 (Ca, Sr and Ba) derivatives in molecular catalysis has advanced rapidly during the last decade, an even broader palette of reactivity is now provided by their lighter congener, magnesium . The magnesium‐catalysed addition of terminal acetylenes to carbodiimides, for example, allows access to a variety of propargylamidine small molecules, through a catalytic manifold derived from the sequence of E−H protonolysis and heterocumulene insertion steps shown in the Scheme (a). In such cases, entry to the catalytic cycle, the regiochemistry of the final product and the formation of the new C−C bond are dictated by the protic nature of the C−H bonded terminal acetylene substrate.…”

Alkaline earths as main group reagents in molecular catalysis

“…95 While this stoichiometric reactivity could not be extended to a catalytic regime, the in situ formation of propargyl amidines by pre-catalysts 3a-c and interception with RNCO, RNCS and CS 2 substrates has recently enabled the catalytic and atom-efficient one pot assembly of a wide variety of functionalised imidazolidine-2-ones and -thiones, 2-imino-imidazolidines and thiazolidine-2-thiones. 96,97 In an interesting recent advance Harder and co-workers have suggested that the presence of the group 2 centre is unnecessary in the hydroamination of ArNQCQO and RNQCQNR (R = alkyl) by Ph 2 NH. This study did, however, deduce that the presence of a metal cation is crucial in the intramolecular hydroamination of unactivated CQC bonds in H 2 CQCHCH 2 CPh 2 CH 2 NH 2 and, on this basis, implemented a simple hybrid catalyst consisting of a strong organic Schwesinger base and the salt CaI 2 to provide quantitative conversion to the pyrrolidine product at room temperature.…”