A New Multicomponent Reaction Catalyzed by a [Lewis Acid]⁺[Co(CO)₄]^- Catalyst:  Stereospecific Synthesis of 1,3-Oxazinane-2,4-diones from Epoxides, Isocyanates, and CO

Abstract

The use of mechanistic information to develop a new, catalytic multicomponent reaction is described. The complex [(salph)Al(THF)2]+[Co(CO)4]- (1, salph = N,N'-o-phenylenebis(3,5-di-tert-butylsalicylideneimine), THF = tetrahydrofuran), which is known to carbonylate epoxides, aziridines, and beta-lactones, was used to catalyze the synthesis of 1,3-oxazinane-2,4-diones from epoxides, isocyanates, and CO. Under optimized conditions, the reaction was both selective and high-yielding. 1,3-Oxazinane-2,4-diones were synthesized from a variety of epoxides and isocyanates, including some epoxides that do not undergo simple ring-expansion carbonylation. The best results were obtained using highly electrophilic isocyanates. The mechanism of the multicomponent reaction was investigated using labeling and stereochemistry, and the data obtained were consistent with the 1-catalyzed formation of beta-lactone and 1,3-oxazinane-2,4-dione from a common intermediate.

Stereoselective Bromofunctionalization of Alkenes

“… Some examples of MCRs such as Strecker synthesis, Hantzsch reaction, Biginelli reaction, Mannich reaction, and Ugi reaction are well documented. In comparison, electrophilic MCRs have been less reported . A likely reason might be due to the common incompatibility of electrophiles with the other components.…”

Ring Expansions of Oxiranes and Oxetanes

“…The more challenging 1,2-disubstituted oxirane substrates required pressurized CO conditions, but still far lower than when aluminum was employed as the Lewis acid. In 2013, Jurczak reported that the Coates catalyst can be generated in situ from the corresponding chloride salt by reacting in the presence of Co 2 (CO) 8. With this method, handling oxygen sensitive Na[Co(CO) 4 ] is avoided, and the reaction also proceeds with MTBE as solvent [3].…”

“…Professor Coates next reported that the intermediate aluminum alkoxide complex could be intercepted with an electrophile prior to the terminating cyclization step (Scheme 3) [4]. By using highly reactive isocyanates as electrophiles, Scheme 1 Carbonylation enabled by an aluminum Lewis acid catalyst 1,3-oxazinane-2,4-diones can be accessed in a single step from oxiranes.…”

“…This was readily achieved using oxiranes derived from homoallylic alcohol precursors in the presence of a catalytic amount of HCo(CO) 4 and without the assistance of a Lewis acid. High carbon monoxide pressure and long reaction times (24 h) are required, as well as gentle heating in DME.…”

Synthesis and Biological Evaluation of Cruentaren A Analogues

“…[40] Other 1,3-oxazinanones are known as well. [41,42,43] Biological testing: The described analogues as well as the diyne 53 were tested for cytotoxicity against the L929 cell line and the inhibitory efficacy on F-ATPase in mitochondrial preparations of bovine heart. The obtained IC 50 values in the cell-culture assay as well as the percentage of F-ATPase inhibition of the compounds at a concentration of 0.1 and 1.0 mm, respectively, are listed in Table 2.…”