Total Synthesis of Natural Terpenoids Enabled by Cobalt Catalysis

Abstract

Transition metal catalysis plays an essential role in the total synthesis of natural products. Cobalt-mediated asymmetric catalysis has successfully been used as a primary or a secondary step in the total synthesis of natural products, especially terpenoids. Terpenoids represent one of the most prominent families among various categories of natural products, attracting immense attention due to their promising physiological activities. This review summarizes the recent advances toward the total synthesis of terpenoids by cobalt-mediated asymmetric catalysis, which may shed some light on their future synthetic efforts toward natural pesticides such as celanguline, azadirachtin, etc.

Diversification of Pharmaceutical Manufacturing Processes: Taking the Plunge into the Non-PGM Catalyst Pool

“…This system has now been widely accepted as a superior process for aerobic epoxidation and hydroperoxysilylation of unactivated alkenes . Most recent, Chen and Xue summarized comprehensively the application of cobalt-catalyzed asymmetric reactions in total synthesis of natural terpenoids …”

“…This route proved to be highly efficient. Moreover, a commercial kg-scale synthetic route for preparation of cinacalcet hydrochloride 120 (Scheme 38B), a calcimimetic agent and calcium-sensing receptor antagonist, was also described by chemists at Ranbaxy taking advantage of Fe(acac) 3 /N-methyl-2-pyrrolidone (NMP) catalyzed Grignard reaction of alkenyl halide 117 and the Grignard reagent meta-(trifluoromethyl)phenylmagnesium bromide (118). 123 The synthetic approach involves C−C bond formation to prepare dehydrocinacalcet (119) followed by a hydrogenation reaction.…”

Recent developments in nickel-catalyzed asymmetric cyclization and cycloaddition of carbonyl-alkynes, cyano-alkynes, and enynes

“…In 2020, Kong and co-workers described a nickel-catalyzed methodology for asymmetric domino cyclization of cyclic 1,3-diketone tethered 1,6-enyne, providing various chiral bridged tricyclo[5.2.1.0 1,5 ]decane skeleton compounds in high yields with excellent enantioselectivities (Scheme 23). 47 A wide scope of mono- or disubstituted phenylboronic acids and (hetero)arylboronic acids were used in this protocol and various substrates with aryl- or alkyl-substituted alkynes also worked quite well in this reaction, smoothly affording the desired products 85a–85h in good yields along with high ee values.…”

“…Transition metal-catalyzed cyclization reactions are powerful tools for the synthesis of cyclic and heterocyclic compounds, which provide an effective strategy for the construction of many novel cyclic molecules and are also widely used in the synthesis of natural products 1 and pharmaceutical molecules. 2 For many years, palladium-catalyzed chemical transformations have dominated the field of transition metal catalysis, and numerous synthetically challenging carbon–carbon or carbon–hetero bonds have been constructed on the basis of palladium catalysis.…”

Diversification of pharmaceutical manufacturing processes: Taking the plunge into the non-PGM catalyst pool

“…105 2.4 IronDespite being significantly cheaper ($144.90 mt) than other first-row transition metals (Ni: $13.845 lb, Cu: $4.2795 lb, Co: $37.195 lb), applications of homogeneous iron catalysts in industry are relatively sparse.…”