Catalytic Z-selective olefin cross-metathesis for natural product synthesis

Abstract

Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000.

Stereoretentive Olefin Metathesis: An Avenue to Kinetic Selectivity

“…[84,85] Since, many breakthroughs in olefin metathesis have been made using molybdenum catalysts. Recent advancements have built on the catalytic structure of Z-selective systems [16][17][18][19][20][21][22] and have provided access to valuable products through stereoretentive olefin metathesis.…”

“…The first examples of kinetically Z-selective processes were reported by Schrock, Hoveyda, and coworkers, identifying both molybdenum-and tungsten-based systems to perform this transformation, which generated the desired Zolefins in high selectivity. [16][17][18][19][20][21][22][23][24][25][26] A large aryloxy-moiety shields one side of the catalyst, forcing the substituents on the generated metallacyclobutane to be all syn (Figure 1 (a)). Later, Grubbs and coworkers introduced a highly efficient, Z-selective olefin metathesis catalyst that utilized a cyclometalated rutheniumcarbene species.…”

Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

“…After the disclosure of the structure 1 by Kirin Brewery, 4) many reports on the synthesis of 1 were published from 1995 to 2011, [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] including practical synthesis of it by Kirin group. 25) As shown in Fig.…”

“…Hence the synthesis of 1 includes two key steps: -selective (or -specific) galactosylation, and the construction of three continuous asymmetric centers of the phytosphingosine chain. To connect a galactose part in -orientation, researchers have used 1-OH free garactopyranose (D), 30,33,44) thiogalactoside (E), 28,30,36,37,41) galactosyl trichloroacetimidate (F), [27][28][29][32][33][34]36,39,43) phosphite (G), 33) phosphate (H), 42) acetate (I), 37) or halide (J) as the galactose donor. 4,25,26,29,31,35,38,40) Hague, 31) and trichloroacetimidate (L) with trimethylsilyl triflate (60%) reported by Kimura et al, 32) gave the highest -stereoselectivity (exclusivity).…”

Title Pages

“…Several new ruthenium N-heterocyclic carbene complexes have been fashioned for specific aspects of olefin metathesis, the most notable being another offering of Grubbs, based on 1-adamantyl-3-mesitylimidazolidin-2-ylidene as ligand, specifically designed for efficient synthesis of challenging (Z)-olefins 25 and considered an improvement/alternative to recently reported molybdenum complexes for the same purpose 26 . An efficient cross-metathesis and ring-closing metathesis of ethyleneammonium salts (including primary amine salts) is also reported 27 , reaction with ethyleneamines generally being unsuccessful.…”