Regiodivergent reactions

Reaction of epichlorhydrin a-Acetoxy sulfide Enzymes and metals together Hydrogenation Parallel Kinetic Resolutions Regiodivergent resolutions Double Methods... 

In a somewhat different sequence involving allylic C—O bond cleavage, regiodivergent RRM has been observed in the reaction of dihydrofuran (R,S)-111 with ethylmagnesium chloride and a chiral zirconium catalyst 112 (Scheme 6.24) [44]. The formation of 113 and 114 occurs via carbometaUation of the alkene followed... 

Another example of a regiodivergent qrdiTation of a racemic substrate is shown in Scheme 6.30 [51]. Racemic 140 was treated with Pd in the presence of chiral hgand 141, and the crude reaction mixture was oxidized using Dess-Martin periodinane (DMP) to form the bicychc products 143 (42% ee) and 144 (95% ee). Formation of the initial cydized product 142 is beheved to occur via the hemiacetal resulting from reversible addition of isopentanol to the ketone, followed by internal oxycarbonylation of the alkyne. Lower enantiomeric purity in 144 was observed when less bulky alcohols were used in place of the isopentanol. In contrast, the product 143 does not incorporate the alcohol and htde variation in enantiomeric excess was observed using different alcohols. 

The versatility of this approach was demonstrated by applying it to seven different substrates (Scheme 3.17). The corresponding chiral products were obtained in very good to excellent conversions (63-99%) and absolute stereoselectivities (>99%), particularly when regiodivergent oxygenations were in principle possible. Thereby, the major classes of reactions in asymmetric synthesis or racemate resolution were investigated (desymmetrization, kinetic resolution, and regiodivergent trans formations). 

A ruthenium-catalyzed intramolecular olefin hydrocarbamoylation for the regiodivergent synthesis of indolin-2-ones and 3,4 dihydroquinolin-2-ones was disclosed by Chang and coworkers (Eq. (7.3)) [8]. The reactions underwent smoothly without requiring external CO atmosphere. In the presence of combined catalysts of Ru3(CO)i2/Bu4NI, a 5-exo-type cyclization proceeds favorably to form indolin-2-ones as a major product in good to excellent yields in DMSO/toluene cosolvent (catalytic system A). When the reaction was conducted in the absence of halide additives in NAf-diniethylacetamide (DMA)/PhCl (catalytic system B), 3,4-dihydroquinolin-2-ones were obtained in major in moderate to high yields via a 6-endo cyclization process. An excellent level of regioselectivity was observed with a variety of substrates to deliver 5-exo- or 6-endo-cyclized lactams. 

Scheme 41.41 Regiodivergent reactions through catalytic enantioselective silylation of chiral diols by Snapper, Hoveyda et al.

Jana CK, Studer A. Divergent reactions for racemates catalytic, enantioselectives and regiodivergent nitroso... 

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