Enantioselectivity Henry reactions

Scheme 6.161 Product range for the 163-catalyzed enantioselective Henry reaction of arylaldehydes with nitromethane.

Scheme 6.169 Screening reaction to identify (R,R)-configured guanidine-thiourea 186 as matching catalyst for the anti-diastereoselective and enantioselective Henry reaction of (S)-a-amino aldehydes with nitromethane.

The use of bifunctional thiourea-substituted cinchona alkaloid derivatives has continued to gamer interest, with the Deng laboratory reporting the use of a 6 -thiourea-substituted cinchona derivative for both the Mannich reactions of malo-nates with imines [136] and the Friedel-Crafts reactions of imines with indoles [137]. In both reports, a catalyst loading of 10-20 mol% provided the desired products in almost uniformly high yields and high enantioselectivities. Thiourea-substituted cinchona derivatives have also been used for the enantioselective aza-Henry reactions of aldimines [138] and the enantioselective Henry reactions of nitromethane with aromatic aldehydes [139]. 

The enantioselective Henry reaction by using copper acetate-bis(oxazoline) catalyst is reported by Evans . ... 

Catalytic enantioselective Henry reactions are known, such as the use of a chiral copper catalyst or a zinc catalyst. The Henry reaction of nitro-methane an a chiral aldehyde under high pressure gives the p-nitro alcohol with excellent enantioselectivity. ... 

Later, a dramatic jump in the ee values was achieved by the same research group by introducing the thiourea moiety at the 6 -position of 44 [22]. Using 10 mol% of the quinidine-derived catalyst 46, the highly enantioselective Henry reaction between nitromethane and the aromatic aldehydes (electron-rich, electron-deficient, and... 

In 2006, Deng and coworkers reported that the quinidine and quinine derivatives, 49 and 50, respectively, bearing a free OH group at the 6 -position catalyzed the enantioselective Henry reaction of a-ketoesters with nitromethane [23]. In the... 

Quite recently, Bandini, Umani-Ronchi and coworkers also reported the highly enantioselective Henry reaction of the various trifluoromethyl ketones 54 with nitromethane catalyzed by the C6 -hydroxy quinine derivatives S3 (5 mol%) [24]. Various aliphatic and aromatic ketones were smoothly converted to the desired tertiary carbinols SS in high yields and ee values (up to 99%) without any significant electronic or steric demands (Scheme 8.17). The difluoroketones 56 proved just as useful as substrates (Scheme 8.18). Of note, the parent alkaloid, quinine, as a catalyst did not give rise to any asymmetric induction. 

A benzylic nitro group is hydrogenolyzed in the presence of Pd(OH)2, whereas homogeneous catalysts are ineffective and only low conversion is observed with Pt/C (and with Rh/C hydrogenation to amines occurs). In conjunction with an enantioselective Henry reaction, chiral homobenzyhc alcohols are accessible. 

Kogami, Y., Nakajima, T., Ashizawa, T. ef a/. (2004) Enantioselective Henry reaction catalysed by optically active ketoiminatocobalt complexes. Chemistry Letters, 33, 614-615. 

Scheme 2.47 Enantioselective Henry reactions with the use of chiral potassium(i)-his(chromium(iii)-salen) catalyst hearing an oligo(ethylene glycol) linkage.

Scheme 14.13 Catalytic enantioselective Henry reactions catalysed by CPN and CPD derivatives.

A mild Lewis-acid-catalysed enantioselective Henry reaction has been carried out in water at 0 °C, using copper(II) bromide and a prolinol with a pendant phenol (69) yields and ee up to 99% were obtained. ... 

Chiral cyclopropane amino alcohols complexed to zinc catalyse enantioselective Henry reactions. ... 

Cinchona alkaloid derivatives catalyse nitroaldol reactions with isatins in yields/cc s up to 98/95%. An enantioselective Henry reaction of isatins yields 3-substituted 3-hydroxyoxindoles in high yield, ee, and de ... 

Type of reaction C-C bond formation Reaction conditions -Propanol, room temperature Synthetic strategy Enantioselective Henry reaction Catalyst l-Cu(OAc)2 complex... 

Keywords Aldehydes, nitromethane, chiral diamine ligand (l)-Cu(OAc)2 complex as catalyst, n-propanol, room temperature, enantioselective Henry reaction, nitroalcohols... 

Scheme 10.41 Enantioselective Henry reaction catalyzed by guanidine 42.

In 2007, Ooi and coworkers introduced chiral tetraaminophosphonium salts as a new class of Bronsted acids [166]. Similar to the guanidine/guanidinium case, these tetraaminophosphonium salts act as Bronsted bases in their neutral/ deprotonated (triaminoiminophosphorane) form, while they can also be used as mono-functional Bronsted acids in their protonated, phosphonium form. Phos-phonium salt 67, when neutralized in situ with KO Bu, was shown to be a highly effective catalyst in the enantioselective Henry reaction of nitroalkanes with various aromatic and aliphatic aldehydes (Scheme 10.65). The same strategy was further applied to the catalytic asymmetric Henry reaction of ynals [167] and hydrophosphonylation of ynones (Scheme 10.66) [168]. Brfunctional catalysis using this scaffold were also obtained using the carboxylate salts of tetraaminophosphoniums in the direct Mannich reaction of sulfonyl imines with azlactones (Scheme 10.67) [169]. 

Scheme 10.65 Enantioselective Henry reaction of nitroalkanes with aldehydes.

The enantioselective Henry reaction with ketones is challenging, owing to the attenuated reactivity of the ketone carbonyl group compared to the aldehyde carbonyl moiety and the high tendency of tertiary nitro-aldol adducts to undergo a retro-addition reaction under basic conditions [15], Stereoselective construction of... 

Scheme 29.8 Enantioselective Henry reaction between isatins and nitromethane and targeted products (R)-(+)-dioxibrassinin (20) and (S)-(-)-spirobrassinin (21).

Scheme 29.11 Enantioselective Henry reaction of fluoromethyl ketones catalyzed by 24.

Scheme 27 Synthesis of 5-lactones via enantioselective Henry reaction...

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