The Highlytrans-Selective Darzens Reaction via Ammonium Ylides

Abstract

The Darzens reaction using electron deficient p-substituted benzyltriethylammonium chlorides with aromatic aldehydes afforded 2,3-diaryl epoxides with trans selectivity (>99%) while the corresponding reaction with electron releasing p-substituted benzyltriethylammonium salts gave the epoxides as diastereomeric mixtures. Epoxide formation of p-trifluoromethylbenzylammonium salt, prepared from p-trifluoromethylbenzyl chloride and DABCO, afforded the corresponding 2,3-diaryl epoxide in high yield (>98%).

Identification of the best-suited leaving group for the diastereoselective synthesis of glycidic amides from stabilised ammonium ylides and aldehydes

“…8 Replacing DABCO for quinuclidine (salt 4 ), the yield dropped significantly (32%). This significant decrease in yield is in contrast to recent reports by Aggarwal et al 7c and Kimachi et al 7a describing either similar or only slightly reduced yields in the syntheses of stilbene oxides using DABCO- or quinuclidine-derived benzylic ammonium ylides. Furthermore, using cinchona alkaloid based ylides ( e.g.…”

“…The striking differences in reactivity should mainly be due to the different leaving group abilities of the different amines and less due to different nucleophilicities as all ammonium ylides are supposed to be highly nucleophilic. 7,13 As species with lower basicity are supposed to have a higher leaving group ability 17 it is obvious why quinuclidine (p K a = 11.4) 18a and triethylamine (p K a = 10.7) 18b are not as good leaving groups as DABCO (p K a = 8.9) 18a and trimethylamine (p K a = 9.8). 18b However, this fact alone does not explain why Me 3 N is by far the best leaving group whereas cinchona alkaloids (p K a of quinine = 8.7) 18c do not yield any product at all.…”

“…This is in full accordance with a recent report by Kimachi et al on the syntheses of stilbene oxides using cinchona-derived benzylic ammonium ylides in THF ( t -BuOK as a base). 7b Surprisingly, this group identified brucine as a suitable chiral amine for the syntheses of enantioenriched stilbene oxides. 7b…”

“…11 However, with respect to the syntheses of epoxides or aziridines only a few examples have been reported so far. Whilst the diastereoselective synthesis of aziridines can be accomplished using DABCO-derived stabilised ammonium ylides, 14 the synthesis of epoxides has so far mainly been limited to semi-stabilised benzylic ammonium ylides 7 and cyano-stabilised 5 ammonium ylides. In addition, it was shown that more stabilised ester-derived ammonium ylides do not undergo epoxide formation.…”

Asymmetric syntheses of three-membered heterocycles using chiral amide-based ammonium ylides

“…Indeed, their use in asymmetric epoxidation and aziridination reactions was found to be rather difficult, mainly due to the weaker leaving group ability of the amine group compared to the use of sulfonium ylides. 6 , 7 , 9 …”