Arylnitroso compounds 1–3 easily reacted with dimethyl bromomalonate to give the corresponding N‐aryl‐C,C‐dimethoxycarbonylnitrones (4–6). Treatment of C,C‐dimethoxycarbonyl‐N‐( 1‐naphthyl)nitrone (4) with acetylene compounds (dimethyl acetylenedicarboxylate, methyl 2‐butynoate or ethyl phenylpropiolate) caused 1,3‐dipolar cycloaddition to furnish the corresponding 1H‐benz[g]indolines (7a‐c). In a similar manner, the reactions of nitrones 5 and 6 with acetylene compounds afforded the corresponding indolines 9a‐c and 11a‐c together with 4‐oxazolines 13a‐c and 14a‐c.

An external chiral tridentate amino diether ligand 7 catalyzed the condensation reaction of a lithium ester enolate 2 with an imine 3 to give the enantiomerically enriched b-lactam 4 in high yield.

For Abstract see ChemInform Abstract in Full Text.

An asymmetric addition reaction of an ester enolate with a carbonyl compound is one of the important and fundamental carbon-carbon bond forming reactions. [2][3][4] We have been involved in the chiral ligand-mediated asymmetric reactions of highly reactive metalated nucleophiles. [5][6][7][8] Particularly, the reaction of a lithium ester enolate with an imine represents a successful entry to a carbon-carbon bond forming asymmetric reaction, which is mediated by a chiral diether 1 and a chiral aminoether affording the corresponding b-lactam in a satisfactorily high enantioselectivity and high chemical yield.9-13) Straightforward extension of the imine condensation to an aldol-type reaction with an aldehyde as a reaction partner provides a formidable challenge, because the reactivity of an aldehyde itself is high enough to an extent that does not need any activation for the reaction with a lithium enolate (Fig. 1). 14,15) We describe herein that the reaction of a lithium BHA ester enolate with an aldehyde is mediated by a chiral ligand giving a moderate enantioselectivity. 16)Asymmetric Reaction of Propanoate We began our studies with the reaction of tert-butyl propanoate 4 with benzaldehyde 7 (Fig. 2). Treatment of 4 with LDA in the presence of a chiral diether ligand 1 in toluene and then with 7 gave the target 10 as a 27 : 73 mixture of syn-and anti-aldol products (Table 1, Entry 1). However, the enantioselectivity of the acetate 11 was poor. It has been reported by Heathcock that a lithium enolate generated from BHA (2,6-di-tert-buty-4-methoxyphenyl) propanoate 5 in THF reacted with 7 to give stereoselectively anti-aldol product 12.17) Since a BHA ester methodology has been our favourite, 18) we applied the Heathcock procedure in our asymmetric aldol-type reaction in toluene, instead of a THF solvent.Generation of a lithium enolate from BHA ester 5 was possible by butyllithium treatment at Ϫ78°C for 1 h in the presence of 1.3 eq of 1 in toluene, and following treatment with 7 at Ϫ78°C for 5 min to give an almost diastereomerically pure anti-12. The aldol product was immediately subjected to acetylation with acetic anhydride-triethylamine-DMAP in methylene chloride to afford the corresponding acetate anti-13 as a major product of a 7 : 93 mixture (Entry 2). Enantioselectivity of anti-13 was determined to be 32% by a chiral stationary phase HPLC analysis. Improvement of the enantioselectivity was possible by using LDA as a base affording anti-13 in 80% yield and 50% ee (Entry 3). A ternary complex reagent 12) was proved not to be beneficial providing anti-13 in 40% yield and 15% ee (Entry 4). The ether ligand 2 having an ethoxy group was not a choice, giving poorer selectivity of 9% (Entry 5). The best ligand among examined was a tetradentate 3, which mediated the reaction to afford anti-13 in 61% ee. However, the syn/anti selectivity was lost to afford syn-13 as a major product in 35% ee (Entry 6). The present procedure was applicable in the reaction with pivalaldehyde 8 giving the corresponding aldol product a...

An asymmetric addition reaction of an ester enolate with a carbonyl compound is one of the important and fundamental carbon-carbon bond forming reactions. 2-4) We have been involved in the chiral ligand-mediated asymmetric reactions of highly reactive metalated nucleophiles. 5-8) Particularly, the reaction of a lithium ester enolate with an imine represents a successful entry to a carbon-carbon bond forming asymmet-ric reaction, which is mediated by a chiral diether 1 and a chiral aminoether affording the corresponding b-lactam in a satisfactorily high enantioselectivity and high chemical yield. 9-13) Straightforward extension of the imine condensation to an aldol-type reaction with an aldehyde as a reaction partner provides a formidable challenge, because the reactivity of an aldehyde itself is high enough to an extent that does not need any activation for the reaction with a lithium enolate (Fig. 1). 14,15) We describe herein that the reaction of a lithium BHA ester enolate with an aldehyde is mediated by a chiral ligand giving a moderate enantioselectivity. 16) Asymmetric Reaction of Propanoate We began our studies with the reaction of tert-butyl propanoate 4 with ben-zaldehyde 7 (Fig. 2). Treatment of 4 with LDA in the presence of a chiral diether ligand 1 in toluene and then with 7 gave the target 10 as a 27 : 73 mixture of syn-and anti-aldol products (Table 1, Entry 1). However, the enantioselectivity of the acetate 11 was poor. It has been reported by Heathcock that a lithium enolate generated from BHA (2,6-di-tert-buty-4-methoxyphenyl) propanoate 5 in THF reacted with 7 to give stereoselectively anti-aldol product 12. 17) Since a BHA ester methodology has been our favourite, 18) we applied the Heathcock procedure in our asymmetric aldol-type reaction in toluene, instead of a THF solvent. Generation of a lithium enolate from BHA ester 5 was possible by butyllithium treatment at 78 °C for 1 h in the presence of 1.3 eq of 1 in toluene, and following treatment with 7 at 78 °C for 5 min to give an almost diastereomeri-cally pure anti-12. The aldol product was immediately subjected to acetylation with acetic anhydride-triethylamine-DMAP in methylene chloride to afford the corresponding acetate anti-13 as a major product of a 7 : 93 mixture (Entry 2). Enantioselectivity of anti-13 was determined to be 32% by a chiral stationary phase HPLC analysis. Improvement of the enantioselectivity was possible by using LDA as a base affording anti-13 in 80% yield and 50% ee (Entry 3). A ternary complex reagent 12) was proved not to be beneficial providing anti-13 in 40% yield and 15% ee (Entry 4). The ether ligand 2 having an ethoxy group was not a choice, giving poorer selectivity of 9% (Entry 5). The best ligand among examined was a tetradentate 3, which mediated the reaction to afford anti-13 in 61% ee. However, the syn/anti selectivity was lost to afford syn-13 as a major product in 35% ee (Entry 6). The present procedure was applicable in the reaction with pivalaldehyde 8 giving the corresponding aldol product anti-15...