One‐Pot Two‐Step Synthesis of 1‐(Ethoxycarbonyl)indolizines via Pyridinium Ylides

Abstract

Pyridinium salts Py+‐CH2‐EWG (EWG = CO2Et, CONEt2, CN, COMe, COPh) reacted with Michael acceptors Ar‐CH=C(CO2Et)(Acc) (Acc = CO2Et, COMe, SO2Me, CONH2) at ambient temperature in the presence of base to give [3 + 2]‐cycloadducts by stepwise [3 + 2]‐cycloaddition of the intermediate pyridinium ylides. Treatment of the crude reaction mixtures with 1 equiv. of chloranil and atmospheric oxygen in the presence of sodium hydroxide gave 1‐(ethoxycarbonyl)indolizines by dehydrogenation and elimination of the acceptor group (Acc). A good yield of indolizine was also obtained from Py+‐CH2CN and iPr‐CH=C(CO2Et)2, which indicates that this method is not restricted to aromatic Michael acceptors. Structurally related isoquinolinium salts react with Michael acceptors analogously to give pyrrolo[2,1‐a]isoquinolines.

Ethenesulfonyl Fluoride: The Most Perfect Michael Acceptor Ever Found?

“…Moderate yields of the trans-1,2-disubstituted cyclopropanes 4aand 4b [11] accompanied by several not identified side products were obtained by the reactions of the sulfonium ylides 2a and 2b with ESF (1)i nt oluene at room temperature.Under similar conditions,the pyridinium ylides 3b and 3c,generated in situ by deprotonation of the pyridinium salts 3b·HBr/3c·HBr with Et 3 N, yielded pyrrolo[1,2-a]quinoline 5 and indolizine derivative 6 (isolated in 56 %a nd 60 %y ield, respectively) after oxidative workup with chloranil (Scheme 1). [12] Thes tructure of 5 was confirmed by singlecrystal X-ray crystallography of its cocrystals with tetrachlorohydroquinone ( Figure 1). Scheme 2suggests that the quinoline ylide 3b first undergoes as tepwise or concerted 1,3-dipolar cycloaddition with ESF (1)t og ive intermediate A,w hich is converted into enamine B by base-induced elimination of HSO 2 F. Owing to the high nucleophilicity of enamines (N generally in the range of 10-16), [5a,13] B subsequently undergoes fast addition to 1 yielding C,w hich is dehydrogenated by workup with chloranil to give the isolated pyrroloquinoline 5.A st wo equivalents of 1 and the base are consumed in this sequence, satisfactory yields were only achieved when more than two equivalents of 1 and Et 3 Nwere employed.…”

“…Under similar conditions, the pyridinium ylides 3 b and 3 c, generated in situ by deprotonation of the pyridinium salts 3 b·HBr/3 c·HBr with Et 3 N, yielded pyrrolo[1,2-a]quinoline 5 and indolizine derivative 6 (isolated in 56 % and 60 % yield, respectively) after oxidative workup with chloranil (Scheme 1). [12] The structure of 5 was confirmed by singlecrystal X-ray crystallography of its cocrystals with tetrachlorohydroquinone ( Figure 1). [a] The nucleophilicity parameters N and s N (in DMSO) of 2 a-2 c were taken from Ref.…”

Electrophilicities of 1,2‐Disubstituted Ethylenes

“…The cycloaddition of 2e with 1c was achieved by treatment of a mixture of 2e·HBr and 1c in CH 2 Cl 2 with NEt 3 , whereas attempts to perform this reaction under biphasic conditions [CH 2 Cl 2 /NaOH (32 % aq.)] [25] led only to polymerization of 1c. However, biphasic conditions were successfully used for the reactions of 2e·HBr with 1d and 1e to give indolizine 10d after oxidation.…”

Ethensulfonylfluorid: der beste je entdeckte Michael‐Akzeptor?

“…Unter ähnlichen Bedingungen ergaben die Pyridinium‐Ylide 3 b , c (in situ durch Deprotonierung der Pyridinium‐Salze ( 3 b , c )⋅HBr mit NEt 3 hergestellt) nach oxidativer Aufarbeitung mit Chloranil das Pyrrolo[1,2‐ a ]chinolin 5 und das Indolizin‐Derivat 6 (isoliert in 56 % bzw. 60 % Ausbeute; Schema ) . Die Strukturzuordnung von 5 wurde durch Einkristall‐Röntgenstrukturanalyse seiner Mischkristalle mit Tetrachlorhydrochinon gestützt (Abbildung ).…”