Synthesis of bicyclic lactams using novel Schmidt reactions

Abstract

Several γ,δ-unsaturated β-diketones were prepared by acylation of the lithium enolates of cyclic ketones by cinnamoyl chlorides. Reaction of the cinnamoylcyclohexanones with 2 equivalents of hydrazoic acid in sulfuric acid gave bicyclic lactams in good yields. The mechanism of this process involves a Schmidt reaction, followed by addition of HN 3 to the enone, migration of the aryl group onto nitrogen, and a cyclisation in which the arylamino group is displaced by the amide nitrogen. The scope of the reaction is limited to the preparation of 7-5 bicyclic systems from enoyl cyclohexanones, other precursors gave dihydropyrones or complex mixtures.

Preparation of β-Keto Esters and β-Diketones by C-Acylation/Deacetylation of Acetoacetic Esters and Acetonyl Ketones with 1-Acylbenzotriazoles

“…β -Keto esters and β -diketones have been important intermediates in organic synthesis since the discovery of the Claisen condensation more than a century ago. 1a-i Familiar general syntheses of β -diketones and β -keto esters include (i) acylation of ketones or carboxylic esters by acyl halides or esters 2a-d and (ii) acylation of acetylacetone or ethyl acetoacetate and their substituted derivatives by acyl halides or esters followed by base-promoted cleavage of a carbonyl group. 3a-c The above methods offer many useful synthetic procedures, but some acyl halides, such as 3-phenyl-2-propynoyl chloride and 2-pyridoyl chloride, are quite tedious to synthesize, store, and handle and therefore are often prepared in situ. Moreover, β -keto ester and β -diketone anions are ambident; thus, when acetylacetone or ethyl acetoacetate are reacted with electrophiles such as acyl chlorides in the presence of base, both C- and/or O-acylation can occur.…”

Enantioselective Modular Synthesis of Cyclohexenones: Total Syntheses of (+)-Crypto- and (+)-Infectocaryone

“…As acylating agents, activated acyl derivatives were tested that had been used in C-acylation reactions of enolates before: cinnamoyl chloride, cinnamoyl cyanide, N -(cinnamoyl)-imidazole, and N -(cinnamoyl)-benzotriazole (Table ). Enolate formation required close attention, because the enolates of 17 were found to be unstable if deprotonation times exceeding 30 min at −78 °C were employed.…”

γ,δ-Unsaturated β-Diketones by Acylation of Ketones

“…A number of natural products possessing medicinal activity contain γ,δ-unsaturated β-diketones, e.g., siphonarienedione and cycloepiatalantin (Figure ). γ,δ-Unsaturated β-diketones are also very useful intermediates for the synthesis of 4 H -pyran-4-ones, 3-halo-4 H -pyran-4-one pyrazoles, 1-hydroxy-4-pyridones, 3(2 H )-furanones, 4-pyridazinols, 4 H -thiopyran-4-thiones, 5-hydroxy-2-isoxazolines, substituted pyrrolo[1,2- c ][1,2,3]triazoles, and bicyclic lactams 1 Siphonarienedione and cycloepiatalantin.

2 Ketones 1a − f and α,β-unsaturated N -acylbenzotriazoles 2a − e

…”

“…Acylation of ketones to give β-diketones is an important reaction for carbon−carbon bond formation . Diverse methods are used for the synthesis of β-dicarbonyl compounds, and those which provide γ,δ-unsaturated β-diketones from ketones include (i) acylations with α,β-unsaturated acid chlorides in the presence of sodium amide, ,13a pyridine,13b triethylamine,13c or LDA; (ii) reaction with α,β-unsaturated esters in the presence of Si(OMe) 4 /CsF,14a sodium ethoxide, ,,11a or n -butyllithium;14b and (iii) aldol reactions with conjugated aldehydes to give the β-hydroxy compounds, followed by oxidation. , Another carbon acylation (iv) leading to γ,δ-unsaturated β-diketones involves the reaction of ketones with 2,2-diethoxyvinylidenetriphenylphosphorane to give stable ylides, which are treated with benzaldehyde and the resulting enol ethers are cleaved by acid (Scheme ) 1 γ,δ-Unsaturated β-Diketones from Ketones (Literature Methods) …”