Preparation of the Maleic Anhydride Nucleus from Dichloro γ-Lactams: Focus on the Role of the N-Substituent in the Functional Rearrangement and in the Hydrolytic Steps

Abstract

The preparation of the 3,4-dialkyl-substituted maleic anhydride nucleus, through the functional rearrangement of dichloro g-lactams, allowed the comparison of various N-substituents in the functional rearrangement step. The 2-pyridyl group proved to be the most appropriate N-substituent for the hydrolysis of the 5-methoxy-1,5-dihydro-2H-pyrrol-2-one intermediate into the 5-hydroxy adduct, and for the hydrolysis of the maleimide nucleus into the maleic anhydride. The oxidation of the 5-hydroxy-1,5-dihydro-2Hpyrrol-2-one into the corresponding maleimide was achieved with manganese(IV) oxide.

Efficient and Green Route to γ‐Lactams by Copper‐Catalysed Reversed Atom Transfer Radical Cyclisation of α‐Polychloro‐N‐allylamides, using a Low Load of Metal (0.5 mol%)

“…The diastereomeric ratio ( cis / trans ) of 1a was practically the same in all solvents, about 60:40. Since the cis isomer has a more interesting reactivity than its trans counterpart, being able to be smoothly dehydrohalogenated, the C‐3Cl and the C‐4H can, in fact, easily achieve the antiperiplanar conformation required for the elimination,19a,d,f,h its modest prevalence makes these transformations globally not very attractive.…”

“…First, the presence of a substituent R (cyclization auxiliary) on the N atom of the starting amide A is essential, since it allows the α‐amide radical intermediate B to adopt the correct conformation for the cyclisation (Scheme a) 19a,22. Second, when the C‐3 stereogenic centre of the lactam D carries a halo function, it becomes configurationally unstable under the reaction conditions, and can be epimerised by the same ATRC catalyst (Scheme b) 19a,b,f,h,q,20i. The best stereochemical results are thus achievable when the thermodynamic control is fully operative, the preferred products being those in which the substituents Cl and CH 2 Cl stay on the same face of the ring.…”

Solvent- and halide-free synthesis of pyridine-2-yl substituted ureas through facile C–H functionalization of pyridine N-oxides

“…It is noteworthy that obtained ureas 4n-s are potentially suitable for further modifications. Thus, the halogen atom in the pyridine ring of 4o and 4p could be substituted with various nucleophiles through S N Ar [69][70][71][72][73][74] or metal-catalyzed reactions, [75][76][77][78][79][80][81][82] whereas the methoxycarbonyl group in 4s could be converted to amides and esters, reduced to alcohols or aldehydes as well as undergo the Barton decarboxylation. 83 Based on the above discussion a plausible mechanism for the formation of the urea is given in Scheme 4.…”

Formation of Five- and Six-Membered Heterocyclic Rings under Radical Cyclization Conditions

“…The copper(I)-mediated ATRC of haloacetamides has been examined with a number of ligands to facilitate these reactions. 73,78 Clark et al CH 2 Cl 2 , 50 °C X = tris(2-pyridylmethyl)amine R 1 = Ts, R 2 = H, R 3 = H 95% R 1 = Ts, R 2 = Me, R 3 = H 100% R 1 = Ts, R 2 = Ph, R 3 = H 99% R 1 = Ts, R 2 = Me, R 3 = Me 99% R 1 = Bn, R 2 = Me, R 3 = Me 14% R 1 = Bn, R 2 = Me, R 3 = Me 13%* * Cu(X)Br 2 as catalyst . In most cases, several byproducts (ca.…”