Ignacio López

Reactions of thioamides with metal carboxylates in organic media

Abstract Reactions of thioamides with metal carboxylates in organic solvents are described. These processes enable the selective preparation of nitriles, imides or amides depending on the substitution pattern of the starting material. Mechanistic hypotheses supported by experimental evidences, including the unequivocal synthesis of bis(thioacetanilide)mercury(II) as a key reaction intermediate, are also proposed.

3+2 -cycloadditions of 2-aminothioisomunchnones to alkynes: Synthetic scope and mechanistic insights

Abstract This manuscript describes the regiospecific 1,3-dipolar cycloadditions of 2-aminothioisomunchnones (1–3) with methyl propiolate. The structure of compound 4 has been unequivocally determined by X-ray crystallography. Based on these experimental arguments and a theoretical rationale that supports the regiochemistry observed, a mechanistic pathway is discussed to account for the formation of pyridone or thiophene derivatives. The protocol has also been extended to the cycloadditions of aminothioisomunchnones derived from carbohydrates with dimethyl acetylenedicarboxylate to afford interesting glycosylaminoheterocycles.

Expeditious formation of 1,2,4-triazine derivatives via a thiosomünchnone cycloaddition reaction

A novel type of heterocyclization reaction involving the [3+2] cycloaddition of N,N-dialkylamino-substituted thioisomunchnones with azodicarboxylates gives rise to 1,2,4-triazine derivatives after a selective fragmentation pathway of the transient cycloadducts. The X-ray analysis of 7 accounts for the fate of this particular transformation. An asymmetric version using chiral carbohydrate-based thioisomunchnones has also been disclosed.

Three‐ and Four‐Membered Rings from Cycloadditions of 1,3‐Thiazolium‐4‐olates and Aldehydes

2-Aminothioisomünchnones, a well-known family of masked dipoles, react with aromatic aldehydes in a domino cascade reaction that produces episulfides (thiiranes) or beta-lactams (2-azetidinones). This sequence is initiated by a [3+2] dipolar cycloaddition followed by ring opening of cycloadducts and intramolecular rearrangement to afford these unusual ring contractions. The nature of the reaction products depends on the structural characteristics of the starting dipole and the experimental conditions. Episulfides are obtained selectively as cis isomers with respect to both aryl groups, whereas beta-lactams are produced as cis/trans mixtures. These structural features were determined unequivocally by X-ray crystallographic analysis. The beta-lactams still possessed a flexible acyclic chain containing sulfur, a salient lead modification of the bioactive cyclic penems and cephems. The preferential production of exo transition structures was rationalized with the aid of computational calculations at the B3LYP/6-31G* level.

Synthesis of dihydrothiophenes by an amino-directed thioisomünchnone-alkene cycloaddition reaction

Dihydrothiophenes can easily be obtained by a general protocol involving the reaction of 2-aminothioisomunchnones with electron-deficient alkenes. The overall process can be interpreted as a sequential [3+2] cycloaddition/ring-opening cyclization reaction. The structures of the products could be unequivocally assigned by X-ray diffraction analysis. A theoretical study at a semiempirical level (PM3) with a further single-point refinement of energies at the B3LYP/6-31G(*) level also offers mechanistic insights into the stereochemical outcome.

Reactivity of 2-methyl thioisomunchnone with acid chlorides

This work describes the reactivity of 2-alkyl thioisomunchnones, exemplified here by the 2-methyl derivative, which behaves as nucleophile in the presence of both aliphatic and aromatic acid chlorides to give 2-heteroaryl ketones or 2-heteroaryl-1,3-diketones, respectively. However, 2-alkyl thioisomunchnones exhibit its characteristic 1,3-dipole behavior toward unsaturated systems.

Facile Synthesis of 4,5-Dihydro-1,3,4-Thiadiazoles by 1,3-Dipolar Cycloaddition of Thioisomünchnones

The present paper summarizes a straightforward synthesis of 4,5-dihydro-1,3,4-thiadiazoles by the 1,3-dipolar cycloaddition of thioisomunchnones. These reactions have been carried out in dichloromethane and are essentially complete within 60 min at room temperature. Under such mild conditions the asymmetric version has been explored as well. Unequivocal structure elucidation has been accomplished by means of one- and two-dimensional NMR techniques as well as X-ray structure analysis.

Unexpected formation of β-lactams and penem isosteres from mesoionics: sequential ring-opening–rearrangement of [3 + 2] cycloadducts

A novel and simple method has been developed to obtain penem analogs with biologically interesting functionalities, which combines aromatic aldehydes with thioisomunchnones, a readily available class of mesoionic heterocycles.

Correction. Synthesis of dihydrothiophenes by an amino-directed thioisomünchnone-alkene cycloaddition reaction

The affiliation of one of the authors (M. E. Light) has been erroneously assigned. His current address is: Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom