Antonio García Martínez

A new procedure for formylation of less active aromatics

The formylation of aromatic compounds with trifluoromethanesulphonic anhydride/dimethylformamide complex 2 takes place easily as compared to the normal Vilsmeier–Haack reaction.

Bridgehead-norbornane-derived β-amino alcohol catalysts: structural factors influencing the chirality transfer

Abstract Five new optically active bridgehead-norbornane-derived β-amino alcohols with different substitution patterns have been obtained using a straightforward procedure from commercial (+)-camphor or (−)-fenchone, and tested as chiral catalysts in the enantioselective diethylzinc-addition to benzaldehyde. The obtained results show that chirality transfer is mainly governed by the hydroxyl group and, therefore, by the surroundings of the CO stereocenter. On the other hand, the N- alkyl substitution play an important role by modulating the degree of enantioselectivity.

Synthesis of enantiopure norbornane derivatives. Effect of bridgehead substituent on the π-facial selectivity of the reduction of 2-norbornanones and their oximes

Abstract One of the most important features of the synthesis of camphor-derived compounds is the control of the stereochemistry at the C2 position. According to this, reduction of bridgehead-substituted 2-norbornanones 1 and 2-norbornanoximes 3 has been considered by us as a very convenient method for the preparation of different classes of enantiomerically pure 1,2- and 1,3-difunctionalised norbornane derivatives. Factors controlling the stereoselectivity in these reductions, as well as the role played by the nature of the bridgehead functional groups are discussed.

Synthesis, cytostatic and trichomonacide activities of 3,5-bis-(halomethyl)pyrazoles

Abstract Reduction of 1-methyl- and 1-benzyl-diethylpyrazole-3,5-dicarboxylates 2a and 2b with diisobutylaluminium hydride in toluene gave 3,5-bis-(hydroxymethyl)pyrazoles 4a and 4b in very good yields. Alternatively, 4a was obtained by reduction of S,S -diethyl 1-methylpyrazole-3,5-dicarbothioate 3″ with lithium aluminium hydride in lower yield. Treatment of above diols 4a and 4b with thionyl chloride or phosphorous tribromide in dimethoxyethane gave stable 3,5-bis-(chloromethyl)- and 3,5-bis-(bromomethyl)pyrazoles 5a, 6a and 6b . All the compounds synthesized were evaluated as being cytostatic in in vitro cultures of HeLa cells and both 1-methyl- and 1-benzyl-3,5-bis-(bromomethyl)pyrazoles 6a and 6b were found to be powerful cytostatic agents. In biological tests against Trichomonas vaginalis, Entamoeba invadens and Candida albicans , 6a and 6b showed significant trichomonacide activities.

Synthesis and catalytic activity of 10-(aminomethyl)isoborneol-based catalysts : the role of the c(2)-group on the asymmetric induction

Abstract Five enantiopure C(2)-substituted 10-[(dimethylamino)methyl]isoborneols has been prepared by a novel straightforward camphor-based route, and probed as δ-amino-alcohol ligands for the enantioselective addition of diethylzinc to benzaldehyde. The established route constitutes a divergent model procedure for this class of δ-amino-isoborneol ligands, allowing different substitutions, not only at the nitrogen atom, but also at the more interesting hydroxyl-bearing C(2)–norbornane position. This last synthetic possibility has made possible a study of the role played by the group located at the C(2)–norbornane position on the catalytic activity. New catalyst models and transition-state models for explaining such a role are also proposed and discussed.

From natural camphor to (1R,2S)-2-chloromethyl-3-oxocyclopentanecarboxylic acid: a stereocontrolled approach to enantiopure sarkomycin

The preparation of enantiopure (1R,2S)-2-chloromethyl-3-oxocyclopentanecarboxylic acid 9, an interesting possible precursor of the antitumor agent sarkomycin, from a camphor-derived 3-hydroxymethylnorbornan-2-one is reported. The described procedure constitutes the first stereocontrolled approach to sarkomycin starting from commercially available natural camphor. The procedure takes place in only six steps with a high overall yield (59%). The key-step of the described procedure is the stereocontrolled ring opening of a conveniently functionalized 3-oxonorborn-1-yl triflate under a straightforward basic hydrolysis. The described route constitutes a model procedure for the preparation of other enantiopure C2-substituted 3-oxocyclopentanecarboxylic acids; which are related with the sarkomycin family of antitumor agents.

New procedures for the synthesis of heterocyclic substituted and 2,4-difunctionalized pyrimidines

Abstract N -Tosyl-2- and -3-acetylpyrrols 1 or N -tosyl-2-pyrrolidone 5 were condensed with cyano compounds in the presence of triflic anhydride (Tf 2 O) to yield heteroarylpyrimidines. 2,4-Difunctionalized pyrimidines were obtained by reaction of the corresponding 2,4-bis(methylsulfonyl)pyrimidines with nucleophiles.

The role of the substitution pattern on the catalytic activity of chiral bridgehead norbornane-derived β-amino alcohols

The enantioselective addition of diethylzinc to benzaldehyde has been used as standard procedure to test a series of new chiral catalysts derived from norbornane framework. The new ligands are β-amino alcohols possessing both heteroatomic substituents attached to the C(1) and C(2)-endo positions (novel non-coplanar disposition) of a 3,3-dimethylsubstituted norbornane. The results obtained, compared with other previously reported on the related C(2)-exo-7,7-dimethyl series, demonstrate that the relative disposition of the amino, hydroxy and gem-dimethyl groups, as well as the N-alkyl substituents, play an important role on the catalytic activity. Interesting transition-state models have been also proposed in order to explain the observed experimental results.

Influence of highly preorganised 7,7-diphenylnorbornane in the free energy of edge-to-face aromatic interactions.

The influence of preorganised 7,7-diphenylnorbornane in the stability (Ka) of host-guest complexes as well as in the determination of the energy of edge-to-face aromatic interactions has been investigated. The guest molecules studied bind more strongly with hosts that contain the cofacial 7.7-diphenylnorbornane subunit than with similar hosts that have a 1,1-diphenylcyclohexane subunit. On the other hand, the value of the edge-to-face aromatic interactions calculated for our complexes (-0.2 +/- 0.6 kJmol(-1)) is significantly lower (by a factor of seven) than the one previously reported in the literature. This result highlights the importance of entropic factors in the determination of weak noncovalent interactions.

A new highly efficient synthetic route to enantiopure 10-bromocamphor

Abstract A new enantiospecific synthetic route to the interesting chiral synthetic intermediate 10-bromocamphor starting from readily available camphor is described. The procedure takes place straightforwardly in only three synthetic steps with high overall yield. Mechanistically, two interesting enantiospecific Wagner–Meerwein rearrangements involving 2-norbornyl carbocations take place during the process.