Miguel A. Ramírez

Stereocontrolled synthesis of cyclic ethers by intramolecular hetero-Michael addition. 3. Enantiomeric synthesis of highly functionalized and fused tetrahydropyrans

Abstract A methodology based on intramolecular hetero-Michael addition of properly functionalized alkoxy-γ-benzoyloxy-α,β-unsaturated esters for the synthesis of highly substituted and fused poly-tetrahydropyran nuclei of marine polyether toxins with absolute control of all the stereocentres is described.

Enantiomeric synthesis of endo-substituted tetrahydropyrans

Abstract A general procedure for the enantiomeric synthesis of 3-hydroxy-2-alkyl-tetrahydropyran benzoates with absolute stereochemical control by using a new intramolecular diastereoselective cyclization of chiral hydraxy-α,β-chiral unsaturated esters is reported.

A Microwave‐Assisted Domino Rearrangement of Propargyl Vinyl Ethers to Multifunctionalized Aromatic Platforms

This research was supported by the Spanish MICINN and the European RDF (CTQ2008-06806-C02-01 and CTQ2008-06806-C02-02), the Spanish MSC ISCIII (RETICS RD06/0020/1046), FUNCIS (REDESFAC PI01/06). G.M.A. and L.C. thank the Spanish MEC for FPU and FPI grants, respectively. The authors thank Dr. T. Martin and Professor V. S. Martin for insightful discussions, Professor F. Cossio for mechanistic advice, and Anna Jurado for technical assistance.

Iron(III)-Catalyzed Consecutive Aza-Cope−Mannich Cyclization: Synthesis of trans-3,5-Dialkyl Pyrrolidines and 3,5-Dialkyl-2,5-dihydro-1H-pyrroles

An efficient alkene aza-Cope-Mannich cyclization between 2-hydroxy homoallyl tosylamine and aldehydes in the presence of iron(III) salts to obtain 3-alkyl-1-tosyl pyrrolidines in good yields is described. The process is based on the consecutive generation of a γ-unsaturated iminium ion, 2-azonia-[3,3]-sigmatropic rearrangement, and further intramolecular Mannich reaction. Iron(III) salts are also shown to be excellent catalysts for the new aza-Cope-Mannich cyclization using 2-hydroxy homopropargyl tosylamine.

Iron(III) catalyzed direct synthesis of cis-2,7-disubstituted oxepanes. The shortest total synthesis of (+)-isolaurepan.

Prins cyclization of bis-homoallylic alcohols with aldehydes catalyzed by iron(III) salts shows excellent cis selectivity and yields to form 2,7-disubstituted oxepanes. The iron(III) is able to catalyze this process with unactivated olefins. This cyclization was used as the key step in the shortest total synthesis of (+)-isolaurepan.

Factors Controlling the Alkyne Prins Cyclization : The Stability of Dihydropyranyl Cations

The relative stability of the intermediates involved in the alkyne Prins cyclization and the competitive 2-oxonia-[3,3]-sigmatropic rearrangement was studied. This rearrangement was shown to occur slowly under typical alkyne Prins cyclization conditions when the allenyl oxocarbenium ion that results from the rearrangement is similar to or higher in energy than the starting alkynyl oxocarbenium ion. The formal 2-oxonia-[3,3]-sigmatropic rearrangement may be disfavored by destabilizing the resultant allenyl oxocarbenium ion or by stabilizing an intermediate dihydropyranyl cation. The trimethylsilyl group as a substituent at the alkyne and electron-withdrawing groups (CH2Cl and CH2CN) located at the alpha-position to the carbinol center are shown to be effective. DFT calculations suggest that these substituents stabilize the dihydropyranyl cations, thus leading to a more uniform reorganization of the electronic density in the ring, and do not have a direct effect on the formally positively charged carbon atom.

Total synthesis of 8-desoxy-isocaespitol, A new polyhalogenated sesquiterpene from Laurencia caespitosa☆

Abstract The structure of a new polyhalogenated bisabolene-type sesquiterpene, 2 , isolated from Laurencia caespitosa has been elucidated by chemical and spectral means and confirmed by a three-step synthesis starting from commercial farnesol.

Total synthesis of obtusenol

Abstract The total synthesis of obtusenol ( 9 ), a dibrominated sesquiterpene isolated from the red alga Laupencia obtusa , has been achieved by a three-step synthesis starting from commercial farnesol.

An example of a chiral non-racemic carbanion as versatile synthon in the asymmetric synthesis of polysubstituted γ-lactones

Abstract The application of a chiral non-racemic carbanion generated from enantiomerically enriched α-sulfonyl-γ-lactones to the asymmetric synthesis of highly substituted and fused γ-lactones is described.

Enantiodivergent Synthesis of (+)- and (-)-Pyrrolidine 197B: Synthesis of trans-2,5-Disubstituted Pyrrolidines by Intramolecular Hydroamination.

A highly efficient, diastereoselective, iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving α-substituted amino alkenes is described. Thus, enantiopure trans-2,5-disubstituted pyrrolidines and trans-5-substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l-α-amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (-)-pyrrolidine 197B alkaloids from l-glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.