Santiago Rodríguez

Stereoselective Synthesis of the Naturally Occurring Lactones(−)-Osmundalactone and (−)-Muricatacine Using Ring-Closing Metathesis

The stereoselective synthesis of the naturally occurring lactones osmundalactone (−)-1 and muricatacin (−)-2 is described. The key steps in each synthesis are the stereoselective addition of a Grignard reagent to a suitably protected α-hydroxy aldehyde and a ring-closing metathesis. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Stereoselective synthesis of (−)-malyngolide, (+)-malyngolide and (+)-tanikolide using ring-closing metathesis

Abstract The stereoselective syntheses of the naturally occurring δ-lactones (+)-tanikolide and (−)-malyngolide as well as of the unnatural (+)-enantiomer of the latter are described. Key steps in each of these syntheses were stereoselective additions of organometallic reagents to α-oxygenated ketones and olefin ring-closing metatheses.

Stereoisomerization of β-Hydroxy-α-sulfenyl-γ-butyrolactones Controlled by Two Concomitant 1,4-Type Nonbonded Sulfur−Oxygen Interactions As Analyzed by X-ray Crystallography

We have synthesized nine beta-hydroxy-alpha-sulfenyl-gamma-butyrolactones having different substituents. The syn-anti or syn-syn lactones (or any mixture of both) invariably isomerized into syn-anti/syn-syn lactones in a ratio of approximately 6/4. The other two possible isomeric lactones (anti-syn or anti-anti) were never observed. The crystal structures of syn-syn lactones have been determined. We found sulfur-oxygen distances to be less than the sum of the van der Waals radii (3.3 A), with the angle formed among the hydroxylic oxygen, sulfur, and quaternary aromatic carbon being close to 180 degrees. In addition, carbonylic oxygen-sulfur is directed <40 degrees from the perpendicular to the C-S-C. Theoretical calculations were performed which emphasize the directionality of the sulfur-oxygen interaction. The X-ray and theoretical studies demonstrate that two concomitant, attractive 1,4 intramolecular interactions of divalent sulfur with both carbonyl and hydroxyl oxygens are the driving force for the aforementioned stereochemical preference. Then nonbonded sulfur-oxygen interactions would control the stereoselectivity of the reaction. The same features are observed in the X-ray structure of a beta-hydroxy-alpha-sulfinyl-gamma-butyrolactone.

Synthesis of conjugated γ- and δ-lactones from aldehydes and ketones via a vinylation(allylation)-ring closing metathesis–oxidation sequence

Abstract Nucleophilic C-vinylation and C-allylation of aldehydes and ketones followed by O-allylation of the obtained carbinols gave the corresponding allyl or homoallyl ethers, respectively. Ring-closing metathesis of these compounds afforded in many cases cyclic ethers (dihydrofurans and dihydropyrans, respectively) bearing disubstituted and trisubstituted CC bonds. These were then subjected to allylic oxidation to yield conjugated γ- and δ-lactones. Reasons for the observed failures are presented and discussed.

Synthesis of conjugated δ-lactams using ring-closing metathesis

Abstract Addition of allyl magnesium or metallyl magnesium bromide to the N -benzyl imines of benzaldehyde and cyclohexanone, followed by acylation with acryloyl or metacryloyl chloride provided the corresponding α,β-unsaturated amides. Ring-closing metathesis of the latter with ruthenium catalyst PhCHRuCl 2 (PPh 3 ) 2 in the presence of Ti(O i Pr) 4 provided excellent yields of the corresponding conjugated δ-lactams with both disubstituted and trisubstituted CC bonds. Some specific trisubstitution patterns, however, as well as tetrasubstituted CC bonds, were not obtained. In these cases, even the use of a second generation, imidazolylidene-substituted ruthenium catalyst at high temperature did not lead to success.

Nitroepoxides as Versatile Precursors to 1,4-Diamino Heterocycles

Nitroepoxides are easily transformed into 1,4-diamino heterocycles such as quinoxalines and pyrazines by treatment with 1,2-benzenediamines and ammonia, respectively. Additionally, related saturated heterocycles, such as piperazines and tetrahydroquinoxalines, can be accessed by treatment with 1,2-diamines and a reducing agent. These transformations are efficient, provide access privileged, bioactive structures, and produce minimal waste.

Regioselective Ring Opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride

Efficient ring opening of 3,4-epoxyesters with alcohols to produce 4-alkoxy-3-hydroxyesters and their isomerization into 4-ketoesters using boron trifluoride as the catalyst are presented. Both transformations are simple and efficient methods for the synthesis of the above named synthetically useful compounds.

Dynamic Kinetic Asymmetric Ring-Opening/Reductive Amination Sequence of Racemic Nitroepoxides with Chiral Amines: Enantioselective Synthesis of Chiral Vicinal Diamines

We report a highly diastereoselective synthesis of vicinal diamines by the treatment of nitroepoxides with primary amines and then a reducing agent. When using a chiral primary amine, racemic nitroepoxides are transformed into chiral diamines as a single enantiomers (>95:5 er) through a dynamic kinetic asymmetric transformation (DYKAT). The overall process is a one-pot procedure combining the exposure of nitroepoxides to chiral amines to afford diastereomeric mixtures of aminoimines and subsequent stereoselective imine reduction.

A stereoselective synthesis of (+)-malyngolide via a ring-closing olefin metathesis

Abstract A very short and stereoselective synthesis of the non-natural enantiomer of malyngolide from l -erythrulose is described. Key features of the synthesis are the Felkin–Anh diastereoselective allylation of a polyoxygenated ketone and the allylation/metathesis/allylic oxidation protocol recently described by our group.

Stereoselective synthesis of α-substituted serines from protected erythrulose oximes

Abstract The additions of organolithium reagents to the CN bond of several chiral oxime ethers derived from erythrulose afforded protected amino polyols with high diastereoselectivity. Four of the latter compounds have been converted into the α,α-disubstituted α-amino acids ( R )-2-(−)-methylserine, ( S )-2-(+)-methylserine, ( R )-(+)-2-phenylserine and ( R )-(−)-2- n -butylserine.