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Biomedical subjects

Barry M Trost

Publications and source records attributed to Barry M Trost.

118 records · Page 7Linked to original sources
PubMed2002

A synthesis of trisubstituted alkenes by a Ru-catalyzed addition.

Catalyzed by ruthenium trisacetonitrile hexafluorophosphate 4, the Alder-ene type reaction of alkenes and internal alkynes provides an effective way to synthesize trisubstituted alkenes. Unlike most typical olefination protocols, this reaction is atom economical, and affords trisubstituted alkenes with defined olefin geometry. The regioselectivity can be explained invoking a steric argument based on the proposed mechanism. The first C-C bond formation generally involves sterically less hindered carbons of the alkenes and alkynes. Modest to very high regioselectivity can be achieved depending on the steric difference of the two substituents of alkynes.

Alkenes↗
PubMed2002

Mechanistic dichotomy in CpRu(CH(3)CN)(3)PF(6) catalyzed enyne cycloisomerizations.

Enynes are easily accessible building blocks as a result of the rich chemistry of alkynes and thus represent attractive substrates for ring formation. A ruthenium catalyst for cycloisomerization effects such reaction of 1,6- and 1,7-enynes typically at room temperature in acetone or DMF under neutral conditions. The reaction is effective for forming five- and six-membered rings of widely divergent structure. The alkyne may bear both election-donating and election-withdrawing substituents. The alkene may be di- or trisubstituted. Introduction of a quaternary center at the propargylic position of an ynoate, however, completely changes the nature of the reaction. In the case of a 1,6-enynoate, a seven-membered ring forms in excellent yield under equally mild conditions. Evidence is presented to indicate a complete change in mechanism. In the former case, the reaction involves the intermediacy of a ruthenacyclopentene. In the latter case, a C-H insertion to form a pi-allylruthenium intermediate is proposed and supported by deuterium-labeling studies. A rationale is presented for the structural dependence of the mechanism.

Alkynes↗
PubMed2002

An unusual ruthenium-catalyzed cycloisomerization of alkynes and propargyl alcohols.

CpRu(NCCH3)3+PF6- catalyzes the cycloisomerization of diyne-ols to alpha,beta,gamma,delta-unsaturated aldehydes and ketones in good-to-excellent yields. 1-Hydroxy-2,7-diynes and 1-hydroxy-2,8-diynes can be utilized to form highly functionalized five- and six-membered rings, respectively. Tertiary as well as secondary propargyl alcohols are cycloisomerized to a single isomeric product. A wide variety of tether substitution can be tolerated. Even totally unsubstituted tethers can be employed, as geminal disubstituents are not required for cyclization. Additional hydroxyl substituents at an alternative "internal" propargylic position are eliminated during the reaction-a feature that leads to a convenient cyclopentadiene synthesis. Furthermore, 3-hydroxy-1,6-diynes also can be cyclized to form cross-conjugated aldehydes.

Alkynes↗
PubMed2002

A Ru catalyzed divergence: oxidative cyclization vs cycloisomerization of bis-homopropargylic alcohols.

During the course of investigating the development of catalytic reactions involving ruthenium vinylidene intermediates, a novel divergence of reactivity was discovered. The oxidative cyclization of bis-homopropargylic alcohols with Ru(+2) complexes as catalysts and N-hydroxysuccinimide as oxidant, which requires formation of a ruthenium vinylidene intermediate, is complicated by the simple electrophilically initiated direct attack of the hydroxyl group on a pi-complex of the alkyne and ruthenium. A catalytic system composed of CpRu[(p-CH(3)O(6)H(4))(3)P](2)Cl and excess (p-CH(3)O-C(6)H(4))(3)P directs the reaction toward the oxidative cyclization to form delta-lactones in good yields. Significantly, a simple switch of catalyst to CpRu[(p-FC(6)H(4))(3)P](2)Cl redirects the reaction to a cycloisomerization to form dihydropyrans in good yields. The synthetic utility of the oxidative cyclization is illustrated by the synthesis of oviposition attractant pheromone of the mosquito Culex pipens. The utility of the cycloisomerization to dihydropyrans is demonstrated by an iterative process leading to the antiviral agent narbosine B. A rationale for this dramatic switch by simple ligand modification is proposed.

Alkynes↗
PubMed2002

Application of the AAA reaction to the synthesis of the furanoside of C-2-epi-hygromycin A: a total synthesis of C-2-epi-hygromycin A.

A strategy for stereocontrolled syntheses of furanoside type of natural products is developed for a glycosyl aryl ether. This strategy resolves the issue of low diastereoselectivity typical of normal glycosidation methods for furanosides. All the stereochemistry ultimately derives from a desymmetrization of a 2,5-diacyloxy-2,5-dihydrofuran using Pd catalyzed asymmetric allylic alkylation which sets both the absolute stereochemistry and 1,4-relative stereochemistry. Diastereo-controlled elaboration of the 3,4-double bond then completes the synthesis. A new conjunctive reagent, 1-nitro-1-phenylsulfonyl-ethane, is developed to serve as an acyl anion equivalent. The utility of a phenol as a nucleophile in the Pd catalyzed glycosylation is demonstrated. From this strategy emerged a short, practical synthesis of C-2-epi-hygromycin A.

Aldehydes↗
PubMed2002

On inventing reactions for atom economy.

An important first step in making organic reactions more environmentally benign by design requires processes that are, to a first approximation, simple additions with anything else needed only catalytically. Since so few of the existing reactions are additions, synthesis of complex molecules requires the development of new atom-economic methodology. The prospect for such developments is probed in the context of ruthenium-catalyzed reactions. Using mechanistic reasoning, over 20 new processes of varying complexity have been designed and implemented. While some involved oxidation-reduction processes, most involved C-C bond-forming reactions.

Alkenes↗
PubMed2002

Pd asymmetric allylic alkylation (AAA). A powerful synthetic tool.

Palladium catalyzed asymmetric allylic alkylations represent a challenging problem because the mechanism of the reaction places the chiral environment distal to the bond breaking or making events responsible for the asymmetric induction. Furthermore, unlike virtually every other asymmetric process, many strategies can be employed for introduction of asymmetry and many different types of bonds can be formed. While over 100 different ligands have been designed, a family of ligands derived from 2-diphenylphosphinobenzoic or 1-naphthoic acid and chiral scalemic diamines have been successful in inducing excellent enantioselectivity by five different enantiodiscriminating events. These methods have already provided practical strategies towards numerous biological targets--some of which are adenosine and its enantiomer, aflatoxin B, aristeromycin, calanolide A and B, carbovir, cyclophellitol, ethambutol, galanthamine, mannostatin, neplanocin, phyllanthocin, sphingofungins E and F, tetraponaines, vigabatrin, and valienamine.

Alkylation↗