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Barry M Trost

Publications and source records attributed to Barry M Trost.

At least 73 records · Page 4Linked to original sources
PubMed2004

Asymmetric allylic alkylation, an enabling methodology.

The diversity of mechanisms for enantiodiscrimination and of bond types that can be formed make Pd-catalyzed asymmetric allylic alkylation a powerful key step for simplification of synthetic strategy to complex molecular targets. Using a wide range of different classes of compounds including alkaloids, polyhydrofurans, nucleosides and carbanucleosides, cyclohexitols and cyclopentitols, chromanes, cyclopentanoids, amino acids, barbiturates, etc., novel synthetic strategies emerge that provide short efficient asymmetric syntheses.

Alkaloids↗
PubMed2004

Pd-catalyzed carbonylative lactamization: a novel synthetic approach to FR900482.

An asymmetric synthesis of the benzazocine core of FR900482 has been achieved in 15 steps from 3,5-dinitro-p-toluic acid. Key features of the synthesis include an enantioselective N-methylephedrine-mediated zinc acetylide addition to a highly enolizable arylacetaldehyde and a novel Pd-catalyzed carbonylative lactamization to form an eight-membered ring. [reaction--see text]

Catalysis↗
PubMed2004

A "chiral aldehyde" equivalent as a building block towards biologically active targets.

Chiral gamma-aryloxybutenolides, readily accessible through dynamic kinetic asymmetric transformation (DYKAT) of racemic acyloxybutenolides, were utilized as "chiral aldehyde" building blocks for intermolecular cycloadditions and Michael reactions. Unprecedented selectivity in trimethylenemethane cycloadditions with this building block allowed an efficient synthesis of a novel metabotropic glutamate receptor 1 antagonist in development by the Bayer corporation. These studies further inspired work that culminated in the total synthesis of (+)-brefeldin A, a natural product with a range of significant biological properties. All of the stereochemistry in this target molecule was derived from two palladium-catalyzed asymmetric allylic alkylation reactions. The trans-alkenes were synthesized by a Julia olefination and a ruthenium-catalyzed trans-hydrosilylation-protodesilylation protocol. The route to (+)-brefeldin A lends itself to analogue syntheses and was completed in 18 steps in 6 % overall yield.

Aldehydes↗
PubMed2004

Structure elucidation of (+)-amphidinolide a by total synthesis and NMR chemical shift analysis.

The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of NMR chemical shift analysis and total synthesis. Using the reported structure as a starting point, a number of diastereomers of amphidinolide A were prepared. The deviations of the chemical shifts of key protons in each isomer relative to the values reported for the isolated material were used to determine the locations of the errors in relative stereochemistry. The spectroscopic data for our proposed structure of (+)-amphidinolide A and the isolated material are in excellent agreement. The key step, a [Cp*Ru(MeCN)3]PF6-catalyzed alkene-alkyne coupling, was used to form the 20-membered ring in the final step of the synthesis.

Animals↗
PubMed2004

An asymmetric synthesis of hamigeran B via a Pd asymmetric allylic alkylation for enantiodiscrimination.

A protocol for the asymmetric allylic alkylation of a five-membered ring ketone derivative that employs the lithium enolate in the presence of lithium alkoxides gave high yields and enantioselectivities. This product serves as a versatile intermediate as demonstrated in a convergent total synthesis of the antiviral agent hamigeran B. The sequence involves two unusual observations. In the intramolecular Heck reaction which establishes the complete ring sytem, the beta-H elimination step occurs both endocyclic (as expected) and exocyclic, the latter most surprising since it creates an exocylic tetrasubstituted double bond. In the catalytic hydrogenation, use of Pd/C gives complete selectivity for net delivery of hydrogen to the most hindered face of the substrate, whereas use of Ir black gives complete selectivity for delivery of hydrogen to the least hindered face. Such unusual behavior speaks to the unusual chemical properties associated with hamigeran B which may be relevant to its biological activity.

Alkylation↗
PubMed2004

Direct catalytic asymmetric aldol additions of methyl ynones. Spontaneous reversal in the sense of enantioinduction.

In this Communication, we report the direct, catalytic, asymmetric aldol addition of methyl ynones using our dinuclear zinc catalyst. A spontaneous reversal in the sense of enantioinduction was observed for these reactions; formation of the (S)-enantiomer is favored in the early stages (69% ee after 5 min), whereas the (R)-enantiomer is isolated as the major product after prolonged reaction times (97% ee after 22 h). It could be shown that this reversal in enantioselectivity is due to formation of a new catalytic species which incorporates the aldol product.

Alcohols↗
PubMed2004

Asymmetric catalysis: an enabling science.

Chirality of organic molecules plays an enormous role in areas ranging from medicine to material science, yet the synthesis of such entities in one enantiomeric form is one of the most difficult challenges. The advances being made stem from the convergence of a broader understanding of theory and how structure begets function, the developments in the interface between organic and inorganic chemistry and, most notably, the organic chemistry of the transition metals, and the continuing advancements in the tools to help define structure, especially in solution. General themes for designing catalysts to effect asymmetric induction are helping to make this strategy more useful, in general, with the resultant effect of a marked enhancement of synthetic efficiency.

Alkylation↗
PubMed2004

5H-oxazol-4-ones as building blocks for asymmetric synthesis of alpha-hydroxycarboxylic acid derivatives.

5H-Alkyl-2-phenyl-oxazol-4-ones, a little-known heterocyclic ring system, are readily available via a microwave-assisted, sodium fluoride catalyst cyclization of mono-alpha-haloimides, which in turn are accessed by N-acylation of benzamides with alpha-bromo acid halides. Terminally substituted allyl systems serve as excellent substrates for Mo-catalyzed asymmetric allylic alkylation. The resultant products are formed with excellent ees involving a catalyst derived from N,N'-bis-picolinamide of trans-1,2-diaminocyclohexane and cycloheptatriene molybdenum tris(carbonyl). In addition to benzenoid, nonbenzenoid aromatic and vinyl substituents on the allyl carbonate moiety provide good to excellent regio- and diastereoselectivity as well as excellent enantioselectivity. Substituents on the heterocycle include methyl, n-butyl, allyl, isobutyl, isopropyl, and cyclohexyl. The presence of a double bond in the product allows them to be further modified via the chemistry of the double-bond, including metathesis. The products are hydrolyzed under basic conditions to provide alpha-hydroxyamides.

Alcohols↗
PubMed2004

A formal synthesis of (-)-mycalamide A.

Novel strategies are developed for an efficient formal synthesis of (-)-mycalamide A. The left-hand side (-)-7-benzoylpederic acid is synthesized from (2S,3S)-2,3-epoxybutane. The key features include a highly regioselective Ru-catalyzed alkene-alkyne coupling reaction and a novel way to control the challenging C(7) stereocenter. The right-hand side was synthesized from (R)-pantolactone. The complex trioxodecalin core is constructed with two Pd(0)-catalyzed O-pi-allyl cyclizations. The first one is chemoselective, while the second one is highly diastereoselective. Three additional steps would be required to complete a total synthesis of (-)-mycalamide A.

Animals↗
PubMed2003

Total syntheses of furaquinocin A, B, and E.

A modular approach to the total synthesis of furaquinocins culminated in the total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck cyclization allows the enantio- and diastereoselective construction of dihydrobenzofuran 32. Introduction of a double unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the naphthoquinone with squaric acid based methodology leads to furaquinocin E. The use of differentially substituted squaric acid derivatives allows the synthesis of three analogues of furaquinocin E. The additional stereocenters in furaquinocin A and B can be introduced with a diastereoselective Sakurai allylation. The stereoselective elongation of the side chain is possible using cross metathesis or ring closing metathesis. The obtained late-stage intermediates were successfully transformed to furaquinocin A and B.

Benzofurans↗
PubMed2003

Dynamic kinetic asymmetric cycloadditions of isocyanates to vinylaziridines.

The first examples of the use of racemic vinylaziridines in a Pd-catalyzed dynamic kinetic asymmetric transformation have been examined. Optimization studies of the Pd-catalyzed addition of vinylaziridines to isocyanates revealed that the chiral ligand between trans-1,2-diaminocyclohexane and 2-diphenylphosphino-1-naphthoic acid is superior to that involving 2-diphenylphosphino benzoic acid. Surprisingly, high ee's required the use of an acid whose pKa was about 4.7 +/- 0.1 as a cocatalyst. Both acetic acid and hydroxybenzotriazole meet this requirement. Less electrophilic isocyanates (e.g., benzyl, p-methoxyphenyl) gave higher ee's than more electrophilic ones (phenyl or benzoyl). Both N-benzyl and N-arylaziridines react well to give good yields and ee's, whereas N-tosylaziridines gave lower ee's. A 1,1-disubstituted aziridine led to the formation of a tertiary C-N bond with ee's comparable to the formation of the secondary C-N bond. The products were easily reduced almost quantitatively to the sensitive imidazolidines which can be readily hydrolyzed to the vicinal diamines. The reactivity pattern is consistent with a Curtin-Hammett situation wherein the enantiodiscriminating event is the cyclization of a rapidly equilibrating dynamic pi-allyl palladium intermediate.

Aziridines↗
PubMed2003

A theoretical study on the mechanism, regiochemistry, and stereochemistry of hydrosilylation catalyzed by cationic ruthenium complexes.

Density functional calculations have been carried out to understand the anti-addition stereochemistry and Markovnikov regiochemistry of the hydrosilylation of terminal alkynes and the endo-dig product of intramolecular hydrosilylation of homopropargyl alcohols catalyzed by cationic cyclopentadienyl-ruthenium complexes. It has been found that hydride or silyl insertion is concerted with the oxidative addition of the H-Si bond. Hydride insertion is much more favorable than silyl insertion. Such a hydride insertion nicely reproduces the observed regioselectivity, while silyl insertion would predict the opposite result. The hydride insertion leads to the formation of a eta(2)-vinylruthenium intermediate for the reaction of acetylene or a metallacyclopropene intermediate for the reaction of propyne. In the formation of both intermediates, there is a C(alpha)-C(beta) bond rotation so that the transferring hydride becomes anti to the silyl group. This is followed by a facile reductive alpha-silyl migration transition state, which results in the overall anti-addition stereochemistry. The proposed mechanism also rationalizes the observed regio- and stereochemistry of the intramolecular reaction.

Journal Article↗
PubMed2003

A mechanistic dichotomy in ruthenium-catalyzed propargyl alcohol reactivity: a novel hydrative diyne cyclization.

The cycloisomerization of diyne-ols catalyzed by [CpRu(CH3CN)3]PF6 to 2-vinyl-1-acylcycloalkenes proceeds via a ruthenacyclopentadiene involving initial ionization of the tertiary or secondary alcohol, followed by readdition. In the case of primary alcohols, a competing pathway wherein water first adds would appear to occur. The feasibility of this proposed minor pathway was tested in the reaction of diynes in the presence of water. Quite excitingly, cyclization comcommittant with addition of water to form 1-acylcycloalkenes occurs. This proves to be general process to form five- and six-membered rings. Interestingly, hydrative cyclization of Z-5-decen-2,8-diyne to 1-acetyl-2-ethyl-cyclohexa-1,4-diene occurs without isomerization of the double bonds. Furthermore, the epoxide of the same substrate cyclizes without opening of the strained epoxide. Unsymmetrically substituted diynes cyclize with remarkable chemoselectivity wherein water attacks the less hindered alkynes. beta-branching of any kind gives only a single product. Remarkably, even competing methyl versus ethyl still effects a 2.5:1 selectivity in favoring water addition to the methyl-bearing alkyne. Alcohols can replace water and provide enol ethers. Strong mechanistic evidence suggests two reaction manifolds indeed operate, depending upon the presence of propargyl alcohols and the degree of substitution on the hydroxyl-bearing carbon.

Alkynes↗