The Stereoselective Synthesis of Disubstituted E,Z-Diene Ester

The new method for the stereoselective synthesis of disubstituted diene ester was successfully applied to a highly stereoselective synthesis of E, Z-diene ester (1).     

Stereoselective total synthesis and stereochemistry of diplodiatoxin,a mycotoxin from diplodia maydis

The stereochemistry of diplodiatoxin has been deduced, and the assumed stereostructure has been confirmed by the synthesis using highly stereocontrolled strategy, in which the intramolecular Diels-Alder reaction of a(E, E, E)-triene is involved.     

Organocatalytic asymmetric synthesis of 3-difluoroalkyl 3-hydroxyoxindoles

We report the first example of highly enantioselective organocatalytic synthesis of 3-difluoroalkyl substituted 3-hydroxyoxindoles. The total synthesis of the difluoro analogue of convolutamydine E was achieved by this method.     

Total synthesis of amphidinolide E

A convergent and highly stereocontrolled synthesis of amphidinolide E (1) has been accomplished. The synthesis features a highly diastereoselective (>20:1) BF3.Et2O promoted [3+2] annulation reaction between aldehyde 3 and allylsilane 4 to afford substituted tetrahydrofuran 2.     

Total synthesis of (+)-thiazinotrienomycin E

[formula: see text] The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved. The synthesis features a highly efficient construction of the aromatic fragment 3 incorporating TBS protection of the aniline, a significantly improved synthesis of (-)-19, an intermediate employed in our trienomycins A and F total syntheses, application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit, an efficient union of 3 and (+)-4, and Mukaiyama macrolactamization to access the thiazinotrienomycin macrolide.     

Studies on the synthesis of pectenotoxin II: synthesis of a C(11)-C(26) fragment precursor via [3 + 2]-annulation reactions of chiral allylsilanes

[see reaction]. A synthesis of tetracycle 2 corresponding to the C(11)-C(26) fragment of pectenotoxin II is described. The synthesis features two highly stereoselective [3 + 2]-annulation reactions of chiral allylsilanes, generated via allylboration of aldehydes with the chiral gamma-silylallylborane 4 or the gamma-silylallylboronate 19, for construction of the highly substituted C and E rings.     

De novo asymmetric syntheses of muricatacin and its analogues via dihydroxylation of dienoates

A short and highly efficient route to both enantiomers of muricatacin as well as the C-5-epimer has been developed. The key to the overall transformation is the highly regio- and enantioselective Sharpless asymmetric dihydroxylation of an (E,Z)-dienoate. The highly efficient stereoselective synthesis prepares (-)-muricatacin in seven steps and 66% overall yield.     

Total synthesis of the anticancer natural product OSW-1

The highly potent anticancer natural saponin OSW-1 has been successfully synthesized from commercially available 5-androsten-3beta-ol-17-one 79 in 10 operations with 28% overall yield. The key steps in the total synthesis included a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation of 80 and a highly stereoselective 1,4-addition of alpha-alkoxy vinyl cuprates 68 to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total synthesis demonstrated once again the versatile synthetic applications of alpha-halo vinyl ether chemistry developed in our laboratories.     

Enantio- and diastereoselective synthesis of (E)-1,5-syn-diols: application to the synthesis of the C(23)-C(40) fragment of tetrafibricin

A highly stereoselective synthesis of (E)-1,5-syn-diols 6 is described. The kinetically controlled hydroboration of allenyltrifluoroborate 8 with Soderquist borane 2 provides the (Z)-allylic trifluoroborate 9, which undergoes sequential allylboration with two different aldehydes to provide (E)-1,5-syn-diols 6 in 72-98% yields with >95% ee and >20:1 dr. Application of this method to the synthesis of the tetrafibricin C(23)-C(40) fragment 19 is described.     

Convergent synthesis of (2R,3R,8R,9R)-N-Boc-ADDA

The convergent synthesis of N-Boc-(2R,3R,8R,9R,4E,6E)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldecadenoic acid (enantio-N-Boc-ADDA) is reported. Our flexible approach takes advantage of highly efficient non-aldol aldol and cross-metathesis methodologies.     

A highly conjunctive beta-keto phosphonate: application to the synthesis of pyridine alkaloids xestamines C, E, and H

The synthesis of a novel beta-keto gamma-xanthyl phosphonate has been achieved. This highly conjunctive reagent has been utilized in a combination of radical and ionic reactions to create new carbon-carbon bonds. Its usefulness was demonstrated by realizing the first total synthesis of naturally occurring pyridine alkaloids xestamines C, E, and H.     

Enantioselective total synthesis of convolutamydines B and E

[reaction: see text] The first enantioselective total synthesis of convolutamydines B and E has been achieved using our vinylogous Mukaiyama aldol reaction. The synthesis features highly diastereoselective vinylogous Mukaiyama aldol reaction with isatin instead of aldehydes to construct a chiral center of convolutamydines. Additionally, the absolute configuration of natural convolutamydine B has been determined as R by its CD spectrum.     

Total synthesis of cyclic diterpene tonantzitlolone based on a highly stereoselective substrate-controlled aldol reaction and ring-closing metathesis

The total synthesis of the cyclic diterpene ent-tonantzitlolone (ent-1) is presented. Key steps for assembling the macrocyclic core structure of 1 are a highly selective aldol reaction and an E selective ring-closing metathesis reaction. A detailed investigation of these two steps and the final transformations towards the completion of the synthesis is disclosed.     

Stereoselective synthesis of (E)-beta-tributylstannyl-alpha,beta-unsaturated ketones: construction of a key intermediate for the total synthesis of zoanthamine

(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.     

One-pot synthesis of (E)-styryl ketones from styrenes

A new, efficient protocol for the highly stereoselective one-pot synthesis of (E)-styryl ketones from styrenes based on sequential ruthenium-catalyzed silylative coupling-rhodium-catalyzed desilylative acylation reactions is reported.     

N-isopropylsulfinylimines as useful intermediates in the synthesis of chiral amines: expeditive asymmetric synthesis of the calcimimetic (+)-NPS R-568

An efficient and high-yielding approach for the asymmetric synthesis of calcimimetic (+)-NPS R-568 (1) has been developed. The key step of the synthesis is the highly diastereoselective addition of methyl Grignard to the (SS,E)-N-(3-methoxybenzylidene)-2-propanesulfinamide [5(S)], which afforded a single diastereoisomer in high yield in short reaction time.     

Total Synthesis of (−)‐Vindorosine

Outlined herein is a novel and scalable synthesis of (−)‐vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone‐derived lithium dienolates with indolyl N ‐tert‐butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza‐Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (−)‐vindorosine and related alkaloids.     

First stereospecific synthesis of (E)- or (Z)-alpha-fluoroenones via a kinetically controlled Negishi coupling reaction

A highly stereospecific synthesis of (E)- or (Z)-alpha-fluoro-alpha,beta-unsaturated ketones 4, via a kinetically controlled Negishi palladium-catalyzed coupling reaction, was developed, providing an easy and general access to valuable fluorinated intermediates (pharmaceutical, peptide mimic, and so on). The synthesis involved a reaction between E/Z gem-bromofluoroolefins 2 and alkoxyvinylzinc species 6 under controlled reaction temperature. At 10 degrees C, (Z)-4 (70 to 99% yields) was obtained along with unreacted (Z)-2 (66 to 99% yields). At THF reflux, the recovered olefin was transformed into (E)-4 (up to 98% yield).     

Syntheses of alpha-fluoro-alpha,beta-unsaturated thioamides and thiazolines from a fluorophosphonodithioacetate

A high-yielding synthesis of methyl fluoro(diethoxyphosphono)dithioacetate starting from its difluorinated analogue is reported. Fluorophosphonothioacetamides and -methylthiazolines, prepared from this new dithioester, have been successfully transformed into highly functionalized fluoroalkenes. Good stereoselectivity in favor of the E isomer was observed from the fluorophosphonomethylthiazolines. The potential of these new fluorinated olefinating reagents for the synthesis of modified peptides and glycosides is also disclosed.