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Substituted oxocene derivatives have been synthesized by Lewis acid catalyzed reactions of ε-hydroxy-alkene and substituted aromatic aldehydes. The Cu(OTf)2-bis-phosphine catalyzed reaction typically provides substituted dihydropyran derivatives through an olefin-migration, followed by a Prins cyclization. The corresponding reaction catalyzed by TMSOTf or BF3·OEt2 provided eight-membered cyclic ethers, oxocenes, selectively. This methodology provides convenient access to a variety of 2,4,8-trisubstituted oxocenes in good yields and excellent diastereoselectivities.

Polystyrene-supported palladium(0) (Pd@PS) nanoparticles as a heterogeneous catalyst have been developed for caboxylation of aryl halides, alkenylsilanes, and organoboronic acids to produce the corresponding carboxylic acids with minor quantities of corresponding aldehydes using bench-stable and inexpensive oxalic acid as the C1 source under focused microwave irradiation. The close vicinity of oxalic acid to Pd@PS maintained through ionic bonding helped to produce CO2 over the catalytic surface that concurrently participated in the carboxylation reaction.

An organocatalytic asymmetric cascade Michael/hemiketalization/retro-aldol reaction between unsaturated pyrazolones and α-nitroketones is described. A bifunctional thiourea catalyst was found to be efficient for this reaction. With 10 mol % of catalyst, high yields as well as excellent enantioselectivities are attained for a variety of 3-acyloxy pyrazoles under mild reaction conditions.

An enantioselective total synthesis of GEX1Q1 has been accomplished in a convergent manner. The C-5 asymmetric center has now been assigned through synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over its C-5 epimer. The salient features of this synthesis include an asymmetric hetero-Diels-Alder reaction to construct the tetrahydropyran ring and a Suzuki cross-coupling to assemble the key segments. © 2014 American Chemical Society.

An enantioselective total synthesis of (+)-amphirionin-4 has been accomplished in a convergent manner. The synthesis features an efficient enzymatic lipase resolution to access the tetrahydrofuranol core in optically-active form. The functionalized tetrahydrofuran derivative was synthesized via an oxocarbenium ion-mediated highly diastereoselective syn-allylation reaction. The polyene side chain was synthesized using Stille coupling reactions. Nozaki-Hiyama-Kishi coupling was utilized to construct the C-8 stereocenter and complete the synthesis of (+)-amphirionin-4.

An enantioselective synthesis of (+)-lithospermic acid, a potent anti-HIV agent, has been accomplished in a convergent manner in nine steps. The synthesis features an enantioselective intramolecular oxa-Michael addition catalyzed by a quinidine derivative, a hypervalent iodine-mediated rearrangement of chromanone to dihydrobenzofuran, an enantioselective α-oxyamination, and an intermolecular C-H olefination.

An enantioselective total synthesis of zampanolide has been accomplished using a novel DDQ/Brønsted acid promoted cyclization as the key reaction. The synthesis features cross-metathesis to construct the trisubstituted olefin and a ring-closing metathesis to form the macrolactone. The final N-acyl aminal formation was stereoselectively accomplished by an organocatalytic reaction.

An enantioselective total synthesis of (+)-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A.

An enantioselective route to the oxatetracyclic core of (-)-platensimycin (1) has been investigated by using an intramolecular Diels-Alder reaction as the key step. The thermal reaction of E/Z mixture (1:1) provided oxatetracyclic core 2 from the E-diene and the Z-diene was recovered unchanged. The Diels-Alder substrate was conveniently assembled in optically active form with use of (S)-carvone as the starting material.

[structure: see text] An enantioselective total synthesis of (-)-lasonolide A is described. The upper tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The bicyclic isooxazoline led to the tetrahydropyran ring as well as the quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels-Alder reaction as the key step. Three stereocenters were enantioselectively installed in this single step reaction.

© 2014 American Chemical Society. An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.

TiCl(4)-promoted multicomponent reactions involving N-tosyl imino ester, cyclic enol ether, and silane reagents in a single one-pot operation provide functionalized alpha-amino acids with multiple stereogenic centers in good to excellent yields. Cis/trans selectivities with optically active substituted dihydrofurans have been investigated.

Aldol reaction of the Ti-enolate derived from cis-1-tosylamido-2-indanyl chloroacetate with representative aldehydes proceeded in excellent yield and high diastereoselectivities. Removal of chlorine provided alternative access to highly diastereoselective acetate aldol equivalents or the corresponding glycidic ester condensation products. [reaction: see text]

[structure: see text] An enantioselective total synthesis of (-)-spongidepsin (2) and elucidation of the absolute stereochemistry of its four stereocenters are described. Spongidepsin (2), a 13-membered depsipeptide isolated from the Vanuatu marine sponge Spongia sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis.

[reaction: see text] anti-Aldol reaction of Ti-enolate derived from cis-2-arylsulfonamido-1-acenaphthenyl propionate with representative aldehydes proceeded in excellent yield with high diastereoselectivity. Both enantiomers of cis-2-amino-1-acenaphthenol were synthesized employing lipase-catalyzed kinetic resolution as the key step.

[structure: see text]. An efficient and highly stereoselective synthesis of the gastroprotective natural product AI-77-B is described. The stereocenters of the hydroxy amino acid moiety were generated by an ester-derived titanium-enolate-mediated syn-aldol reaction, a Curtius rearrangement, and application of Dondoni's aldehyde homologation. Condensation with the dihydroisocoumarin fragment and subsequent deprotecting transformations furnished optically active AI-77-B.

A unique synergistic combination of lipase and ionic liquid [hmim]Br is reported for metal-free H(2)O(2) activation, which is the first example of biocatalytic promiscuity of CAL-B for chemoselective oxidation of aryl alcohols/acetates. The catalytic system exhibits excellent functional group compatibility under neutral conditions besides reusability up to ten cycles thereby making the process economically and environmentally viable.

Resin immobilized stable, spherical CuO nanoparticles prepared in the presence of cyclodextrin (CD) act as catalysts for liquid phase alcohol oxidation in air. The catalytic activity of the CuO nanocomposites and its green chemistry approach make it superior to the related resin-bound Cu(0) nanocomposite. The effect of alcohol chain length and electron-donating or -withdrawing groups influence product yield. The nanocomposites exhibit good reusability, simple workup procedure, and a straightforward approach to aldehyde formation.

An enantioselective and convergent total synthesis of pladienolide B (1) is described. Pladienolide B binds to the SF3b complex of a spliceosome and inhibits mRNA splicing activity. The synthesis features an epoxide opening reaction, an asymmetric reduction of a β-keto ester, and a cross metathesis strategy for the side chain synthesis.

A new and convenient synthesis of benzo-fused 8-oxabicyclo[3.2.1]octane and 9-oxabicyclo[4.2.1]nonane derivatives are described. The reaction involved a TiCl(4)-mediated tandem carbonyl or imine addition followed by a Friedel-Crafts cyclization to provide these functionalized derivatives in good to excellent yields and high diastereoselectivity.

A stereoselective synthesis of (−)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia–Kocienski olefination.

[structure--see text] An efficient and highly stereoselective synthesis of cryptophycin B (2), a potent cytotoxic agent, is described. The ester-derived titanium-enolate-mediated syn-aldol reaction was employed to generate the stereocenters C(5) and C(6). The route is convergent and provides a convenient access to the synthesis of structural variants of cryptophycin B as well as members of its family.

An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels−Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff−Kishner reduction, Rubottom oxidation, and Suzuki−Miyaura coupling to furnish brevisamide.

The synthesis of a series of stereochemically defined spirocyclic compounds and their use as novel P2-ligands for HIV-1 protease inhibitors are described. The bicyclic core of the ligands was synthesized by an efficient nBu 3SnH-promoted radical cyclization of a 1,6-enyne followed by oxidative cleavage. Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported.

A novel diastereoselective synthesis of substituted pyrrolidines has been developed. Asymmetric multicomponent reactions of optically active phenyldihydrofuran, N-tosyl imino ester, and silane reagents in a one-pot operation afforded highly substituted pyrrolidine derivatives diastereoselectively. The reaction is quite efficient and constructed up to three stereogenic centers in a single operation.

[reaction: see text] General, high-yield tandem electrophilic fluorination and modified Julia olefination for the synthesis of fluoro olefins is reported. A series of alpha-fluoro 1,3-benzothiazol-2-yl sulfone-based synthons were synthesized via deprotonation-fluorination. Of critical importance for high-yield fluorinations were heterogeneous reaction conditions, as under homogeneous conditions only starting sulfones were recovered. The alpha-fluoro 1,3-benzothiazol-2-yl sulfones so obtained were subjected to condensations with a variety of aldehydes and ketones to afford high yields of regiospecifically fluorinated olefins.

[reaction: see text] (-)-Doliculide, a potent antitumor agent, is synthesized stereoselectively in a convergent manner. The key strategy involves a stereoselective synthesis of the polyketide unit and synthesis of the D-tyrosine derivative, followed by assembly of the fragments by an esterification and cycloamidation reaction sequence. The synthesis of the polyketide fragment was achieved by an iterative asymmetric synthesis to install stereoselectively both 1,3-dimethyl groups and the 1,3-diol unit by utilizing asymmetric cyclopropanations and Sharpless asymmetric epoxidations as the key steps.

A stereoselective synthesis of (-)-tetrahydrolipstatin is described. The synthesis involves an asymmetric ester derived titanium enolate anti-aldol reaction, a nitro-aldol reaction to append the C-2' C(11) side chain, and a diastereoselective reduction of a beta-hydroxy ketone to an anti-1,3-diol functionality followed by its elaboration to (-)-tetrahydrolipstatin.

[formula: see text] Platinum and palladium chiral bisphosphine complexes and their counterion effects in asymmetric Diels-Alder reactions have been investigated. The reaction of cyclopentadiene and various bidentate dienophiles in the presence of a catalytic amount of Pt(II)- or Pd(II)-BINAP complex proceeds with excellent endo/exo selectivity as well as endo enantioselectivity (up to 99% ee).