Ru(II)-Catalyzed C-H alkylation of N-Benzyltriflamide with Maleimides: Synthesis of o-Succinimide Substituted Benzaldehydes.

A ruthenium-catalyzed N-benzyltriflamide assisted C-H alkylation with maleimide followed by hydrolysis of in situ generated imine has been developed for the first time. This synthetic method results in the efficient synthesis of o-succinimide derivatives of benzaldehydes. This reaction involves less expensive and mild reaction conditions and shows excellent site selectivity and good functional group compatibility.

Total synthesis of diplofuranone A and diapolic acid A.

The first and concise syntheses of the anticancer agent diplofuranone A and the fatty acid-derived metabolite diapolic acid A have been demonstrated using easily accessible and commercially available starting materials. The key feature of these syntheses is the efficient diversification of highly stereo- and chemoselectively constructed (E,E)-1,6-dioxo-2,4-dienes using ruthenium catalytic conditions, which enabled straightforward access to diversely substituted bioactive molecules.

Asymmetric Ru/Cinchonine Dual Catalysis for the One-Pot Synthesis of Optically Active Phthalides from Benzoic Acids and Acrylates.

Herein, we report the asymmetric Ru/cinchonine dual catalysis that provides straightforward access to enantioselective synthesis of C-3 substituted phthalides via tandem C-H activation/Michael addition cascade. The use of readily accessible and less expensive [RuCl2(p-cym)]2 and cinchonine catalyst for the one-pot assembly of chiral phthalides greatly overcomes the present trend of using highly sophisticated catalysts. The developed method provides access to both enantiomers of a product using pseudoenantiomeric cinchona alkaloids as catalysts streamlining the synthesis of phthalide in both the optically active forms.

Diversification of (E,E)-1,6-Dioxo-2,4-Dienes for the Synthesis of (+)-Aspicillin, Isolaurepan, and ß-Parinaric Acid.

A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product ß-parinaric acid and the total synthesis of non-terpenoid metabolite isolaurepan have been achieved using a ruthenium-catalyzed stereo- and chemoselective oxidative coupling reaction of easily accessible vinyl ketones and acrylates. The crucial transformation involves the efficient synthesis and functionalization of stereodefined (E,E)-1,6-dioxo-2,4-dienes using simple reaction protocols, which enabled straightforward access to a diverse range of bioactive natural products.

Ruthenium-Catalyzed Oxidative Cross-Coupling Reaction of Activated Olefins with Vinyl Boronates for the Synthesis of (E,E)-1,3-Dienes.

An oxidative cross-coupling reaction between activated olefins and vinyl boronate derivatives has been developed for the highly stereoselective construction of synthetically useful (E,E)-1,3-dienes. The highlight of this reaction is that exclusive stereoselectivity (only E,E-isomer) was achieved from a base-free, ligand-free, and mild catalytic condition with a less expensive [RuCl2(p-cymene)]2 catalyst.

Cp*Co(III)-Catalyzed Ketone-Directed ortho-C-H Activation for the Synthesis of Indene Derivatives.

A weakly coordinating, carbonyl-assisted C-H activation of aromatic systems with α,ß-unsaturated ketone and subsequent aldol condensation has been developed using a Cp*Co(CO)I2 catalyst. The developed method is the first example of indene synthesis by cobalt-catalyzed C-H activation. In addition, the reaction requires mild reaction conditions and easily accessible starting materials, and it shows excellent functional group compatibility.

Total Synthesis of (-)-Phomoarcherin C.

A full account on the first total synthesis of a chroman meroterpenoid, (-)-phomoarcherin C, has been described. Key synthetic transformations include phenyl boronic acid-mediated 6π-electrocyclization reaction, a stereospecific hydrogenation driven by thermodynamic conformational stability of the product, and regioselective formylation. The strategy employed is considerably short, is atom-economical, and can open the doors to provide access to various other natural products of the same kind.

Bio-inspired enantioselective total syntheses of (-)-viminalins A, B, H, I, and N and structural reassignment of (-)-viminalin M.

Bio-inspired enantioselective total syntheses of (-)-viminalins A, B, H, I, and N, isolated from the Myrtaceae family, were accomplished in a convergent fashion in 5, 5, 1, 1, and 3 steps, respectively. A highly regio- and diastereoselective oxidative [3 + 2] cycloaddition reaction of acylphloroglucinols with α-phellandrene, diastereoselective modified Friedel-Crafts reaction of acylphloroglucinols with piperetol, and stereoselective epoxidation of extremely hindered ß-face were described as key reactions.

Enantiospecific Total Syntheses of (+)-Hapalindole H and (-)-12-epi-Hapalindole U.

Enantiospecific total syntheses of (+)-hapalindole H and (-)-12-epi-hapalindole U as well as the formal syntheses of (+)-hapalindole Q and (+)-12-epi-fischerindole U isothiocyanate have been described. Key steps of our approach feature expedient, highly regio- and diastereoselective Lewis acid catalyzed Friedel-Crafts reaction of indole with cyclic allylic alcohols and intramolecular reductive Heck reaction. Efficiency of the synthetic route also relies on an alkynyl aluminate complex driven regioselective nucleophilic epoxide opening from a sterically hindered site.

Total Synthesis of Adunctin B.

Total synthesis of (±)-adunctin B, a natural product isolated from Piper aduncum (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization.

Biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D.

The first biomimetic total syntheses of chromane meroterpenoids, guadials B and C, guapsidial A and psiguajadial D have been completed. The key synthetic transformation involves an efficient and high yielding hetero-Diels-Alder reaction. The two structurally isomeric natural products, guadials B and C, were obtained from a common o-quinone methide in the separate reactions with α-pinene and ß-pinene, respectively. The two regioisomeric natural products, guapsidial A and psiguajadial D, were achieved in a single chemical operation.

A Novel Pd-Catalysed Annulation Reaction for the Syntheses of Pyrroloindoles and Pyrroloquinolines.

Pd-catalysed annulation reactions between indole derivatives and internal alkyne esters leading to various pyrrolo[1,2-a]indoles and pyrroloquinolines have been developed. The strategy involves an intermolecular addition of the indole nitrogen on to the internal alkyne ester followed by an intramolecular insertion of a vinyl-palladium complex into the carbonyl group. This method offers a facile and practical approach to pyrrolo[1,2-a]indoles and pyrroloquinolines.

Expedient synthesis of densely substituted pyrrolo[1,2-a]indoles.

Cu(OTf)2 catalyzed [6 + 2] cycloaddition reaction of indolyl-2-carbinols with various dienophiles such as indole derived α,ß-unsaturated esters, ketones, nitriles and cinnamates is described. The strategy was further applied for the synthesis of optically active pyrrolo[1,2-a]indoles in >97% de using the chiral auxiliary based approach.

Enantiospecific total syntheses of meroterpenoids (-)-F1839-I and (-)-corallidictyals B and D.

Enantiospecific total syntheses of spiromeroterpenoid natural products (-)-F1839-I and (-)-corallidictyals B and D were achieved using the environmentally benign and highly atom economical Lewis acid catalysed Friedel-Crafts reaction and a highly regio- and stereoselective spirocyclic C-O bond formation reaction.

Enantiospecific total syntheses and assignment of absolute configuration of cannabinol-skeletal carbazole alkaloids murrayamines-O and -P.

First enantiospecific total syntheses of the cannabinol-skeletal carbazole alkaloids murrayamines-O and -P isolated from root barks of Murraya euchrestifoli, have been accomplished by highly diastereoselective, Lewis acid catalyzed coupling reactions of commercially available monoterpenes with carbazole derivative, which in addition to confirming the structure also established the absolute configuration of the natural products. Synthesis of both natural products and their enantiomers was achieved with high atom economy, in a protecting-group free manner and in six steps longest linear sequence from commercially available aniline derivative and verbenol.

Enantioselective total syntheses of (+)-hostmanin A, (-)-linderol A, (+)-methyllinderatin and structural reassignment of adunctin E.

A one-step protocol has been developed for the enantioselective synthesis of hexahydrodibenzofuran derivatives using a modified Friedel-Crafts reaction. The developed method was applied to the synthesis of a series of natural products including (+)-hostmanin A, (+)-methyllinderatin, and (-)-linderol A. The synthetic and spectroscopic data investigations led to the structural reassignment of natural product adunctin E, which was further confirmed by single-crystal X-ray analysis.

FeCl3-Catalyzed Intramolecular Michael Reaction of Styrenes for the Synthesis of Highly Substituted Indenes.

An intramolecular FeCl3-catalyzed Michael addition reaction of styrene, a poor nucleophile, onto α,ß-unsaturated ketones was developed for the synthesis of highly substituted indene derivatives. The method was further applied to the total synthesis of the sesquiterpene natural products (±)-jungianol and 1-epi-jungianol.

Asymmetric Total Synthesis of (+)-Verrubenzospirolactone and (+)-Capillobenzopyranol.

The first asymmetric total synthesis of (+)-verrubenzospirolactone (1), a distinctive highly fused benzosesquiterpenoid, characterized by a pentacyclic skeletal structure, is realized through a concise 10-step synthetic pathway with an impressive 22.8% overall yield. Notable highlights of this synthetic endeavor include (i) the introduction of a Ru-catalyzed ortho C-H activation step, (ii) the application of Pd-catalyzed asymmetric allylic alkylation to establish a pivotal stereocenter at C-3 with an excellent enantiomeric excess, (iii) B-alkyl Suzuki-Miyaura coupling to construct a Diels-Alder precursor, and, ultimately, (iv) the successful deployment of an intramolecular Diels-Alder reaction to complete the synthesis of (+)-verrubenzospirolactone without erosion of the enantiomeric excess.

Ru(II)-Catalyzed Deoxygenative Formal [3 + 1 + 2] Benzannulation of Allyl Alcohols and Acetylenediesters via C-H Activation and Selective Carbon-Carbon Triple Bond Cleavage.

An unprecedented Ru(II)-catalyzed deoxygenative, site-selective formal [3 + 1 + 2] benzannulation reaction for the efficient synthesis of highly substituted benzene molecules is reported. This reaction between allyl alcohols and acetylenedicarboxylate esters proceeds via cascade C-H activation, consecutive double migratory insertion with alkynes, and cycloaromatization followed by an unusual specific C-C triple bond cleavage.

Enantioselective total synthesis of atisane diterpenoids: (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one.

Enantioselective total synthesis of (+)-sapinsigin H, (+)-agallochaol C, and (+)-16α, 17-dihydroxy-atisan-3-one has been accomplished starting from enantiopure Wieland-Miescher ketone. Key features of the syntheses include a benzannulation step to construct the tricyclic core, an oxidative dearomatization step to generate the diene, and a Diels-Alder reaction with ethylene gas to establish the bicyclo[2.2.2]octane framework. Efficient late-stage functionalisation of the A-ring by aerobic oxidation and Baeyer-Villiger oxidation completed the atisane target molecules.