Synthesis of the Tetrasaccharide Glycone Part of Tetrocarcin A.

A de novo synthesis of the tetrasaccharide fragment of tetrocarcin A is described. The key feature of this approach is highlighted by the regio- and diastereoselective Pd-catalyzed hydroalkoxylation of ene-alkoxyallenes with an unprotected l-digitoxose glycoside. The subsequent reaction with digitoxal in combination with chemoselective hydrogenation generated the target molecule.

Sequential Metal Catalysis towards 7-Oxostaurosporine and Its Non-Natural Septanose Analogue.

We report sequential metal catalysis towards indolocarbazole glycosides. The signature event is highlighted by i) Pd0 -catalyzed addition of indolocarbazole to alkoxyallene combined with ring-closing-metathesis; ii) Ru-catalyzed chemoselective olefin migration; iii) PdII -catalyzed oxidative cyclization to build the bicyclic core structure of the target compounds. This approach gave access to both natural pyranose- and non-natural septanose glycosides. A short formal synthesis of 7-oxostaurosporine was achieved via this strategy.

Generation of N-H Imines from α-Azidocarboxylic Acids through Ru-Catalyzed Decarboxylation.

A new method for the synthesis of N-H imines from α-azidocarboxylic acids was developed, which proceeds through decarboxylative C-C bond cleavage catalyzed by a commercial diruthenium complex ([CpRu(CO)2]2) under visible light irradiation at room temperature within several minutes. The reactive products undergo condensation, which forms cyclic trimers (2,4,6-trialkylhexahydro-1,3,5-triazines) or linear N,N'-bis(arylmethylidene)arylmethanediamines in quantitative yields. Alternatively, the N-H imines can be trapped with benzylamine and 2-(aminomethyl)aniline, providing stable N-benylimines and tetrahydroquinazolines, respectively. Subsequent oxidation of tetrahydroquinazolines produced quinazolines.

Palladium-Catalyzed Asymmetric Decarboxylative Addition of ß-Keto Acids to Heteroatom-Substituted Allenes.

The Pd-catalyzed asymmetric addition reaction of ß-keto acids to heteroatom-substituted allene is reported. This reaction generates ß-substituted ketones in an asymmetric manner through a branch-selective decarboxylative allylation pathway. The reaction accommodates various alkoxyallenes as well as amidoallenes.

Flexible Total Synthesis of 11-Deoxylandomycins and Their Non-Natural Analogues by Way of Asymmetric Metal Catalysis.

A de novo first collective total synthesis of 11-deoxylandomycins is reported. A signature step is featured by the Pd-catalyzed asymmetric addition of alcohol to ene-alkoxyallenes that assembles oligomeric 2,3,6-trideoxyoligosaccharides. The unique feature of the protocol is illustrated by a flexible access to various natural 11-deoxylandomycins as well as non-natural analogues.

Synthesis of Deoxyaminosugar Cyclohexyl-l-callipeltose and Its Diastereomer Using Pd-Catalyzed Asymmetric Hydroalkoxylation.

Cyclohexyl-l-callipeltose, an aminodeoxysugar subunit of Callipeltoside A, was synthesized in six steps and 40% overall yield from readily available (S)-4-methylpent-4-en-2-ol and cyclohexyloxyallene. The signature step is represented by Pd-catalyzed asymmetric intermolecular hydroalkoxylation that generates the key dihydropyran intermediate upon combination with the ring-closing metathesis reaction. Notably, an unnatural diastereomer of the target compound could also be obtained with comparable efficiency simply by using the enantiomeric ligand.

A Convergent Synthetic Strategy towards Oligosaccharides containing 2,3,6-Trideoxypyranoglycosides.

A de novo synthetic strategy for the production of oligosaccharides containing 2,3,6-trideoxypyranoglycoside is reported. The key event is the Pd-catalyzed asymmetric diastereoselective hydroalkoxylation of ene-alkoxyallene-linked glycosidic fragments. The utility of this approach was demonstrated by the activation-free, stereodivergent, and convergent synthesis of various 2-deoxyoligosaccharides, as well as their aglycon conjugates.

Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide C via Convergent Fragment Coupling Using a Tertiary Carbon Radical.

The development of a convergent fragment coupling strategy for the enantioselective total syntheses of a group of rearranged spongian diterpenoids that harbor the cis-2,8-dioxabicyclo[3.3.0]octan-3-one unit is described. The key bond disconnection relies on a late-stage fragment coupling between a tertiary carbon radical and an electron-deficient alkene to unite two ring systems and form two new stereocenters, one of which is quaternary, in a stereoselective and efficient manner. This strategy is applied toward scalable 14-15 step syntheses of three rearranged spongian diterpenoids, cheloviolenes A and B, and dendrillolide C.

Versatile Construction of 6-Substituted cis-2,8-Dioxabicyclo[3.3.0]octan-3-ones: Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide C.

A short enantioselective synthesis of 6-substituted cis-2,8-dioxabicyclo[3.3.0]octan-3-ones is described. The pivotal step is coupling of a tertiary radical generated directly from a tertiary alcohol with a 3-chloro-5-alkoxybutenolide. This strategy is applied toward scalable 14-15 step syntheses of three rearranged spongian diterpenoids: cheloviolenes A and B and dendrillolide C.

Redox reaction between benzyl azides and aryl azides: concerted synthesis of aryl nitriles and anilines.

A unique and novel reaction between benzyl azides and aryl azides is described to synthesize aryl nitriles and anilines concurrently, which is catalyzed with a photoactivated diruthenium complex. N-Unsubstituted imines (N-H imines) are generated first from benzyl azides, followed by the hydrogen transfer reaction between N-H imines and aryl azides. A wide range of aryl nitriles and anilines were synthesized under neutral and mild reaction conditions.

De Novo Synthesis of Furanose Sugars: Catalytic Asymmetric Synthesis of Apiose and Apiose-Containing Oligosaccharides.

A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium-catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring-closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose-containing disaccharides and a unique convergent synthesis of trisaccharides.

Pd-catalyzed asymmetric intermolecular hydroalkoxylation of allene: an entry to cyclic acetals with activating group-free and flexible anomeric control.

A ligand-directed metal-catalyzed asymmetric intermolecular hydroalkoxylation of alkoxyallene is reported. Combined with ring-closing-metathesis, this reaction offers a new atom-efficient synthetic method toward various cyclic acetals with elaborate anomeric control. Synthetic utility of the reaction was demonstrated by the atom-efficient and stereodivergent access to various mono- and disaccharides.

Access to trans-3,4-dihydroxy-2-alkylpyrrolidines and piperidines by use of stereodefined cyclic N,O-acetals as a diversity-generating element.

A highly efficient and stereoselective synthetic pathway towards trans-3,4-dihydroxy-2-alkylpyrrolidines and piperidines is described. The nature of the protecting groups on the hydroxyl moieties played a crucial role on the trans selectivity. By using this method, a concise total synthesis of (-)-2-epilentiginosine has been achieved.

Novel catalyst system for hydrostannation of alkynes.

A catalyst system was developed for the highly regio- and stereoselective hydrostannation of a range of alkynes with tributylstannane under mild conditions. The active catalytic species was generated from a stable diruthenium complex by illuminating household fluorescent light (30 W) at room temperature.

Synthesis of the tricyclic core in stemonamine alkaloids via one-pot gold(I)-catalyzed cyclization and schmidt rearrangement: formal synthesis of (±)-stemonamine.

An efficient synthesis of the tricyclic cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus of stemonamine alkaloids is reported. The key reaction utilizes a one-pot gold(I)-catalyzed cyclization and SnCl4-mediated Schmidt rearrangement. Notably, the phosphine ligand had a crucial effect on the gold(I)-catalyzed cyclization. As an application of this new methodology, the formal synthesis of (±)-stemonamine has been accomplished.

C-H activation guided by aromatic N-H ketimines: synthesis of functionalized isoquinolines using benzyl azides and alkynes.

Aromatic N-H ketimines were in situ generated from various benzylic azides by ruthenium catalysis for the subsequent Rh-catalyzed annulation reaction with alkynes to give the corresponding isoquinolines. In contrast to conventional synthetic methods for aromatic N-H ketimines, our protocol works under mild and neutral conditions, which enabled the synthesis of isoquinolines having various functionalities such as carbonyl, ester, alkenyl, and ether groups. In addition, the imidates generated from α-azido ethers were successfully used for the synthesis of 1-alkoxyisoquinolines.

Coherent and homogeneous intramolecular charge-transfer dynamics of 1-tert-butyl-6-cyano-1,2,3,4-tetrahydroquinoline (NTC6), a rigid analogue of DMABN.

We report the intramolecular charge-transfer (ICT) dynamics of 1-tert-butyl-6-cyano-1,2,3,4-tetrahydroquinoline (NTC6), a planar analogue of 4-(dimethylamino)benzonitrile (DMABN), by using time-resolved fluorescence (TRF) and TRF spectra (TRFS). TRFS allow accurate determination of the ICT dynamics free from the spectral relaxation caused by the solvation and vibronic relaxation. For NTC6 in tetrahydrofuran (THF), the locally excited (LE) state is populated exclusively presumably via a conical intersection from the initial photoexcited S2 (La) state, and the LE state undergoes ICT single exponentially with a time constant of 1.8 ± 0.2 ps. In acetonitrile, however, both LE (22%) and ICT (78%) states are populated from the S2 state, and the population in the LE state undergoes ICT in 800 ± 100 fs. The ICT state undergoes further relaxation in 1.2 ps along the solvation and the intramolecular nuclear coordinates involving the rotation of the amino group to form a twisted ICT state. Coherent nuclear wave packet motions of 130 cm(-1), which can be assigned to the -C≡N group bending mode, were observed in the TRF of the reactant (LE) and product (ICT) states, indicating that the ICT reaction is partially coherent. Compared with DMABN, the ICT dynamics of NTC6 are quite homogeneous, and we speculated on the narrow conformational distribution of NTC6 in the ground state along the rotation of the amino group due to its rigid structure.

Total Synthesis of the Purported Structure of Branched Resin Glycosides Merremoside G and H2.

The first total synthesis of the purported structure of branched resin glycosides merremoside G and H2 is accomplished. A signature step is represented by the sequential transition-metal-catalyzed coupling of stable trisaccharide homoallylic alcohol and monosaccharide alkoxyallene to afford the pentasaccharide skeleton. This de novo strategy is conducted under mild conditions with no need of preactivation. In addition, it allows for efficient preparation of the target compounds in combination with late-stage functionalization.

Formal Synthesis of (+)-Sinefungin by Way of Sequential Asymmetric Metal Catalysis.

Here, we report a de novo approach toward (+)-sinefungin, a potent inhibitor of the physiological methyl transfer process. A key feature is represented by the sequential metal catalysis combining Pd-catalyzed hydroalkoxylation and ring-rearrangement metathesis. The unique advantage of the method is highlighted by the unprecedented complete control of the C6 stereocenter.

Stereodefined N,O-acetals: Pd-catalyzed synthesis from homopropargylic amines and utility in the flexible synthesis of 2,6-substituted piperidines.

We developed a conceptually new synthetic strategy which exploits the stereochemical information of labile acyclic N,O-acetals. The key to this strategy, chemo- and stereoselective synthesis of N,O-acetals, was achieved by the Pd-catalyzed addition of sulfonyl-protected homopropargylic amines to alkoxyallene. The N,O-acetals generated in this way were combined with Au-catalyzed cycloisomerization to give an access to 2,6-disubstituted piperidines with stereochemical flexibility.