Synthesis of precisely functionalizable curved nanographenes via graphitization-induced regioselective chlorination in a mechanochemical Scholl Reaction.

While the synthesis of nanographenes has advanced greatly in the past few years, development of their atomically precise functionalization strategies remains rare. The ability to modify the carbon scaffold translates to controlling, adjusting, and adapting molecular properties. Towards this end, here, we show that mechanochemistry is capable of transforming graphitization precursors directly into chlorinated curved nanographenes through a Scholl reaction. The halogenation occurs in a regioselective, high-yielding, and general manner. Density Functional Theory (DFT) calculations suggest that graphitization activates specific edge-positions for chlorination. The chlorine atoms allow for precise chemical modification of the nanographenes through a Suzuki or a nucleophilic aromatic substitution reaction. The edge modification enables modulation of material properties. Among the molecules prepared, corannulene-coronene hybrids and laterally fully π-extended helicenes, heptabenzo[5]superhelicenes, are particularly noteworthy.

Interrupting Nazarov Reaction with Different Trapping Modality: Utilizing Potassium Alkynyltrifluoroborate as a σ-Nucleophile.

The putative oxyallyl cation intermediate generated following Nazarov cyclization of dienone has been successfully intercepted with potassium alkynyltrifluoroborates which act as σ-nucleophiles in the presence of BF3·Et2O. This new trapping modality allowed unprecedented introduction of an alkynyl moiety to the cyclopentanone framework by means of an interrupted Nazarov reaction. The α-alkynyl cyclopentanone product can be further transformed into an array of densely functionalized cyclic compounds.

The first intermolecular interrupted imino-Nazarov reaction: expeditious access to carbocyclic nucleoside analogues.

The analogous imino-variant of the Nazarov reaction suffers from unfavorable energetics associated with the ring closure process, thereby limiting the utility of this class of reactions. In this report, the realization of the first intermolecular interrupted imino-Nazarov reaction utilizing silylated pyrimidine derivatives as nucleophilic trapping partners culminated in an expedient synthetic route to carbocyclic nucleoside analogues. The potential application of silylated nucleobases to intercept the oxyallyl cation in other variants of the Nazarov reaction provides vast opportunities to develop new strategies for the formation of carbocyclic nucleoside analogues.

A concise route to the highly-functionalized azetidine precursor: the enantioselective synthesis of penaresidin B.

An efficient and high-yielding synthesis of penaresidin B is disclosed herein. The concise 8-step synthesis of azetidine aldehyde was devised by incorporating our novel strategy for ready access to 3-amino-2,3-dideoxysugars via regio- and stereoselective tandem hydroamination/glycosylation of glycal as the key step.

Interrupted imino-Nazarov cyclization of 1-aminopentadienyl cation and related cascade process.

Facile 4π conrotatory imino-Nazarov cyclization of a 1-aminopentadienyl cation generated from condensation an aldehyde and secondary aniline in the presence of a catalytic amount of a Lewis acid has been developed. Silver(I)-catalyzed intramolecular arene trapping of the resulting cyclic oxyallyl cation leads to formation of tricyclic indoline-fused cyclopentanone. The use of lanthanide salts allows transformation after the initial trapping to afford tetrahydroquinoline-fused cyclopentenone in a concise manner.

Design and synthesis of multivalent neoglycoconjugates by click conjugations.

A highly stereoselective BF3∙OEt2-promoted tandem hydroamination/glycosylation on glycal scaffolds has been developed to form propargyl 3-tosylamino-2,3-dideoxysugars in a one-pot manner. Subsequent construction of multivalent 3-tosylamino-2,3-dideoxyneoglycoconjugates with potential biochemical applications was presented herein involving click conjugations as the key reaction step. The copper-catalyzed regioselective click reaction was tremendously accelerated with assistance of microwave irradiation.

Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their antiproliferation activities.

A collective synthesis of 4-hydroxy-2-pyridone alkaloids--specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C--has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 µM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.

Directed orthometalation and the asymmetric total synthesis of N-deoxymilitarinone A and torrubiellone B.

A diverted total synthesis (DTS) approach to the total synthesis of pyridone alkaloids N-deoxymilitarinone A (8) and torrubiellone B (10) has been developed. The common intermediate 14 was first assembled by a dual directed orthometalation process using a methoxymethyl group as directed metalation group. Other crucial steps include the assembly of polyenes under aldol condensation for DTS using general and concise strategy and diastereoselective synthesis of the syn-dimethyl array by an Evans aldol reaction.

Ferrier-type N-glycosylation: synthesis of N-glycosides of enone sugars.

A mild and efficient protocol for the stereoselective synthesis of N-glycosides of enone sugars has been developed. The reaction proceeds to provide N-glycosides of enone sugars in moderate to good yields with preferential α-anomeric selectivity. Additionally, applications of the N-glycosides of enone sugar derivatives as precursor to assemble some biochemically functional derivatives have also been explored. This includes the use of N-glycosides of enone sugars as reactive dienophile in asymmetric synthesis of bicyclic adduct through Diels-Alder cycloaddition reaction.

Triflimide-catalyzed allyl-allyl cross-coupling: a metal-free allylic alkylation.

A highly efficient metal-free intermolecular C(sp3)-C(sp3) allyl-allyl cross-coupling protocol between allyl acetates and allyltrimethylsilanes, which proceeded smoothly in the presence of catalytic triflimide to form 1,5-dienes with good to excellent regioselectivity, has been developed.

Direct and stereoselective synthesis of 1,3-cis-3- arylsulphonaminodeoxydisaccharides and oligosaccharides.

The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each component.

Ready access to 3-amino-2,3-dideoxysugars via regio- and stereo-selective tandem hydroamination-glycosylation of glycals.

A highly stereoselective BF(3)·OEt(2)-promoted tandem hydroamination-glycosylation on a glycal scaffold has been developed to form 3-amino-2,3-dideoxysugars in a one-pot procedure. This efficient multicomponent reaction protocol offers simplicity and general applicability to a broad range of variations on each component.

A short and highly efficient synthesis of L-ristosamine and L-epi-daunosamine glycosides.

A highly efficient synthesis of L-ristosamine and L-epi-daunosamine glycosides via BF(3)·OEt(2) promoted tandem hydroamination/glycosylation of 3,4-di-O-acetyl-6-deoxy-L-glucal and L-galactal has been developed. The new method proceeds in a completely stereocontrolled manner within a short reaction time. Preparation of a library of L-ristosamine and L-epi-daunosamine glycosides with potential biochemical applications, by varying each component, exemplified the generality of the reaction.