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Research has been conducted on the preparation of the conformationally restricted nicotinoid from D- and L-glutamic acid. The pyroglutamic acid derivative coupling with ortho-lithiated 4-chloropyridine is described.

1,3,5-Triazinanes, as a kind of versatile building block, are applied in the synthesis of chromeno[2,3- d ]pyrimidin-5-one derivatives via two different reaction modes, which perfectly exhibits the powerful function of 1,3,5-triazinane as a three-atom synthon along with the structure variation of another substrate. The two annulation reactions proceed under mild conditions and bear broad substrate scope and high yield.

A microwave-promoted multicomponent reaction of 3-formylchromones, amines, and paraformaldehyde was achieved under catalyst-free and solvent-free conditions, delivering 5 H -chromeno[2,3- d ]pyrimidin-5-one derivatives in good to excellent yields via an unexpected annulation pathway, which further expanded the synthetic application of paraformaldehyde as a C1 building block.

We have developed cobalt-catalyzed, bidentate 2-(1-methylhydrazinyl)pyridine (MHP)-directed C( sp 2 )-H alkylation/annulation of benzoic hydrazides with various alkenes. Notably, diverse cyclopenta[ c ]isoquinolinones and dihydroisoquinolinones were obtained via this functional group-tolerant protocol. The reaction can be performed on a gram scale while maintaining an excellent yield, and the directing group can be removed efficiently under mild conditions. Furthermore, density-functional theory (DFT) calculations provide an incisive understanding of the observed regioselectivities for different olefins.

The regioselective functionalization reaction of unprotected carbazoles with donor-acceptor (D-A) cyclopropanes has been demonstrated for the first time. With Sc(OTf) 3 as Lewis acid catalyst, the N-H functionalization of carbazoles takes place through a highly selective nitrogen-initiated nucleophilic ring opening reaction. Significantly, by engaging TfOH as Brønsted acid catalyst, a straightforward C-H functionalization at the 3-position of the unprotected carbazole proceeds via Friedel-Crafts-type addition. This strategy facilitates the diversity-oriented synthesis of carbazole-containing heterocycles and expands the novel application of D-A cyclopropanes.

The synthesis of 3,4-dihydro-2 H -1,3-thiazines from α-enolic dithioesters and 1,3,5-triazinanes has been achieved via a formal (3 + 3) annulation reaction under thermal conditions, where 1,3,5-triazinanes were utilized as three-atom synthons. This transformation is catalyst-free and additive-free.

Pyridinium 1,4-zwitterionic thiolates, as a novel kind of sulfur-containing synthon, have been applied to the synthesis of 12a H -benzo[ f ]pyrido[1,2- d ][1,4]thiazepines and benzo[ b ]thiophenes. Benzopyridothiazepines were produced through a 1,5-dipolar cycloaddition reaction from pyridinium 1,4-zwitterionic thiolates with arynes, whereas benzothiophenes as side products were generated via a [3 + 2] cascade cyclization reaction. The [5 + 2] reaction mode of pyridinium 1,4-zwitterionic thiolates is disclosed for the first time.

An efficient DABCO-catalyzed three-component formal [3 + 2 + 1] annulation, involving a Morita-Baylis-Hillman carbonate, a 1,3-ketoester, and a primary amine, leading to one-pot synthesis of substituted 4-aryl-1,2,3,4-tetrahydropyridines, has been developed. The densely functionalized products were generally obtained in good to excellent yields under mild conditions. The structures including the relative stereoconfigurations of the representative products were confirmed by X-ray diffraction analysis.

A chemoselective N-arylation reaction of 2-aminopyridine derivatives with arynes in good to excellent yields has been described. The N-arylation products could be further applied to the facile construction of benzoisoquinuclidines and isoquinuclidines as well as pyrido[1,2-a]benzimidazoles.

An efficient protocol for facile construction of spiro[indazole-3,3'-indolin]-2'-ones was developed via [3 + 2] dipolar cycloaddition of arynes with 3-diazoindolin-2-ones under mild conditions in excellent yields. Subsequent thermal isomerization of the spiro[indazole-3,3'-indolin]-2'-ones readily afforded indazolo[2,3-c]quinazolin-6(5H)-ones.

The first total syntheses of (+)-villatamines A and B have been realized in six and five steps, respectively. The stereogenic center present in these two naturally occurring alkaloids should have an (S)-configuration based on our results.

(+)-Mintlactone, a bicyclic monoterpene natural product, has been efficiently assembled from (-)-citronellol in three steps. The synthesis features nitrous acid-induced formal isopropylidene "demethanation" and the molybdenum-mediated intramolecular hetero-Pauson-Khand reaction.

An efficient approach to synthesize naphtho[1,2-b]furan has been developed via platinum-catalyzed tandem reaction. This new tandem catalysis induces a cycloisomerization of allenyl ketone, followed by a 6pi-electrocyclization-type reaction of carbene intermediate. The metal carbene proved to be an effective intermediate in the 6pi-electrocyclization-type reaction.

An asymmetric total synthesis of (-)-5,6-dihydrocineromycin B has been accomplished in 13 steps from (-)-linalool O-triethylsilyl ether or 12 steps from geraniol. The present synthesis features (i) an intermolecular Wittig reaction involving an aldehyde possessing a ketophosphonate functionality and (ii) an intramolecular Horner-Wadsworth-Emmons olefination.

(+)-pyrido[3,4- b]homotropane (PHT) was efficiently constructed in 12 steps from N, N-diisopropylisonicotinamide. The synthesis features (i) RCM reaction in installing the homotropane skeleton, (ii) Snieckus ortho-lithiation of N, N-diisopropylisonicotinamide followed by acylation, (iii) Myer reduction of bulky tertiary amide to alcohol with LiBH 3NH 2, and (iv) utilization of L-glutamic acid to introduce and establish the requisite stereogenic centers.

The first total synthesis of (+/-)-subincanadine F, a bioactive indole alkaloid structurally featuring a 1-azabicyclo[4.3.1]decane unit, has been realized from 1-(para-methoxybenzyl)tryptamine in six steps. The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by a SmI2-mediated ring opening followed by an acid-mediated Mannich reaction. In addition, the tetracyclic ketoester 6, a key intermediate potentially useful for synthesizing structurally related indole alkaloids as well, was obtained in one step from alpha,beta-diketoester 5.

We have described a concise construction of the pentacyclic benz[f]indolo[2,3-a]quinolizidine intermediate 3 (with an overall yield of 54% for three steps), featuring a tandem intermolecular formal aza-[3 + 3] cycloaddition/Pictet-Spengler cyclization. The present work can be considered as a formal synthesis of beta-carboline alkaloid (+/-)-tangutorine. Our strategy disclosed herein constitutes a new effective general synthetic approach toward the indoloquinolizidine family of alkaloids.

8O-methylaphanorphine was synthesized from 4-methoxyphenylacetaldehyde in 36% overall yield and in nine steps, featuring the formation of ring B via a Friedel-Crafts alkylative cyclization with the concomitant stereospecific introduction of the benzylic quaternary carbon center. The current work constitutes an efficient enantioselective formal synthesis of 3-benzazepine marine alkaloid (-)-aphanorphine.