Reductive Oxy-Nazarov Cyclization toward Expedient Construction of a Cyclopenta[1,2-b]pyrrolo[1,2-a]azepine Ring System: Formal Total Syntheses of Stemonamine and Cephalotaxine.

Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2-b]pyrrolo[1,2-a]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.

Diastereodivergent Synthesis of Pentacyclic Spiroindolines via a Magnesium(II)-Catalyzed Cascade Reaction of N,N'-Cyclic Azomethine Imines with Indolyl-Substituted Isocyanides.

Magnesium(II)-catalyzed cascade reactions of N,N'-cyclic azomethine imines with indolyl-substituted isocyanides are reported herein. The method exhibited a high functional group tolerance and broad substrate scope. A series of anti-pentacyclic spiroindolines containing N,N'-fused heterocycle skeletons were obtained in up to 82% yield with 8.5:1 dr under mild reaction conditions. Intriguingly, a sequential HOAc-mediated protonation results in a diastereoenriched epimerization, which gives rise to the syn-pentacyclic spiroindolines as the sole isomers.

A stereospecific total synthesis of DL-hexahydroapoerysopine.

A stereospecific total synthesis of DL-hexahydroapoerysopine, an intriguing and historically important Apo rearrangement product of the aromatic Erythrina alkaloids bearing the all-cis ring fusion stereochemistry, was achieved via an efficient acid-mediated stereospecific skeletal rearrangement.

Synthesis of polycyclic spiroindolines via the cascade reaction of 3-(2-isocyanoethyl)indoles.

Tandem reactions of the yttrium(iii) catalyzed ring-opening reaction of 2,2'-diester aziridines with 3-(2-isocyanoethyl)indoles and the subsequent Friedel-Crafts/Mannich/desulfonylation were reported. A series of polycyclic spiroindolines containing tetrahydro-ß-carbolines were obtained in moderate to excellent yields (56-92%) in one step under mild reaction conditions. A possible catalytic mechanism was also proposed.

Self-Assembled Two-Dimensional NiO/CeO2 Heterostructure Rich in Oxygen Vacancies as Efficient Bifunctional Electrocatalyst for Alkaline Hydrogen Evolution and Oxygen Evolution.

The development of high-efficiency bifunctional electrocatalysts toward the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline surroundings is essential and challenging for the large-scale generation of clean hydrogen. Herein, a novel self-assembled two-dimensional (2 D) NiO/CeO2 heterostructure (HS) consisting of NiO and CeO2 nanocrystals is prepared through a facile two-step approach, and utilized as an enhanced bifunctional electrocatalyst for the HER and OER under alkaline conditions. It is concluded that this 2 D NiO/CeO2 HS, rich in oxygen vacancies, demonstrates attractive electrocatalytic properties for both the HER and OER in 1 m KOH, including low onset overpotential (η1 ), η10 and Tafel slope, excellent durability, as well as large active surface area. Therefore, the self-assembled 2 D NiO/CeO2 HS is believed to be an efficient bifunctional electrocatalyst toward the HER and OER.

Asymmetric Synthesis of the DEFG Rings of Solanoeclepin A.

Starting from ( R)-seudenol, an asymmetric synthesis of the DEFG rings of solanoeclepin A has been developed. The key transformations include the substrate-controlled asymmetric Staudinger ketene cycloaddition and the intramolecular aldol reaction leading to the tricyclo[5.2.1.01,6]decane core of solanoeclepin A in 10 steps in the longest reaction sequence.

Intramolecular [2 + 2] Cycloadditions of Alkyl(phenylthio)ketenes: Total Synthesis of (+)-Sphaerodiol.

Asymmetric total synthesis of (+)-sphaerodiol (2) has been achieved. A key step is an intramolecular [2 + 2] cycloaddition of alkyl(phenylthio)ketene for rapid assembly of the decalin ring.

Asymmetric Formal Synthesis of (-)-Cephalotaxine via Palladium-Catalyzed Enantioselective Tsuji Allylation.

Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction of the aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor was prepared from Hanaoka's ketone intermediate, which was formed by a novel formic acid promoted ring-expansion reaction.

Diastereoselective Synthesis of Cephalotaxus Esters via Asymmetric Mukaiyama Aldol Reaction.

We report a protocol for efficient stereoselective installation of the chiral oxygen-containing tetrasubstituted tertiary carbon stereocenter of the side chain of cephalotaxus esters by means of highly diastereoselective Mukaiyama aldol reactions between α-keto esters (2) and a (Z)-α-chloro ketene silyl acetal. This protocol permitted synthesis of cephalotaxus esters including six natural products in good to excellent yields (up to 94%) with high diastereoselectivities (dr up to 97:3) and could be performed on a multigram scale.

Total synthesis of (+)-iresin.

The first asymmetric total synthesis of (+)-iresin (4), an historically important ent-Drimane sesquiterpene lactone, was realized from aldehyde 3 via cyclic orthoester 6 in 5 steps. Notable transformations in this synthesis include a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer-Villiger oxidation-olefin epoxidation-epoxy ester cyclization, regioselective Burgess dehydration, and regioselective Fétizon oxidative lactonization.

Formal homoiodo allylsilane annulations: dual total syntheses of (±)-hirsutene and (±)-capnellene.

Dual total syntheses of (±)-hirsutene and (±)-capnellene, two typical linear triquinane sesquiterpenes, were achieved via a formal [3 + 2] annulation strategy, as illustrated schematically. Cyclic homoiodo allylsilanes were employed as key bifunctional synthons in the synthesis, which were readily prepared from the corresponding cyclopropanated cyclopentenones. A formal [3 + 3] annulation approach for the elaboration of the bicyclic framework of the Eudesmane sesquiterpenoids based on this type of synthon was also developed.

Transannular reductive rearrangement of α-amino ketones: construction of aza-tricyclic frameworks of several alkaloids.

Transannular reductive rearrangement of bridged cyclic α-amino ketones led to the aza-tricyclic frameworks azepinoindole, hydrolulolidine, and hydrojulolidine of the typical alkaloids of Stemona, Aspidosperma, and Lycopodium, respectively. This facile approach demonstrates the potential applicability of the Clemmensen-Clemo-Prelog-Leonard reductive rearrangement of tricyclic α-amino ketones for the aza-heterocycle synthesis.

A convergent and stereocontrolled cycloaddition strategy toward eudesmane sesquiterpenoid: total synthesis of (±)-6ß,14-epoxyeudesm-4(15)-en-1ß-ol.

We present in this report the development of a convergent and highly stereocontrolled cycloaddition strategy toward the synthesis of C-1, C-6, and C-14 tris-oxygenated eudesmane sesquiterpenoids. This approach was demonstrated in the first total synthesis of (±)-6ß,14-epoxyeudesm-4(15)-en-1ß-ol (1), a structurally unique ethereal eudesmane sesquiterpenoid, via an effective Diels-Alder construction of a compact functionalized tricycle intermediate from readily available N-benzylfurfurylamine (2) and homoprenyl maleic anhydride (3) as the C(5) and C(10) building blocks, respectively.

Concise total synthesis of (±)-cephalotaxine via a transannulation strategy: development of a facile reductive oxy-Nazarov cyclization.

A concise total synthesis of (±)-cephalotaxine (1) has been achieved from dioxolanone derivative 15 via a transannulation strategy. The key transformation is a facile reductive oxy-Nazarov cyclization as illustrated above, involving presumably a tethered 1,2-oxidopentadienyl cation species 7a or 7b, which represents a new variant of the oxy-Nazarov cyclization and constitutes an effective, regio- and stereospecific 5-hydroxy cyclopentenone annulation protocol under mild hydride reduction conditions.

Formal total synthesis of (±)-estrone via the furano diene approach.

We present in this report the development and realization of a novel formal total synthesis of estrone (1) via the Torgov diene (24) by the furano diene approach, first attempted by Woodward in 1937. The core ring structure 16 was established by an acid-mediated regioselective and stereospecific cyclization of the endo-oxabicyclo[2.2.1]heptene derivative 14, which is readily available from the AlCl(3)-catalyzed Diels-Alder cycloaddition of 2-(3-methoxyphenethyl)furan (4) and dimethyl maleate. The mechanistic pathway of this S(N)' type cyclization is discussed, and the earlier perspectives in our preliminary report (Org. Lett. 2004, 6, 1333) are corrected.

A facile total synthesis of hainanensine via an unusual rearrangement--annulation cascade.

A facile total synthesis of hainanensine (1), a structurally unique Cephalotaxus alkaloid, via an effective acid-mediated rearrangement/Friedel-Crafts annulation cascade (7a/7b --> 8a/8b), is described.

Novel formal synthesis of cephalotaxine via a facile Friedel-Crafts cyclization.

[structure: see text]. A novel formal synthesis of cephalotaxine (CET), the parent structure of the antileukemia Cephalotaxus alkaloids, was achieved via a facile Friedel-Crafts cyclization of the amino (or amido) spiro-cyclopentenone precursor (A) mediated by a protic acid leading to tetracyclic ketone B. A remarkable stereoelectronic effect of the methylenedioxy substituent (R) and an interesting skeletal isomerization of the CET core ring system (B, X = H2) were observed.

A short synthesis of 10-hydroxy 7-spirocyclopropanated camphor.

[Chemical reaction: see text] A short alternative synthesis of the title 10-hydroxy 7-spirocyclopropanated camphor (4) en route to 10-hydroxycamphor (5) was achieved from cyclopentadiene-derived 4-benzyloxymethylspiro[2.4]hepta-4,6-diene (6a) by a facile regioselective Diels-Alder cycloaddition with 2-chloroacrylonitrile in an overall yield of 20%.

A novel stereocontrolled approach to eudesmanolides: total synthesis of (+/-)-gallicadiol and (+/-)-isogallicadiol.

[reaction: see text] A novel approach for the stereocontrolled synthesis of eudesmanolides was developed based on a quasi-biomimetic strategy starting from a functionalized oxabicyclic template, as shown above, by which the first total syntheses of gallicadiol (6) and isogallicadiol (7) were achieved. The key elements of the synthesis include: (1) a facile and stereospecific synthesis of a functionalized epoxy aldehyde intermediate; (2) a mild Lewis acid-mediated stereoselective ene cyclization; and (3) a stereocontrolled gamma-lactonization.