A novel enantioselective [4 + 2] annulation of the allenoates having a unique positive ortho-effect with in situ generated ortho-quinone methides has been developed under the catalysis of Cinchona alkaloid. This chiral amine-catalyzed reaction provides an alternative route to asymmetric catalytic construction of synthetically interesting, highly functionalized chiral chromans in good to excellent enantioselectivities (up to 97% ee).

The first total syntheses of Lycopodium alkaloids palhinine A, palhinine D, and their C3-epimers have been divergently achieved through the use of a connective transform to access a pivotal hexacyclic isoxazolidine precursor. A microwave-assisted regio- and stereoselective intramolecular nitrone–alkene cycloaddition was tactically orchestrated as a key step to install the crucial 10-oxa-1-azabicyclo[5.2.1]decane moiety embedded in the conformationally rigid isotwistane framework, demonstrating the feasibility of constructing the highly strained medium-sized ring by introduction of an oxygen bridging linker to relieve the transannular strain in the polycyclic scaffold. Subsequent N–O bond cleavage provided the synthetically challenging nine-membered azonane ring system bearing the requisite C3 hydroxyl group. Late-stage transformations featuring a chemo- and stereoselective reduction of the pentacyclic β-diketone secured the availability of our target molecules.

A novel base-mediated tandem spirocyclopropanation/rearrangement reaction of vinyl p-quinone methides (p-VQMs) with sulfonium salts is described. The unprecedented reactivity of p-VQMs was explored for the first time in the spiroannulation cascade, providing a stereoselective approach to the construction of synthetically interesting, densely functionalized spirocyclopentenyl p-dienones.

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.

A proposed strategy for constructing the nine-membered azonane ring system embedded in the isotwistane framework of palhinine A has been preliminarily studied on the basis of an azidoketol fragmentation reaction together with a SmI2-mediated pinacol coupling. Albeit negative results for building the azonane ring scaffold via a tertiary azidoketol fragmentation, the present exploration strategically provided an endeavor to probe the synthetically challenging issue in the synthetic study of palhinine A.

A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently.

A novel strategy based on phase transfer catalysis for the diastereoselective and enantioselective direct assembly of unsymmetric β,β-diaryl-α-amino acid esters via 1,6-conjugate addition of para-quinone methides and glycine derivatives is described. This protocol also provides an alternative route to the synthetically interesting functionalized chiral tetrahydroisoquinoline and its analogues.

An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.

The selective transalkylation of N-methyl tertiary amines with 3,4-dibromobutenolides is described. The N-methyl group of the parent tertiary amines was replaced by alkenyl units of the butenolides; and a series of butenolide-containing tertiary enamines were obtained in moderate to good yields. Interestingly, the product 2b has shown a promising anticancer activity against HeLa cell lines (IC50 = 0.19 μmol/L).A novel transalkylation of N-methyl tertiary amines with 3,4-dibromobutenolides is described, and a series of butenolide-containing tertiary enamines were obtained in moderate to good yields. Interestingly, the product 2b has shown a promising anticancer activity against HeLa cell lines (IC50 = 0.19 μmol/L).

The stereoselective, expedient assembly of the key functionalized isotwistane (bridged tricyclo[4.3.1.03,7]decane) system, 5/6/6 ring, with contiguous quaternary stereocenters in Lycopodium alkaloid palhinine A and its analogues via an intramolecular Diels–Alder strategy is described.

The first regiodivergent opening of unbiased epoxides (REO) providing the ring-opened products in high enantiomeric excess from racemic and exceptionally high enantiomeric excess from enantioenriched substrates in a double asymmetric process has been devised. It constitutes a more general case of the very important enantioselective openings of meso-epoxides. The dependence of the selectivity of ring opening on the epoxide’s substitution pattern was studied.tert-Butyl 3-((4S,5R)-3-propyloxiran-2-yl)propanoateC12H22O3Ee = 80%[α]D=-6.4[α]D=-6.4 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5R)tert-Butyl 3-((4S,5R)-3-pentyloxiran-2-yl)propanoateC14H26O3Ee = 88%[α]D=-11.9[α]D=-11.9 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5R)tert-Butyl 2,2-dimethyl-3-((4S,5R)-3-pentyloxiran-2-yl)propanoateC16H30O3Ee = 85%[α]D=-0.3[α]D=-0.3 (c 2.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5R)(R)-tert-Butyl 4-hydroxyoctanoateC12H24O3Ee = 94%[α]D=+0.7[α]D=+0.7 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 5-hydroxyoctanoateC12H24O3Ee = 99%[α]D=-0.5[α]D=-0.5 (c 0.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 4-hydroxynonanoateC13H26O3Ee = 79%[α]D=+1.0[α]D=+1.0 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 5-hydroxynonanoateC13H26O3Ee = 79%[α]D=-1.0[α]D=-1.0 (c 0.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 4-hydroxydecanoateC14H28O3Ee = 98%[α]D=+1.5[α]D=+1.5 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 4-hydroxydecanoateC14H28O3Ee = 98%[α]D=+1.2[α]D=+1.2 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(S)-tert-Butyl 5-cyclohexyl-4-hydroxypentanoateC15H28O3Ee = 70%[α]D=-6.0[α]D=-6.0 (c 1.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-tert-Butyl 5-cyclohexyl-5-hydroxypentanoateC15H28O3Ee = 94%[α]D=-10.5[α]D=-10.5 (c 0.5, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(R)-tert-Butyl 4-hydroxy-2,2-dimethyldecanoateC16H32O3Ee = 99%[α]D=+3.2[α]D=+3.2 (c 2.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-tert-Butyl 4-hydroxy-2,2-dimethyldecanoateC16H32O3Ee = 94%[α]D=+0.6[α]D=+0.6 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-6-Propyltetrahydro-2H-pyran-2-oneC8H14O2Ee = 81%[α]D=+33.3[α]D=+33.3 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-5-Butyldihydrofuran-2(3H)-oneC8H14O2Ee = 94%[α]D=-40.2[α]D=-40.2 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(S)-6-Butyltetrahydro-2H-pyran-2-oneC9H16O2Ee = 79%[α]D=-36.4[α]D=-36.4 (c 4.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(S)-5-Pentyldihydrofuran-2(3H)-oneC9H16O2Ee = 79%[α]D=+28.3[α]D=+28.3 (c 4.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-6-Pentyltetrahydro-2H-pyran-2-oneC10H18O2Ee = 89%[α]D=+41.6[α]D=+41.6 (c 1.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(R)-5-Hexyldihydrofuran-2(3H)-oneC10H18O2Ee = 98%[α]D=-33.0[α]D=-33.0 (c 0.9, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-3,3-Dimethyl-6-pentyltetrahydro-2H-pyran-2-oneC12H22O2Ee = 94%[α]D=-24.9[α]D=-24.9 (c 2.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(R)-5-Hexyl-3,3-dimethyldihydrofuran-2(3H)-oneC12H22O2Ee = 62%[α]D=+13.7[α]D=+13.7 (c 2.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)(S)-6-(Butoxymethyl)tetrahydro-2H-pyran-2-oneC10H18O3Ee = 92%[α]D=-46.0[α]D=-46.0 (c 3.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) tentatively(S)-5-(2-Butoxyethyl)dihydrofuran-2(3H)-oneC10H18O3Ee = 81%[α]D=+9.6[α]D=+9.6 (c 2.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R) tentatively

The asymmetric catalytic 1,6-addition of p-QMs with racemic oxindoles under the bifunctional catalysis of C2-symmetric dimeric Cinchona-derived squaramide is described. This tertiary amine-squaramide catalyzed reaction provides a diastereoselective and enantioselective approach to the effective assembly of diverse diarylmethine-substituted oxindoles having vicinal tertiary and quaternary stereocenters.