π-Lewis-Base-Catalyzed Asymmetric Vinylogous Umpolung Reactions of Cyclopentadienones and Tropone.

We disclose that the carbonates of 4-hydroxy-2-cyclopentenones can form π-allylpalladium-based 1,2-carbodipoles, which isomerize to interesting η2 -Pd0 -cyclopentadienone complexes. Compared with the labile parent cyclopentadienone, the HOMO energy of the related η2 -complex was significantly raised via the back-bonding of Pd0 as a π-Lewis base, rendering the uncoordinated C=C bond an electron-richer dienophile in inverse-electron-demand aza-Diels-Alder-type reactions with diverse 1-azadienes. The vinylogous (aza)Morita-Baylis-Hillman or cross Rauhut-Currier addition to (imine)carbonyls or activated alkenes, respectively, was also realized to afford chiral [4+2] or [2+2] cycloadducts, respectively, after trapping the re-generated π-allylpalladium species. New C1 -symmetric ligands from simple chiral sources were developed, exhibiting high stereoselectivity even with racemic substrates via an unusual dynamic kinetic resolution process. Besides, tropone could be similarly activated by a Pd0 complex.

Asymmetric Allylic Alkylation with Deconjugated Carbonyl Compounds: Direct Vinylogous Umpolung Strategy.

An atom-economic and highly efficient vinylogous umpolung strategy is developed for deconjugated carbonyl compounds, which generate electron-deficient π-allylpalladium complexes with Pd(OAc)2 under ligand-free conditions. In cooperation with a chiral-phosphonium-based phase-transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3-substituted oxindoles are furnished under O2 atmosphere. The γ- or even remote ϵ-regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures effectively. The Mukaiyama dienol silyl ether can be utilized similarly, indicating that the current active π-allylpalladium species results from tautomerization of the PdII -dienolate intermediate.

Palladium-catalysed fragmentary esterification-induced allylic alkylation of allyl carbonates and cyclic vinylogous anhydrides.

An unprecedented palladium-catalysed fragmentary esterification-induced allylic alkylation (FEAA) of cyclic vinylogous anhydrides (CVAs) and allyl carbonates has been disclosed. The protocol features broad sp3-rich scaffold tolerance, rendering highly functionalized 1,6 and 1,7-dicarbonyls in up to high yields and diastereoselectivities. Three-component FEAA is also well tolerant to generate 1,6-dicarbonyls through the addition of extra O/N-nucleophiles. Furthermore, cyclic allyl carbonate-involved FEAA provides an efficient approach for the synthesis of structurally complex medium-sized rings.

Enantioselective Synthesis of Ten-Membered Lactones via Palladium-Catalyzed [5 + 5] Annulation.

Ten-membered lactones are the core units of many biologically active natural products but with a great synthetic challenge. Based on the principle of vinylogy, novel types of cyclic vinylogous anhydrides have been designed as five-carbon carbonyl synthons, further applied in [5 + 5] annulation with vinylethylene carbonates under chiral palladium catalysis. This strategy features excellent regioselectivity, mild conditions, and broad substrate scope, affording a range of spiro ten-membered lactones bearing oxindole and pyrrolidinone motif in excellent yield (up to 99%) with moderate to high enantioselectivity (up to 89% ee).

Pd-Catalyzed Tandem [5 + 2] Cycloaddition/Ring Contraction of Phthalide-Derived Alkenes and Vinylethylene Carbonates for the Construction of Benzo-[5,5]-spiroketal Lactones.

An annulation of phthalide-derived activated alkenes is initially disclosed in this work. Specifically, we have developed an unprecedented [5 + 2] cycloaddition/ring-contraction tandem process of activated tetrasubstituted alkenes derived from phthalides or butyrolactone with vinylethylene carbonates under Pd(0) catalysis. Differing from the traditional spirolactonization strategy, this method renders an efficient and mechanistically distinct approach to benzo-[5,5]-spiroketal lactones and [5,5]-spiroketal lactones bearing two vicinal tetrasubstituted centers with high diastereoselectivity.

Ligand-Controlled Regiodivergent Asymmetric [5 + 2] and [3 + 2] Annulations of Vinyl Indoloxazolidones Catalyzed by Palladium.

Here, we present palladium-catalyzed regiodivergent asymmetric annulations of vinyl indoloxazolidones, which can act as 1,5-carbodipoles or 1,3-carbodipoles by tuning the chiral ligands and conditions, in the assemblies with sulfamate-derived cyclic imines and even activated alkenes. A diversity of polycyclic products are generally constructed with high regio- and enantioselectivity.

Cu(I)-Catalyzed Asymmetric α-Allenylation of Activated Ketimines with 3-Butynoates.

An asymmetric α-regioselective allenylation reaction of activated ketimines with 3-butynoates is disclosed under Cu(I) catalysis, probably via the generation of nucleophilic γ-allenylcopper species in the presence of diisopropylethylamine. A broad range of imines, derived from diverse ketones such as isatins, pyrazolediones, isoquinoline-1,3,4-triones, and even trifluoromethyl alkynyl ketones, can be utilized, generally affording the corresponding α-allenyl amine derivatives in high yields (≤97%) with excellent enantioselectivities (≤99% ee).

Asymmetric Cascade Assembly of 1,2-Diaza-1,3-dienes and α,ß-Unsaturated Aldehydes via Dienamine Activation.

A cascade vinylogous 1,6-Michael addition/1,4-proton shift/aza-Michael addition/hemiaminal formation sequence of 1,2-diaza-1,3-dienes and ß-substituted 2-butenals has been developed under the influence of dienamine activation of a chiral secondary amine. This method exhibits high regio- and chemoselectivity and provides an efficient and straightforward approach to bicyclic l,8-diazabicyclo[3.3.0]octane skeletons with a tetrasubstituted stereogenic center with fair to excellent enantioselectivity.

Divergent Cyclization Reactions of Morita-Baylis-Hillman Carbonates of 2-Cyclohexenone and Isatylidene Malononitriles.

Zwitterionic dienolates generated from Morita-Baylis-Hillman carbonates of cyclohexen-2-one and a phenolic tertiary amine catalyst underwent divergent cyclization reactions with isatylidene malononitriles. A new [4 + 2] stepwise cyclization process was disclosed to deliver complex bridged spirooxindoles after the initial δ'-regioselective Rauhut-Currier-type reaction with N-methyl electrophiles by the catalysis of ß-isocupreidine, while spirooxindoles incorporating an aromatic chromene motif were generated with N-MOM acceptors in the presence of α-isocupreine through different domino transformations.