RESUMEN
A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.
RESUMEN
A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores. The expeditious assembly of crucial advanced ent-kaurane- and ent-trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization of the alkene/enone and 3-exo-trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with πCâC and πCâO systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.
Asunto(s)
Diterpenos de Tipo Kaurano , DiterpenosRESUMEN
Triacylamines with Cs symmetry have been explored in asymmetric organocatalysis, leading to the development of a novel catalytic enantioselective desymmetrization of prochiral triacylamines by methanolysis under the catalysis of chiral pseudopeptidic guanidine-guanidinium salt having a weakly coordinating anion. This organocatalytic methodology provides an effective approach to the synthetically useful chiral imide-esters with a 1,5-dicarbonyl moiety, and its synthetic potential has been manifested in the asymmetric synthesis of two GABA analogue drugs, (R)-Baclofen·HCl and (S)-Pregabalin.
Asunto(s)
Baclofeno , Ésteres , Catálisis , Guanidina , Imidas , Pregabalina , EstereoisomerismoRESUMEN
The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon has been explored for the first time in a novel iron(III)-catalyzed tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to an expeditious assembly of synthetically important functionalized cyclopenta[b]indoles.
Asunto(s)
Indoles , Hierro , Catálisis , Ciclización , Indolquinonas , Indoles/químicaRESUMEN
A novel strategy based on Cu-catalyzed (4+1) cascade annulation of terminal alkynes as one-carbon synthons with 2-(tosylmethyl)anilines has been developed for the expeditious synthesis of 2,3-disubstituted indoles, in which in situ generations of aza-o-quinone methides and alkynyl-copper(I) species are involved. This annulation provides an effective method for the assembly of synthetically and structurally interesting 2,3-disubstituted indoles.
RESUMEN
A new tandem annulation of p-quinone methides (p-QMs) with ynamides is described. This cascade reaction features a unique combination of (2 + 2) annulation, retro-4π electrocyclization, and imino-Nazarov cyclization, wherein vinyl p-quinone methides (p-VQMs) as one of the key intermediates have been identified chemically. Significantly, an unusual structural reconstruction of p-QMs involving the cleavage of the C5-C6 bond and the late-stage formation of the C4-C6 bond is involved, leading to a methodology development for the construction of functionalized aminoindenes.
RESUMEN
An unprecedented asymmetric catalytic (4 + 2) annulation reaction of aryl-substituted γ-methylidene-δ-valerolactones (GMDVs) with isatin-derived para-quinone methides (p-QMs) has been developed under the catalysis of palladium(0) and (S,S,S)-(-)-Xyl-SKP, offering a new approach for the diastereo- and enantioselective synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles. Significantly, three highly congested contiguous tetrasubstituted carbon atoms embedded in bispirocyclic skeleton, of which two are vicinal quaternary stereogenic centers, are forged in an effective and selective manner (up to 99% yield, up to 95% ee, >20/1 dr). The current reaction represents the first exploration of enantioselective catalytic (4 + 2) annulation forming the six-membered carbocycles in the chemistry of both GMDVs and p-QMs.
RESUMEN
A novel asymmetric catalytic (2+3) annulation of p-quinone methides with CN-substituted trimethylenemethane is described under palladium catalysis, providing an alternative approach for the enantioselective construction of highly functionalized chiral spirocyclopentyl p-dienones. Driven by the significant improvement in the reactivity and enantioselectivity, a novel type of non-C2-symmetric phosphoramidite ligand from the chirality-matched combination of (S)-BINOL and sterically demanding amine derived from l-hydroxyproline is evolved and explored for the protocol presented here.
RESUMEN
Palladium-catalyzed asymmetric [4+5] annulation of ortho-quinone methides (o-QMs) with substituted vinylethylene carbonates (VECs) is described for the first time, giving a novel enantioselective approach to chiral nine-membered benzoheterocycles. Based on this designed [4+5] annulation, an unprecedented silica gel-promoted tandem rearrangement reaction featuring a unique asymmetric aromatic Claisen rearrangement is explored at room temperature, offering a new method for asymmetric construction of all-carbon quaternary stereocenters embedded in chiral functionalized homoallylic alcohols.
RESUMEN
A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters has been developed, providing a new method for expeditious assembly of synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic installation of the pivotal azaspirocyclic core, followed by constructing the benzazepine unit via Witkop cyclization, led to the divergent total syntheses of cephalotaxine and cephalezomine H.
RESUMEN
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 ß-diketone secured the availability of our target molecules.
Asunto(s)
Alcaloides/síntesis química , Alcaloides/química , Estructura MolecularRESUMEN
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.
Asunto(s)
Apocynaceae/química , Productos Biológicos/síntesis química , Alcaloides Indólicos/síntesis química , Productos Biológicos/química , Carbazoles/síntesis química , Carbazoles/química , Catálisis , Alcaloides Indólicos/química , Modelos Moleculares , EstereoisomerismoRESUMEN
We used aryl bromides as inexpensive starting materials to enantioselectively arylate aldehydes in one pot. Aryl bromides readily transfer aryls to aryllithiums with n-butyllithium, successively to triarylaluminums with aluminum chloride, and then to aryltitaniums with titanium isopropoxide. Finally aryltitaniums arylate aldehydes catalyzed by (S)-H8-BINOL-Ti(Oi-Pr)2 in excellent yields and enantioselectivities. The additive TMEDA evidently suppresses the racemic background reaction promoted by LiCl generated from salt metathesis. This procedure represents a cost-effective and operationally convenient method for enantioenriched diarylmethanols.