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It is reported herein that by exploiting the commonly shared bicyclic decahydroquinoline motif, a gold-catalyzed enamide-alkyne cycloisomerization reaction is developed to access tricyclic cores in a simple way. These tricyclic cores further serve as an advanced platform for the divergent enantioselective collective total syntheses of five Lycopodium alkaloids, belonging to three different structural types, in a concise and protecting-group-free fashion. The key transformations in the second phase include: 1) a transannular reductive Heck cyclization for installation of the azepane ring in fawcettidine, fawcettimine, and lycoposerramine Q; 2) a domino Mukaiyama hydration/Grob fragmentation process for construction of the ten-membered lactam system in phlegmariurine B; 3) a Fukuyama one-pot protocol for the construction of the 2-pyridone motif in lycoposerramine R. The newly developed strategy is expected to pave the way for the synthesis of other structurally related Lycopodium alkaloids.

Described herein is a B(C

A strategy for the synthesis of cis-hydrocarbazole with a C3 quaternary carbon center has been developed through nickel/Lewis acid dual-catalyzed arylcyanation. A wide array of cis-hydrocarbazoles was accessed with high diastereoselectivities and atom economies in a good yield. The rich chemistry of the installed nitrile group was demonstrated in the preparation of tryptamine- and tryptophol-derived cis-hydrocarbazoles.

The first total synthesis of the Euphorbia diterpenoid pepluanol B in both racemic and enantioenriched form involves 20 steps from a known bicyclic diol. This synthesis features an unprecedented bromo-epoxidation to control the eight-membered-ring conformation. In addition, salient reactions for the construction of the tetracyclic backbone include a sterically challenging aldol reaction to establish the quaternary center, a ring closing metathesis (RCM) to forge the eight-membered ring, and a diastereoselective cyclopropanation to assemble the embedded cyclopropane motif.

An efficient visible light photoredox catalyzed aerobic deprotection of 1,3-oxathiolanes using organic dye Eosin Y as a photocatalyst is disclosed. The deprotection procedure features the use of a metal-free catalyst, mild conditions, a broad range of substrate scope, and good functional group tolerance. 35 examples were tested under the standard conditions and most of them afforded the deprotected products in modest to high yields.

Diquinane or bicyclo[3.3.0]octane is a conspicuous structural unit existing in the carbo-frameworks of a wide range of natural products such as alkaloids and terpenoids. These diquinane-containing molecules not merely exhibit intriguing architectures, but also showcase a broad spectrum of significant bioactivities, which draw widespread attention from the global synthetic community. During the past decade, with an aim to accomplish the total syntheses of such specified cornucopias of natural products, a variety of elegant strategies for construction of the diquinane ring system have been disclosed. In this Minireview, the achievements on this subject in the timeline from 2010 to June 2020 are demonstrated and it is discussed how the diquinane unit is strategically forged in the context of the specific target structure. In addition, impacts of the selected works to the field of natural product total synthesis is highlighted and the particular outlook of diquinane-containing natural product synthesis is provided.

The first total synthesis of Gardneria oxindole alkaloid (-)-gardmultimine A has been achieved in 19 steps from d-tryptophan in a fully stereocontrolled manner. This synthesis features (1) an Ir-catalyzed regioselective C-H borylation/oxidation sequence to introduce the C12 methoxyl group, (2) a stereocontrolled oxidative rearrangement of indole to construct the spirooxindole motif, and (3) an Au(I)-catalyzed transannular Conia-ene-type 6-exo-dig cyclization to establish the azabicyclo[2.2.2]octane skeleton and the exocyclic E-alkene with exclusive stereoselectivity.

An efficient synthesis of complex tetracyclic compounds is developed which relies on a gold(I)-catalyzed tandem 1,2-acyloxy migration/[3 + 2] cycloaddition/Friedel–Crafts type cyclization reaction of linear enynyl esters. The reaction proceeds under extremely mild conditions in good to excellent yields (54%–88%) with a dr value of up to 20 : 1.

The first asymmetric total synthesis of aspidosperma alkaloid (+)-winchinine B was achieved in 12 steps from commercially available materials. A new synthetic strategy which features an efficient aza-Michael addition, a ruthenium-catalyzed transfer dehydrogenation, and an intramolecular palladium-catalyzed oxidative coupling was adopted to install the ABC tricycle system. A one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition developed by our group was utilized to construct the D ring moiety.

The first total synthesis of conosilane A, a densely oxygenated nonisoprenoid sesquiterpene, has been achieved through stereoselective intramolecular radical cyclization and double utilization of site-selective C–H functionalization as key steps, thus simplifying the synthetic endeavors in natural product synthesis.

A sequential reaction combining N-heterocyclic carbene (NHC) and N-hydroxyphthalimide (NHPI) catalysis allowed for the upstream by-product NHPI, which was generated in the NHC-catalyzed cycloaddition reaction, to act as the catalyst for a downstream nitrogen-to-carbon sulfonyl migration reaction. Enantiomeric excess of the major product in the cycloaddition reaction remained intact in the follow-up sulfonyl migration reaction.

The first asymmetric total synthesis of kravanhin B has been accomplished with a linear reaction sequence of 13 steps starting from (R)-(-)-carvone. The synthesis features an intramolecular aldol cyclization to construct the desired cis-fused decalin skeleton and an acid-catalyzed dehydration and olefin isomerization to install the γ-butenolide ring.

A visible-light-mediated radical addition of alkynoates to generate 3-bromocoumarins by using N-bromosuccinimide as the bromo source has been accomplished. This procedure provides a bromo radical addition/spirocyclization/ester migration cascade reaction under very mild reaction conditions without using any catalyst or strong oxidant and does not need high reaction temperature. Furthermore, the reaction can also be enlarged to the gram scale, and the product 3-bromocoumarins can be further applied in the synthesis of complex compounds.

A visible-light promoted single electron oxidation of ether enabled by photoredox catalysis has been accomplished. This procedure initiates a novel radical insertion/cyclization cascade reaction to generate phenanthridines and isoquinolines from easily available isocyanides under mild reaction conditions.

An efficient metal-free Mizoroki-Heck type reaction of di- and tri-substituted alkenes with 2-chloro-dithiane has been developed under ambient pressure of air or using a relatively low loading of BF3·Et2O. This study represents a new environmentally friendly method for the syntheses of dithianyl-substituted alkene derivatives via a radical oxidative coupling process.

Present methods to synthesize 1,3-dithiane molecules require either harsh reaction conditions or highly specialized reagents. We have developed a catalytic dithioacetalization process that directly gains access to the corresponding 1,3-dithianes using aldehydes and 2-chloro-1,3-dithiane in a highly efficient manner. This methodology is beneficial due to mildness of the reaction conditions, and the dithioacetaliation process results in good to excellent yields by using 15 mol % of an iron catalyst.

A highly efficient strategy for the formation of medium-sized-ring ethers and amines based on a gold-catalyzed cascade reaction, involving enynyl ester isomerization and intramolecular [3+2] cyclization, has been developed. Various multisubstituted medium-sized-ring unsaturated ethers and amines were obtained through this transformation. This method represents one of the relatively few transition metal catalyzed intramolecular cycloaddition reactions for medium-sized ring synthesis.

An alternative method to an iron-catalyzed radical oxidative cross-coupling reaction followed by 2-chloro-1,3-dithiane and aryl olefins for the synthesis of β-chloro substituent 1,3-dithiane products is presented. The described method has the advantage of mildness of the reaction conditions and tolerates a variety of functional groups. Preliminary mechanistic studies have confirmed the first example of a coupling of 1,3-dithiane with unactivated alkenes that proceeds via an iron-catalyzed oxidative radical intermediate along the reaction pathway.

Domino intramolecular Diels-Alder (IMDA) reactions towards the 6/6/5/5 fused tetracyclic natural products were developed in satisfactory yield and high stereoselectivity. Four rings, six contiguous stereocenters and four C-C bonds were formed in a single operation. 4-epi-Hydromitchellene B was also synthesised efficiently via this strategy.

N-Heterocyclic carbene-catalyzed formal [3+2] annulation of alkynyl aldehydes and nitrosobenzenes has been reported. This transformation provided the novel C–X bond formation under mild conditions ...

The construction of reduced graphene oxide or graphene oxide (GO) with magnetic nanoparticles has gained more and more attention due to its promising and wide applications in catalysis, photoelectric materials, biomedical fields and so on. The synthesis of reduced graphene oxide (RGO) or graphene magnetic nanoparticle nanocomposites with well-dispersed decorated particles is still a challenge. Herein, we first report a simple method to prepare graphene–Fe3O4 with uniform Fe3O4 NPs based on decomposition of Fe(CO)5 on the surface of graphene oxide. The main novelty of this work is that the decomposition products of Fe(CO)5 reacted with GO leading to the formation of graphene–Fe3O4. The resulting sample can be easily manipulated by an external magnetic field and exhibits excellent catalytic activity in the A3-coupling reaction. A diverse range of propargylamines were obtained in a moderate to high yield under mild conditions. The separation and reuse of graphene–Fe3O4 were very simple, effective and economical.

An effective synthesis of structurally diverse benzazocines was accomplished in good to excellent chemical yields (55-82 %) through a gold(I)-catalyzed cascade reaction involving tandem 1,2-acyloxy shift/[3+2] cycloaddition of terminal 1,9-enynyl esters. The reaction proceeds under extremely mild conditions and represents one of the relatively few transition-metal-catalyzed intramolecular cycloaddition reactions for the synthesis of benzazocines.

(-)-Delta(8)-trans-Tetrahydrocannabinol was synthesized with high regio- and stereoselectivity through S(N)2' addition of an arylcyanocuprate to the optically pure enol silyl ether of alpha,beta-epoxy-cyclohexanone.

Functionalized α-hydroxy carbonyl compounds were prepared from various aldehydes and allylic acetates via a multicomponent reaction, which were catalyzed by N-heterocyclic carbene and Pd catalysts in one pot.

The intramolecular nucleophilic addition reaction of acyl anion equivalents to enol ethers is described, which was catalyzed by N-heterocyclic carbenes generated in situ from readily available thiazolium salt. In this transformation, benzofuranones were obtained in excellent yield. In combination with our previous work, the precise mechanistic elucidation for the formation of benzofuranones has been further investigated. A labeling experiment implied that the transformation proceeds through a nucleophilic addition mechanism.

The facile total synthesis of the antimalarial nonenolide 1 is reported. The convergent strategy features the use of reactions such as Sharpless asymmetric dihydroxylation, aldol addition, Mitsunobu reaction, and ring-closing metathesis (RCM).

A mild and efficient method for the deprotection of the TBS and THP ethers is described. A wide variety of TBS ethers as well as THP ethers can be easily deprotected to the corresponding parent hydroxyl compounds by employing a catalytic amount of tris(4-bromophenyl)aminium hexachloroantimonate (TBPA(+center dot)SbCl(6)(-)) in methanol at room temperature in good yield. (C) 2008 Elsevier Ltd. All rights reserved.

The first total synthesis of hydramicromelin B is described. An AuCl3/AgOTf-catalyzed intramolecular reaction was used as key step for the construction the coumarin ring.

The facile total synthesis of the (−)-Heliconol A (ent-1) as well as its diastereoisomer 18 is described, in which different reaction sequences lead to different results. The osmylation of 15 followed by hydrolysis afforded a single isomer 18, otherwise, a mixture of ent-1 and 18 resulted. Other important processes include the catalytic asymmetric CBS reduction and induced osmylation. The synthesis proceeded with a sequence of 11 steps, affording ent-1 in 9.0% and 18 in 22% overall yield, respectively.

A facile protocol is developed for the cyclization reaction of ether and amine substrates to form 8- and 9-membered ring products in moderate to good yields.

Notable advantages of the title process are mild reaction conditions and good to excellent yields.

An efficient, convergent approach for the total synthesis of aigialomycin D 1 is described. Key features of the synthetic strategy include (a) a Sharpless asymmetric epoxidation reaction and selective opening of a 2,3-epoxy alcohol to elaborate the two hydroxy-bearing stereogenic centers at the C5′ and C6′ positions; (b) a Kocienski modified Julia protocol to construct the two E-configured double bonds; and (c) Yamaguchi macrolactonization to acccess the 14-membered macrocyclic ring.

The enantioselective synthesis of 7-butyl-6,8-dihydroxy-(3R)-pentylisochroman-1-one has been achieved for the first time in which Sharpless asymmetric dihydroxylation is the key step.

The enantioselective synthesis of the phenolic sesquiterenses (S)- and (R)-curcuphenol is reported. The key step in this synthesis is the asymmetric conjugate addition using a readily available enantiomerically pure sulfoxide as the chiral auxiliary.

The stereoisomers of 3,4-dihydroxy-6-methoxy-2,2-dimethyl-chroman 1a–c and 3,4,7-trihydroxy-6-acetyl-2,2-dimethyl-chroman 2a–c were conveniently prepared for the first time via a synthesis in which Sharpless asymmetric dihydroxylation and Jacobsen’s catalytic asymmetric epoxidation are the key steps.

This paper describes a new class of chiral oxazolidinone ketone catalyst for asymmetric epoxidation. High ee values have been obtained for a number of cyclic and acyclic cis-olefins. The epoxidation was stereospecific with no isomerization observed in the epoxidation of acyclic systems. Encouragingly high ee values have also been obtained for a number of terminal olefins. Mechanistic studies show that electronic interactions play an important role in stereodifferentiation.

The first and efficient total synthesis of (±)-dasyscyphin D was achieved in 9 steps with 22.6% overall yield. The key steps involved a PtCl(2)-catalyzed pentannulation reaction and acid-catalyzed double Robinson annulations.

[structure: see text]. Ketones with a fused oxazolidinone were synthesized and investigated to determine the electronic effect of the substituents at alpha-positions of ketone catalysts on the Baeyer-Villiger oxidation and catalytic properties for asymmetric epoxidation. These new ketones give high yields and ee's with only 1-5 mol % catalyst. The current studies further show that the electronic effect is very important for the ketone-catalyzed epoxidation.

A method for direct Henry reaction and Knoevenagel condensation promoted by guanidine organocatalyst has been developed. The relationship of the structure and amount catalyst has been investigated.

8,9-Dihydroxydihydromagnolol 5 was synthesized in four steps in which the synthesis of magnolol 4 was improved and the absolute configuration of 5 was confirmed as ( R ).

On the move: A novel PtCl2-catalyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration reaction was developed, which was shown to be controlled by substitution effects. Using this method, a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields.

Ring around the rosie: The effective enantioselective synthesis of the antimalarial nonenolide title compounds was achieved in a convergent strategy. Oxy-Michael addition reaction was used to introduce the chiral methoxy group at C-4, and ring-closing metathesis (RCM) reaction (53 % yield) facilitated the key construction of the 10-membered ring.

On the move: A novel PtCl2-catalyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration reaction was developed, which was shown to be controlled by substitution effects. Using this method, a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields.

PdCl2-catalyzed intramolecular Heck reaction was conducted in ionic liquid, 1-n-butyl-3-methylimidazolium tetraborate ([BMIm] BF4), substituted benzofurans were obtained in modest to satisfactory yields. The ionic liquid containing Pd catalyst can be used four times with a little loss of activity.

Pd/C-catalyzed Heck reaction was conducted in ionic liquid 1-octanyl-3-methylimidazolium tetrafluoroborate ([OMIm]BF4) in absence of phosphine ligand, which was promoted by microwave irradiation. The ionic liquid containing catalyst system can be used five times with a little loss of activity.

Reverse to success! A new formal [3+2] annulation reaction combining alkynyl aldehydes and β,γ-unsaturated α-ketoesters has been disclosed by using a NHC-catalyzed/Lewis acid mediated strategy. This cooperative catalysis strategy first allows the "allenolate" intermediate as a nucleophilic synthon at the β-position to react with activated electrophilic reagents by an addition reaction as the key C-C bond-forming step.