A simple and concise catalytic asymmetric entry to tetrahydroxanthenones

The first catalytic asymmetric synthesis of tetrahydroxanthenones is presented. The simple organocatalytic enantioselective domino reactions between salicylic aldehyde derivatives and α,β-unsaturated cyclic ketones proceed with excellent chemoselectivity to give the corresponding tetrahydroxanthenones in moderate to good yields and high enantioselectivities.     

Quadruple domino organocatalysis: an asymmetric aza-michael/michael/michael/aldol reaction sequence leading to tetracyclic indole structures with six stereocenters

Quadruple domino/Wittig-one pot: An organocatalytic, asymmetric, three-component quadruple cascade, which leads to tetracyclic double-annulated indole derivatives, is described. The domino products were further derivatized by aldehyde olefination under one-pot conditions to obtain complex isoindolo[2,?1-a]indole derivatives bearing six stereogenic centers in a highly stereoselective fashion.     

Lipase-catalyzed domino kinetic resolution of alpha-hydroxynitrones/intramolecular 1,3-dipolar cycloaddition: a concise asymmetric total synthesis of (-)-rosmarinecine

The title domino reactions were developed to directly provide tetrahydrofuro[3,4-c]isoxazole derivatives (5 and 9) in > or =90% ee from racemic alpha-hydroxynitrones (2 and 6), which were used in the concise asymmetric total synthesis of (-)-rosmarinecine .     

Coinage Metal-Catalyzed Asymmetric Reactions of ortho-Alkynylaryl and Heteroaryl Aldehydes and Ketones

Coinage metals have become the metal of choice due to their excellent catalytic activity in organic transformation processes. Combining various chiral ligands and coinage metals became a productive area of research and access to heterocyclic derivatives according to an efficient and sustainable manner. This review was devoted to the various recently developed coinage metal-catalyzed domino processes of ortho-alkynylaryl and heteroaryl aldehydes and ketones leading to functionalized heterocycles. Various gold chiral complexes were presented, and methods of preparations of chromenes along with indoles were covered. Ag-chiral complexes are also prone to interesting activities such as cyclization followed by reduction and functionalization with enolizable ketones or (diazomethyl)phosphonate. Asymmetric Cu-catalyzed domino cyclization and asymmetric transfer hydrogenation reactions efficiently led to functionalized chromenes. Some remarkable examples involving copper associated with ruthenium in the context of a cyclization and asymmetric hydrogenation process were also presented.     

Stereoselective trimerization of [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols and p-quinamines

[reaction: see text] The asymmetric synthesis of pentacyclic derivatives was achieved in a single step starting from enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or the nitrogen analogue, through a domino sequence involving four conjugate additions in excellent yields. Eight new stereogenic centers were created in one step and in a highly diastereoselective manner.     

Organocatalytic asymmetric domino aza-Michael-Mannich reaction: synthesis of tetrahydroimidazopyrimidine derivatives

Highly substituted tetrahydroimidazopyrimidine derivatives with three chiral centers have been synthesized for the first time using an organocatalytic asymmetric domino aza-Michael-Mannich reaction of α,β-unsaturated aldehydes and N-arylidene-1H-imidazol-2-amines. This efficient approach furnishes the products in good yields (42-87%) with excellent stereoselectivities (>20:1 dr, up to >99% ee).     

Asymmetric domino Michael–Henry reaction of 1,2-diones with nitroolefins catalyzed by a chiral bisoxazolidine–Ni(acac)2 complex

The asymmetric domino Michael–Henry reaction of 1,2-cyclohexadione with nitroolefins catalyzed by chiral ligand bisoxazolidine 1 and Ni(acac)₂ has been developed. This process provided highly functionalized chiral bicycle[3,2,1] octane derivatives with the generation of four new stereogenic centers in high yields (76–99%), and with excellent enantioselectivities (up to 99%) and good diastereoselectivities (up to 9:1) under mild reaction conditions. The procedure presented is simple and makes this method suitable for practical use.     

Facile and efficient synthesis of lactols by a domino reaction of 2,3-epoxy alcohols with a hypervalent iodine(III) reagent and its application to the synthesis of lactones and the asymmetric synthesis of (+)-tanikolide

The domino reaction of 2,3-epoxy-1-alcohol derivatives, namely tetrasubstituted 2,3-epoxy-1-alcohols and 2- or 3-alkyl trisubstituted 2,3-epoxy-1-alcohols, with PhI(OCOCF(3))(2) in the presence of H(2)O is described in detail. In this reaction, several types of lactol derivatives can be directly obtained from the 2,3-epoxy-1-alcohol derivatives in a single operation. The obtained lactols were successively converted into the corresponding lactones. This reaction is applicable to the construction of optically active lactone compounds. The asymmetric total synthesis of (+)-tanikolide, an antifungal marine natural product, has been effectively achieved by using this reaction.     

Enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction for the synthesis of 1,2-dihydroquinolines using pepsin from porcine gastric mucosa

An unprecedented enzyme-catalyzed asymmetric domino aza-Michael/aldol reaction of 2-aminobenzaldehyde and a,b-unsaturated aldehydes is achieved. Pepsin from porcine gastric mucosa provided mild and efficient access to diverse substituted 1,2-dihydroquinolines in yields of 38%–97% with 6%–24%enantiomeric excess(ee). This work not only provides a novel method for the synthesis of dihydroquinoline derivatives, but also promotes the development of enzyme catalytic promiscuity.     

Highly enantioselective synthesis of 2H-1-benzothiopyrans by a catalytic domino reaction

A highly enantioselective catalytic asymmetric synthesis of 2H-1-benzothiopyrans is presented. The organocatalytic asymmetric domino reactions between 2-mercaptobenzaldehyde and α,β-unsaturated aldehydes proceed with excellent chemo- and enantioselectivities to give the corresponding pharmaceutically valuable benzothiopyrans in high yields with 91-98% ee.     

α-Acyloxynitroso dienophiles in [4+2] hetero Diels-Alder cycloadditions: mechanistic insights

α-Acyloxynitroso derivatives are a class of heterodienophiles leading to valuable 3,6-dihydro-1,2-oxazines or the corresponding aminoalcohols in good yields. The discovery that a β-oxygenated moiety led to a domino [4+2] cycloaddition/σ_N-O bond cleavage in the presence of a catalytic amount of Lewis acid was investigated in detail, through kinetic profiling of the reaction both in the absence and presence of a promoter. These studies showed that the role of the Lewis acid was to accelerate the σ_N-O bond cleavage thereby promoting a highly reproducible sequence. In addition, our preliminary results on an asymmetric version of this domino sequence are reported.     

Direct Synthesis of Benzofuro[2,3‐b]pyrroles through a Radical Addition/[3,3]‐Sigmatropic Rearrangement/Cyclization/Lactamization Cascade

A straightforward synthetic method for the construction of benzofuro[2,3‐b]pyrrol‐2‐ones by a novel domino reaction through a radical addition/[3,3]‐sigmatropic rearrangement/cyclization/lactamization cascade has been developed. The domino reaction of O‐phenyl‐conjugated oxime ether with an alkyl radical allows the construction of two heterocycles with three stereogenic centers as a result of the formation of two C?C bonds, a C?O bond, and a C?N bond in a single operation, leading to pyrrolidine‐fused dihydrobenzofurans, which are not easily accessible by existing synthetic methods. Furthermore, asymmetric synthesis of benzofuro[2,3‐b]pyrrol‐2‐one derivatives through a diastereoselective radical addition reaction to a chiral oxime ether was also developed.     

Enantioselective heterocyclic synthesis of spiro chromanone-thiochroman complexes catalyzed by a bifunctional indane catalyst

Novel asymmetric domino reactions of benzylidenechroman-4-ones and 2-mercaptobenzaldehydes for efficient construction of spiro chromanone-thiochroman complexes were accomplished with high yields and excellent selectivities via a novel bifunctional indane catalyst.     

Phosphine‐Catalyzed Domino Reactions: A Route to Functionalized Bicyclic Skeletons

A novel strategy that involves phosphine‐catalyzed sequential [2+3] and [3+2] annulation reactions was developed. In this domino reaction, γ‐substituted allenoates were used as novel C₄ synthons, and the bicyclic cyclopenta[b]dihydrofuran derivatives were produced in good to excellent diastereoselectivities and yields under mild conditions. Furthermore, preliminary studies on an asymmetric variant of this reaction proceeded with moderate enantioselectivity.     

A one-pot organocatalytic asymmetric entry to tetrahydrothioxanthenones

A simple catalytic asymmetric synthesis of tetrahydrothioxanthenones is presented. The organocatalytic enantioselective domino reactions between 2-mercaptobenzaldehyde and α,β-unsaturated cyclic ketones proceed with excellent chemoselectivity to give the corresponding tetrahydrothioxanthenones in high yields and moderate to good enantioselectivities.     

Iridium-catalyzed allylic vinylation and asymmetric allylic amination reactions with o-aminostyrenes

An Ir-catalyzed allylic vinylation reaction of allyl carbonates with o-aminostyrene derivatives has been realized, providing skipped (Z,E)-diene derivatives. With (E)-but-2-ene-1,4-diyl dimethyl dicarbonate as the substrate, an efficient enantioselective synthesis of 1-benzazepine derivatives via an Ir-catalyzed domino allylic vinylation/intramolecular allylic amination reaction has been developed. Mechanistic studies of the allylic vinylation reaction have been carried out, and the results suggest that the leaving group of the allylic precursor plays a key role in directing the reaction pathway. Screening of various allylic precursors showed that Ir-catalyzed reactions of allyl diethyl phosphates with o-aminostyrene derivatives proceed via an allylic amination pathway. A subsequent ring-closing metathesis (RCM) reaction of the amination products led to a series of enantiomerically enriched 1,2-dihydroquinoline derivatives. Their utility is indicated by an asymmetric total synthesis of (-)-angustureine.     

Convenient synthesis of hexasubstituted benzene derivatives via DABCO promoted domino reaction of arylidene malononitrile and dialkyl but-2-ynedioate

A convenient synthetic protocol for the hexasubstituted benzene derivatives was successfully developed by DABCO promoted domino reaction of arylidene malononitrile with two molecules of dialkyl but-2-ynedioates. The domino reaction resulted in tetraalkyl 6-cyano-[1,1′-biphenyl]-2,3,4,5-tetracarboxylates in good to high yields. This formal [2 + 2 + 2] cycloaddition was believed to proceed with sequential nucleophilic addition, Michael addition, annulation and aromatization processes.     

Unifying metal- and organocatalysis for asymmetric oxidative iminium activation: a relay catalytic system enabling the combined allylic oxidation of alcohols and prolinol ether catalyzed iminium reactions

A multicatalytic system consisting of tetrapropylammonium perruthenate/N-methylmorpholine N-oxide (TPAP/NMO) as oxidant, and diarylprolinol TMS-ether as chiral amine catalyst, has been developed and applied in the efficient construction of valuable chiral molecules. The one-pot domino reactions elaborated in the present study are based on the in situ generation of α,β-unsaturated aldehydes from allylic alcohols and their subsequent use in various asymmetric transformations (e.g., cyclopropanation, Michael addition, Michael addition/acetalization). TPAP as a substrate-selective redox catalyst is well tolerated by the amine catalyst and the domino reactions proceed in good yields and high enantioselectivities. The compatibility of metal and organocatalysis presented herein widens the scope of asymmetric iminium catalysis.     

One-pot organocatalytic domino Michael/alpha-alkylation reactions: direct catalytic enantioselective cyclopropanation and cyclopentanation reactions

The development of one-pot organocatalytic domino Michael/alpha-alkylation reactions between bromomalonates or bromoacetoacetate esters and alpha,beta-unsaturated aldehydes is presented. The chiral-amine-catalyzed reactions with bromomalonates as substrates give access to the corresponding 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99 % ee. The catalytic domino Michael/alpha-alkylation reactions between 4-bromo-acetoacetate and enals provide a route for the synthesis of functionalized cyclopentanones in good to high yields with 93-99 % ee. The products from the organocatalytic reactions were also reduced with high diastereoselectivity to the corresponding cyclopropanols and cyclopentanols, respectively. Moreover, one-pot combinations of amine and heterocyclic carbene catalysis (AHCC) enabled the highly enantioselective synthesis of beta-malonate esters (91-97 % ee) from the reaction between bromomalonates and enals. The tandem catalysis included the catalytic domino reaction followed by catalytic in situ chemoselective ring-opening of the 2-formylcyclopropane intermediates.     

A new domino Knoevenagel-hetero-Diels-Alder reaction: an efficient catalyst-free synthesis of novel thiochromone-annulated thiopyranocoumarin derivatives in aqueous medium

An efficient catalyst-free synthesis of novel pentacyclic thiochromone-annulated thiopyranocoumarin derivatives is achieved via domino Knoevenagel-hetero-Diels-Alder reaction of 4-hydroxy dithiocoumarin and O-acrylated salicylaldehyde derivatives in H₂O as solvent. The products are formed in good yields with high regio- and stereo-selectivity.