Multicomponent reactions involving tricyclooxonium ylide intermediate: diastereoselective synthesis of mono- and bisalkoxyoctahydro-1,4-benzodioxocin-6(5H)-one frameworks

A highly diastereoselective tandem ring-enlargement and aldol condensation process involving multicomponent reactions of ethereal tricyclooxonium ylide intermediate with alcohols, mono- or dialdehydes in the presence of titanium(iv) isopropoxide is described to furnish alkoxyoctahydro-1,4-benzodioxocin-6(5H)-one ring systems.     

Palladium-catalyzed annulation reactions for diastereoselective cyclopentene synthesis

Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl boronic ester provide substituted cyclopentenes in high yields and, where applicable, diastereoselectivities. This method provides rapid assembly of building blocks for natural product synthesis, including polycyclic lactone and lactam products. Reactions are hypothesized to initiate by conjugate addition of a nucleophilic propargylpalladium complex.     

Asymmetric multicomponent reactions: diastereoselective synthesis of substituted pyrrolidines and prolines

A novel diastereoselective synthesis of substituted pyrrolidines has been developed. Asymmetric multicomponent reactions of optically active phenyldihydrofuran, N-tosyl imino ester, and silane reagents in a one-pot operation afforded highly substituted pyrrolidine derivatives diastereoselectively. The reaction is quite efficient and constructed up to three stereogenic centers in a single operation.     

Multicomponent coupling reactions for organic synthesis: chemoselective reactions with amide-aldehyde mixtures

The acid-catalyzed condensation chemistry of simple amides and aldehydes provides a highly prolific source of diverse reactants for irreversible follow-up reactions. Amide-aldehyde mixtures have been successfully employed in multicomponent syntheses of N-acyl alpha-amino acids (via palladium-catalyzed amidocarbonylation) and various cyclohexene, cyclohexadiene, and benzene derivatives (via the amide-aldehyde-dienophile (AAD) reaction).     

Sequential elimination-cyclopropanation reactions promoted by samarium: highly diastereoselective synthesis of cyclopropylamides

trans-Cyclopropanamides were obtained, in high yield, from 2-chloro-3-hydroxyamides by a sequenced elimination-cyclopropanation process promoted by Samarium/diiodomethane or Samarium diiodide and Samarium/diiodomethane.     

Multicomponent reactions in PEG-400: ruthenium-catalyzed synthesis of substituted pyrroles

An efficient and eco-friendly method for the synthesis of substituted pyrroles has been developed via ruthenium-catalyzed multicomponent reaction of ketone, amine, and ethylene glycol in PEG-400 as solvent medium without using any external ligand. The catalytic system and solvent can be recycled with the same, as well as different, ketones with minimum loss of Ru-catalyst activity.     

Catalytic, asymmetric synthesis and diastereoselective aldol reactions of dipropionate equivalents

The dimer of methylketene can be conveniently prepared in one step and high enantiomeric excess from propionyl chloride, using a catalytic amount of a silylated cinchona alkaloid as a source of chirality. Opening of the dimer with a lithiated sulfonamide affords a beta-ketosulfonimide, which undergoes Sn(II)-mediated aldol reactions to diastereoselectively afford the anti,syn-aldol adduct. Alternatively, reduction of the dimer to the beta-hydroxy ketone, followed by acylation, affords a beta-acyloxyl ketone that undergoes diastereoselective, dialkylboron chloride-mediated aldol reactions to produce the anti,anti-aldol adduct.     

Ruthenium-catalyzed one-pot carbenoid N-H insertion reactions and diastereoselective synthesis of prolines

Aryl- and aliphatic-substituted 3-hydroxyprolines and various other amino esters are conveniently prepared by [RuCl2(p-cymene)]2-catalyzed one-pot intramolecular and intermolecular carbenoid N-H insertion reactions, respectively, and the prolines are formed with high diastereoselectivities. The catalytic reactions are tolerant toward air/moisture, and the product yields are insensitive to the organic solvents used.     

Multicomponent synthesis of dihydrobenzoxazepinones by coupling Ugi and Mitsunobu reactions

Various dihydrobenzo[f][1,4]oxazepin-5-ones have been convergently prepared in 2-3 steps by coupling Ugi and Mitsunobu reactions. Two alternative methodologies were used: in the first one the Ugi condensation was followed by a Mitsunobu cyclization (2 steps); in the second one an intermolecular Mitsunobu reaction was followed by a deprotection step and then by an intramolecular Ugi reaction. Also a "convertible" isocyanide was used.     

Multicomponent reactions involving 2-methyleneaziridines: rapid synthesis of 1,3-disubstituted propanones

Ring opening of 1-alkyl-2-methyleneaziridines 1 or 2 is accomplished with organocopper reagents (R(2)CuLi or RMgX/CuI) in the presence of boron trifluoride diethyl etherate giving 1-substituted propan-2-ones 3-9 in 42-88% yield. Ring opening with RMgCl/CuI in the absence of the Lewis acid allows further alkylation of the metalloenamine (metalated imine) intermediate in a regiocontrolled manner. The sequential formation of two new intermolecular carbon-carbon bonds in this reaction provides a rapid entry into a variety of 1,3-disubstituted propan-2-ones, including 11 and 14-23. The scope and mechanism of this multicomponent reaction (MCR) has been assessed. It is established that this MCR tolerates alkyl, aryl, and benzylic Grignard reagents and a wide range of electrophiles, including alkyl iodides, bromides, and tosylates, as well as epoxides and aldehydes. In addition, gem-dimethyl substitution on the exocyclic double bond of the 2-methyleneaziridine is tolerated. This MCR has been applied to the one-pot synthesis of (Z)-6-heneicosen-11-one, 25, an important sex attractant of the Tussock moth. Using 3-deuterio-1-(1-phenylethyl)-2-methyleneaziridine, 26, we determined that this MCR occurs predominantly by direct ring opening at the sp(3)-hybridized aziridine carbon atom (C-3).     

Four-component reactions for a new diastereoselective synthesis of chiral quaternary centers

The one-pot preparation of chiral homoallylic alcohol and amine derivatives was easily achieved by carbocupration of alkynyl sulfoxides followed by an in situ zinc homologation and reaction with aldehydes or imines. In this process, three new carbon-carbon bonds were created as well as quaternary and tertiary chiral centers with excellent diastereo- and enantioselectivities.     

Multicomponent reactions and ionic liquids: a perfect synergy for eco-compatible heterocyclic synthesis

The efficiency of a chemical synthesis can be nowadays measured, not only by parameters like selectivity and overall yield, but also by its raw material, time, human resources and energy requirements, as well as the toxicity and hazard of the chemicals and the protocols involved. The development of multicomponent reactions (MCRs) in the presence of task-specific ionic liquids (ILs), used not only as environmentally benign reaction media, but also as catalysts, is a new approach that meet with the requirements of sustainable chemistry. The aim of this tutorial review is to highlight the synergistic effect of the combined use of MCRs and ILs for the development of new eco-compatible methodologies for heterocyclic chemistry.     

Highly diastereoselective synthesis of new indolopyrroloquinolines through intramolecular imino Diels-Alder reactions

A new, efficient and highly diastereoselective one-pot synthesis of cis-fused indolopyrroloquinoline derivatives is described through imino Diels-Alder reaction of substituted anilines or naphthylamines with N-prenylated-2-formyl-3-chloroindoles catalyzed by La(OTf)₃.     

Double O-H insertion reactions of cyclic rhodium carbenoids: diastereoselective synthesis of macrocyclic oxindoles

Double O-H insertion reactions of cyclic diazo amides 1 and dihydroxy compounds 2 in the presence of rhodium(II) acetate catalyst have been achieved, which ultimately led to the facile synthesis of prototype bis(3-oxy-1,3-dihydro-2H-indol-2-one) systems. This facile double O-H insertion reaction protocol was successfully applied to synthesize several C₂-symmetric macrocycles having oxindole units incorporated with complete diastereoselectivity.     

Direct catalytic diastereoselective Mannich reactions: the synthesis of protected α-hydroxy-β-aminoketones

The combination of Mg(ClO₄)₂, 2,2′-bipyridine and N-methylmorpholine generates an effective catalyst system for the direct addition of α-carbonate-substituted ketones to aryl N-Ts imines. Methyl-carbonate-substituted ketones deliver acyclic α-hydroxy-β-aminoketone derivates, while ketones substituted with α-iso-propenyl-carbonates furnish cyclic carbamate adducts. In both cases the anti-configured Mannich products dominate.     

Diastereoselective synthesis of strained spiro-cyclopropanooxindoles from cyclic diazoamides

Reaction of cyclic diazoamides and cyclic olefins or heteroaromatic systems using copper(I) triflate as a catalyst furnished a variety of strained spiro-cyclopropanooxindoles in a diastereoselective manner under mild reaction conditions. The effect of copper(I) triflate and rhodium(II) acetate catalysts on the cyclopropanation was also studied.     

Catalyst-controlled diastereoselective hetero-Diels-Alder reactions

[reaction: see text] The diastereoselective hetero-Diels-Alder reaction between Danishefsky's diene and chiral aldehydes is catalyzed by chiral chromium-Schiff base complexes. High levels of catalyst control are obtained in several cases, allowing access to all four stereoisomeric products through appropriate choice of aldehyde and catalyst enantiomers.