A new convenient synthesis of phenanthrene alkaloids from 1-arylmethyl-1,2,3,4-tetrahydroisoquinolines

Hofmann degradation of 1-arylmethyl-1,2,3,4-tetrahydro-2,2-dimethylisoquinolinium iodides with methanolic KOH gave stilbene derivatives, for example, (E)-N-2{2-[2-(phenyl)ethenyl]-4,5-dimethoxyphenyl}ethyl-N,N-dimethylamine. Photochemical electrocyclization of these stilbenes afforded the corresponding phenanthrene alkaloids/phenanthrene derivatives.     

Stereoselective synthesis of 3-mono- and 1,3-disubstituted 4-phenyl-1,2,3,4-tetrahydroisoquinolines

(1S,2S)-(+)-Thiomicamine was transformed in high yield and with high diastereoselectivity into (3R,4R)-4-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and enantiomerically pure (3R,4R)-3-hydroxymethyl-4-phenyl- and (1R,3R,4R)-3-hydroxymethyl-1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline derivatives.     

Quinone methide initiated cyclization reaction: synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinolines

4-Aryl-1,2,3,4-tetrahydroisoquinolines were synthesized in very good yields by in situ generation of p-quinone methides resulting in a novel C-C bond formation.     

A convenient synthesis of olefins via deacylation reaction

A convenient and environmentally-friendly synthetic method of olefins via deacylation reaction is described. The reaction gives olefins by condensation of aldehydes with a variety of 1,3-dicarbonyl compounds in the presence of anhydrous potassium carbonate at room temperature in high yields (70-90%) in one step. The synthetic potential of this strategy can be used as an alternative procedure to the Wittig, Wittig-Horner reactions. The stereochemistry of the resulted olefins was determined by NOE experiment with correct radio frequency and X-ray analysis. The E/Z selectivity of the deacylation reaction depends on the α-substituents of the 1,3-dicarbonyl compounds.     

A convenient synthesis of 2,2-disubstituted 3(2H)-furanones

2,2-Disubstituted 3(2H)-furanones can be prepared readily by 1,2-addition of organometallic compounds to γ,γ-disubstituted β-bromo-α,β-butenolides followed by treatment of the adducts with acid.     

Solid-phase and solution-phase parallel synthesis of tetrahydro-isoquinolines via Pictet-Spengler reaction

An efficient parallel synthesis of 6,7-dimethoxytetrahydroisoquinolines is reported. The key reaction step is 3,4-dimethoxyphenethylimines reacting with acid chlorides to form an N-acyliminium ion intermediate, which undergoes Pictet-Spengler condensation to give the desired products in >80% yield. Both solution-phase and solid-phase synthesis of 6,7-dimethoxytetrahydroisoquinolines are described.     

Hybrid films based on hydroxylated castor oil and titanium(IV) isopropoxide

Novel organic–inorganic hybrid films were synthesized by the reaction of hydroxylated castor oil (HCO) with titanium(IV) isopropoxide (TIP) in which the mass proportions of organic to inorganic precursor varied from 95:5 to 85:15. Films were pre-cured at room temperature under an inert atmosphere and subsequently submitted to thermal curing. The macro- and microscopic properties of the films, including adhesion, hardness, microstructure (SEM and AFM) and thermal properties, were determined as a function of the proportion of HCO to TIP. Morphologic studies showed that the hybrid films were microscopically homogeneous. The hardness and tensile strength of the films increased, with increased concentration of inorganic precursor. All of the films exhibited good adhesion to an aluminum surface.     

Solid-phase synthesis of pyrroloisoquinolines via the intramolecular N-acyliminium Pictet-Spengler reaction

In the present investigation, solid-phase routes toward 1,5,6,10b-tetrahydro-2H-pyrrolo[2,1-a]isoquinolin-3-ones via the intramolecular N-acyliminium Pictet-Spengler reaction are established. Peptide aldehydes generated from their parent N-Boc 1,3-oxazines by acidic reaction conditions undergo intramolecular condensation reactions with the amide N of a solid-supported peptide backbone, thus forming a 1:1 epimeric mixture of a cyclic 5-hydroxylactam, which in turn is in equilibrium with the corresponding intermediate N-acyliminium ion. Provided appropriate acidic reaction conditions, a second ring may be appended via Pictet-Spengler cyclization from the aromatic ring of a neighboring phenylalanine derivative in the peptide sequence. The aromatic substitution pattern of the nucleophilic benzene ring of the phenylalanine derivative and the nature of the acidic reaction media are critically important for the course of the reaction, and both Lewis and Br?nsted acids may be employed to effect the cyclization process. This intramolecular reaction is under strict control of stereoselectivity, and only a single stereoisomer is detected in the crude products. A range of mono-, di-, and trisubstituted phenylalanines with diverse sets of electron-donating and electron-withdrawing substituents, pyrene, and naphthalenes have successfully been brought within the scope of the reaction, thus providing a unique scaffold for combinatorial library synthesis.     

Solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline derivatives employing support-bound tyrosine esters in the Pictet-Spengler reaction

The solid-phase synthesis of 1,2,3,4-tetrahydroisoquinoline-3-carboxamides employing carboxyl-supported, o-alkylated tyrosine esters in a Pictet-Spengler reaction is described. Esterification of [4-(hydroxyphenyl)thiomethyl]polystyrene (Marshall resin) with ethers of N-BOC-L-tyrosine using diisopropylcarbodiimide (DIC) and 4-dimethylaminopyridine (4-DMAP) afforded the solid-supported ester derivatives. Removal of the BOC group with trifluoroacetic acid (TFA) afforded the carboxyl-supported tyrosine ester, which was then treated with paraformaldehyde and TFA to afford the desired solid-supported counterpart. Acylation of the secondary amine with arylsulfonyl chlorides followed by reaction with amines resulted in the formation of the desired 2-arylsulfonyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides. Alternatively, the support-bound tetrahydroisoquinoline-3-carboxylate derivatives could be treated with an aldehyde and a reducing agent to give the corresponding support-bound tertiary amine. Exposure of these resin-bound products to amines afforded the corresponding 2-alkyl-7-alkoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamides after cleavage from the resin. Alternative routes to the desired chemotypes, as well optimization of the conditions for the Pictet-Spengler reaction and the conditions for the acylation and reductive amination of the support-bound secondary amines, are also described.     

Rhodium(II) catalyzed multi-component reactions of aryldiazoacetates with titanium(IV) isopropoxide and imines

Rh₂(OAc)₄ catalyzed diazo decomposition of aryldiazoacetates in the presence of titanium(IV) isopropoxide generated oxonium ylide intermediates. Trapping of the oxonium ylide intermediates with imines occurred subsequently via a nucleophilic addition. The three-component reaction of aryldiazoacetates, titanium(IV) isopropoxide, and imines gave α-alkoxyl-β-amino acid derivatives with C-N/C-C bond formation in a single step. Extension of the study to a four-component reaction with in situ generated imine was also investigated.     

A convenient and expeditious synthesis of 3-(N-substituted) aminocoumarins via palladium-catalyzed Buchwald-Hartwig coupling reaction

A convenient protocol for the rapid and efficient synthesis of 3-(N-substituted) aminocoumarins is described. The synthetic route developed involves the Pd-catalyzed C-N coupling reaction from readily available 3-bromocoumarin derivatives in the presence of the catalytic system Pd(OAc)₂/Xantphos. Under these conditions, a series of nucleophiles including amides, sulfonamides, carbamates and functionalized amines, have been successfully reacted to afford the coupling products in fair to good yields.     

Microwave-assisted, solvent-free synthesis of 1-(α- or β-hydroxynaphthyl)-1,2,3,4-tetrahydroisoquinolines by the Mannich reaction

As a new extension of the Mannich reaction of naphthols, 1-(hydroxynaphthyl)-substituted 1,2,3,4-tetrahydroisoquinolines were synthesized by the nucleophilic addition of 1- or 2-naphthol to 3,4-dihydroisoquinolines under solvent-free conditions, using microwave irradiation. The additions to 3-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline proved to be a highly diastereoselective processes, resulting in the cis isomers as the main or the only products.     

A facile synthesis of symmetrical 1,1-disubstituted ethylenes

The reaction of ethyl trimethylsilylacetate with two equivalents of a Grignard reagent in ether followed by treatment with acid gives 1,1-disubstituted ethylenes in excellent yield.     

Total synthesis of (+)-yohimbine via an enantioselective organocatalytic Pictet-Spengler reaction

The binolphosphoric acid-catalyzed Pictet-Spengler reaction of an N-(5-oxy-2,4-pentadienyl)tryptamine derivative with methyl 5-oxo-2-(phenylseleno)pentanoate leads to the tetrahydro-β-carboline in a 92:8 enantiomeric ratio. This product is easily converted into the substrate for a stereoselective intramolecular Diels-Alder reaction of the type earlier reported by Jacobsen. These two key steps constitute the basis for a nine-step total synthesis of (+)-yohimbine from tryptamine. A similar asymmetric Pictet-Spengler reaction was applied to the synthesis of an intermediate in the recent total synthesis of corynantheidine by Sato.     

A general procedure for the asymmetric synthesis of 3-aryl-1,2,3,4-tetrahydroisoquinolines

A general procedure for the asymmetric synthesis of 3-aryl-1,2,3,4-tetrahydroisoquinolines with any desired substitution pattern at both aromatic rings is reported. The methodology relies on the deoxygenation of 3-aryl-1,2,3,4-tetrahydroisoquinolin-4-ols 1a–e, which can be easily prepared from chiral non-racemic arylglycines under ionic hydrogenation conditions The target heterocycles are obtained as almost enantiomerically pure compounds. Further experiments allow establishing that this transformation occurs via S_N1 mechanism in which a carbocationic intermediate species is firstly formed and afterwards it undergoes rapid reaction with a nucleophilic hydride carrier to afford the reduction product.     

A convenient access to 2,4-disubstituted quinazolines via one-pot three-component reaction under mild conditions†

Abstract

A new and practical method has been developed for the synthesis of 2,4-disubstituted quinolines via one-pot three-component reaction of o-amino arylketones, aldehydes and ammonium acetate in high yields by using DDQ in CH₃CN under mild conditions. Neutral conditions, atom economy, easy work-up procedures and compatible with different functional groups are the salient features of this protocol.     

A convenient synthesis of quinazoline derivatives via cascade imino-Diels-Alder and oxidation reaction

<正>Quinazoline derivatives were synthesized fromα-iminoesters via a cascade imino-Diels-Alder and then oxidation reaction catalyzed with CuBr_2.This method provided a new strategy for preparing quinazoline derivatives which may be useful in the synthesis of heterocyclic intermediates.     

Phthalonimides (1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolines) of potential biological interest

A new simple method for the preparation of phthalonimides (1,3,4-trioxo-1,2,3,4-tetrahydroisoquinolines), consisting of the selenium dioxide-oxidation of the appropriate homophthalimides, has been devised; the thiosemicarbazones and other derivatives of phthalonimides of possible biological interest (as potential antibacterial, antiviral, or immunosuppressive agents) have been synthesized.     

Reversible double insertion of aryl isocyanates into the Ti-O bond of titanium(IV) isopropoxide

The insertion of phenyl isocyanate into titanium isopropoxide leads to the formation of a dimeric complex [Ti(OⁱPr)₂(μ-OⁱPr){C₆H₅N(OⁱPr)CO}]₂ (1) which has been structurally characterized. Reaction of titanium isopropoxide with two and more than 2 equiv. of phenyl isocyanate is complicated by competitive, reversible insertion between the titanium carbamate and titanium isopropoxide. The ligand formed by insertion of phenyl isocyanate into the titanium carbamate has been structurally characterized in its protonated form C₆H₅N{C(OⁱPr)O}C(O)N(H)C₆H₅ (3aH). Insertion into the carbamate is kinetically favored whereas insertion into isopropoxide gives the thermodynamically favored product.