Diènamines hétérocycliques—II : Condensation de la base de fischer sur des aldéhydes aliphatiques satures. Formation d'azatriènes

Aliphatic aldehydes react with Fischer's base, 1,3,3-trimethyl-2-methylene indoline, to give new dienamines. When using acetaldehyde a substituted dienamine resulting from the reaction of two molecules of Fischer's base with the aldehyde is isolated. All products react with tosylated isonitrosomalonic derivatives yielding azatrienes which possess high absorption coefficients.     

Efficient synthesis of highly functionalized vinylogous thiol esters

A series of vinylogous thiol esters 2,3 and 2,6-dioxo-1,2,5,6-tetrahydropyridines (cyclic vinylogous thiol esters) 4 were prepared in high to excellent yields from the tandem reaction of readily available α-alkenoylketene diethylthioacetals 1 and diethyl malonate. A plausible mechanism, which involves a base catalyzed retro-Michael ring opening of cyclohexanenes 2 to give vinylogous thiol ester 3, is disclosed.     

Configurational isomer mixtures and c-protonation in some sterically crowded enaminones

Acylation of 1,3,3-trimethyl-2-methyleneindoline (Fischer's Base) gives enaminone derivatives which show unusual C-protonation and exist in solution as mixtures of the $\text{cis}$-s-$\text{cis}$ and $\text{cis}$-s-$\text{trans}$ configurations.     

Regioselection in the alkylation of trimethylsilylallyl anion - stereoselective synthesis of disubstituted alkenes

The regioselection in the alkylation of trimethylsilylallyl anion can be controlled by the use of Schlosser's base to give predominately γ-product with trans-geometry at the double bond. Application of this approach to the synthesis of Z-9-tricosene and the Gypsy moth sex pheromone is demonstrated.     

Remarkable regioselectivities in the course of the synthesis of two new Luotonin A derivatives

Ethyl 4-oxo-3,4-dihydroquinazoline-2-carboxylate reacts selectively with trimethylaluminium-activated 2-amino- or 4-aminobenzoic acid ethyl esters to give the corresponding anilides without self-condensation of the aminobenzoate building blocks. After propargylation, the quinazolinones were treated with Hendrickson's reagent, but only the para-substituted ester was found to undergo the expected [4 + 2] cycloaddition reaction, affording a new Luotonin A derivative. A different regioselectivity was observed with the ortho-substituted ester which affords a benzoxazinone under identical conditions. When the ester group in the ortho-substituted intermediate is replaced with a nitrile function, the outcome of the reaction with Hendrickson's reagent depends on the absence or presence of a base (DBU), yielding either a triphenylphosphonium-substituted iminobenzoxazine or a 4-cyano-substituted Luotonin A derivative.     

Aza- and carbo-[3+3] annulations of exo-cyclic vinylogous amides and urethanes. Synthesis of tetrahydroindolizidines and an unexpected formation of hexahydroquinolines

[3+3] Annulations of exo-cyclic vinylogous amides and urethanes with vinyl iminium salts are described here. We observed an intriguing dichotomy in their reaction pathways. For pyrrolidine- and azepane-based vinylogous amides or urethanes, aza-[3+3] annulation would dominate to give tetrahydroindolizidines, whereas, unexpectedly, for piperidine-based vinylogous amides or urethanes, carbo-[3+3] annulation was the pathway, leading to hexahydroquinolines. The origin for such a contrast is likely associated with a switch in the initial reaction pathway between C-1,2-addition and C-1,4-addition.     

Synthesis of oligoribonucleotides by use of S,S-diphenyl n-monomethoxytrityl ribonucleoside 3'-phosphorodithioates

The fully protected ribonucleotide units (6a–d) have been synthesized in 42–62% overall yields by the 5- or 6-step reactions. The dimethoxtrityl, monomethoxytrityl, tetrahydropyran-2-yl, and phenylthio groups were introduced onto the 5'-OH, exo-amino, 2'-OH, and 3'-phosphoryl functions, respectively. The units were converted to the OH or phosphodiester components by treatment with trifluoroacetic acid or with phosphinic acid-triethylamine. Both the components were appropriately coupled by means of mesitylenedisulphonyl chloride 3-nitro-1,2,4-triazole to give dimers in high yields. This method was successfully applied to the synthesis of GpUpApUpUpApApUpAp, i.e. the 5'-terminal base sequence of brome mosaic virus m RNA No. 4 filament.     

Aromatization of aliphatic compounds—III: Abnormal michael addition to diethyl-α-acetyl-α'-methyl succinate

While isobutyl vinyl ketone reacts with α-acetyl-α'-methyl succinate to give a normal Michael adduct, the Mannich base or its quaternary derivative as a source of vinylketonc gives the butenolide derivative 8a. Isobutyl cyclohexenoneacetic acid (1b) previously stated to be the reaction product was present only as a by-product. When α-acetyl-α'-methyl succinate is treated with acrylic acid derivatives only butenolides 8c–8f were obtained.     

Use of the electrophilic c-arylation by aryllead triacetates in the construction of synthons for aizoaceae and amaryllidaceae alkaloid synthesis

The vinylogous β-keto esters, ethyl 2-methyl-4-oxocyclohex-2-ene-carboxylate (Hagemann's Ester) (4), ethyl 4-oxocyclohex-1-ene-carboxylate (7a) and its double bond isomer (7b), undergo regiospecific arylation with aryllead triacetates at C1; reaction of the mixture of isomers (7a) and (7b) with aryllead compounds (5a), (5c) and (5d) provides intermediates for the synthesis of (±)-o-methyl-joubertiamine (1), (±)-mesembrine (2) and (±)?lycoramine (3) respectively.     

The reactions of some bromo-derivatives of compounds having reactive methylene groups with thioureas,and of some resultant thiouronium salts with base

Whereas α-bromocarbonyl compounds react with thiourea to give thiazole derivatives, bromomalononitrile and bromobis(phenylsulphonyl)methane underwent protodebromination. With N,N,N',N'-tetramethylthiourea many of the bromo-compounds gave thiouronium salts but protodebromination sometimes supervened. N,N'-Disubstituted thioureas provided examples of salt formation, protodebromination and cyclisation reactions. The only thiouronium salt to provide an ylide on treatment with base was the S- [bis(phenylsulphonyl)methyl]-N,N,N',N'-tetramethythiouronium bromide. N,N'-Disubstituted salts gave isothioureas rather than ylides. Thiouronium dicyanomethylide underwent cyclisation rather than a Wittig reaction when heated with p-nitrobenzaldehyde, and the aldehyde condensed with the resultant 2-aminothiazole.     

Diastereoselective alkylations of oxazolidinone vinylogous glycolates

A highly Z-selective isomerization (double bond migration) was observed when oxazolidinone vinylogous glycolate was exposed to a strong base to give N-acyl oxazolidinone, bearing an electron rich olefin. The corresponding enolate was exposed to alkyl halides to provide alkylated compounds on the γ-position with respect to OBn group, with high regioselectivity and moderate diastereoselectivity. However, the nature of the chiral oxazolidinone leads to a significant increase in the reaction diastereoselectivity. A stereospecific formation of cis-olefin was also observed in these alkylated compounds.     

Silicon tetrachloride in organic synthesis: new applications for the vinylogous aldol reaction

This paper describes a novel and efficient methodology for vinylogous aldol reactions based on SiCl₄ catalysis. According to the nucleophilicity Mayr's scale, vinylogous aldol reaction of Chan's diene proved to be effective by using catalytic amount of SiCl₄, without any other promoter. On the contrary, the SiCl₄/Lewis base system has been conveniently exploited for the efficient and selective vinylogous reaction of less nucleophilic Danishefsky's diene and 2-trimethylsilyloxyfuran (TMSOF). Indeed, a number of Lewis bases, such as sulfoxides, formamides and phosphoramides have been successfully used as SiCl₄ promoters. TMSOF and silyloxydienes, resulting from 2,2,6-trimethyl-[1,3]-dioxin-4-one derivatives, required stoichiometric amount of SiCl₄, while vinylogous aldol reaction of Chan's and Danishefsky's dienes took satisfactorily place in the presence of catalytic or sub-stoichiometric amount of catalyst.     

Recent progress on direct catalytic asymmetric vinylogous reactions

Direct catalytic asymmetric vinylogous reaction serves as a powerful tool to introduce stereocenter(s) at the γ- or/and even more remote position(s) of the vinylogous products in an atom-economical and efficient way. A variety of direct catalytic asymmetric vinylogous reactions with broad substrate scope and mild reaction conditions has been developed. Both metal catalysis and organocatalysis contributed in this field and led to the vinylogous products in high stereoselectivity. These vinylogous reactions provided efficient pathways for the synthesis of highly functionalized optically pure compounds, especially these with potential biological activity and pharmacological activity. This digest paper mainly focuses on the most recent developments in this field, including both nucleophilic addition and nucleophilic substitution.     

Electrophilic Activation of α,β‐Unsaturated Amides: Catalytic Asymmetric Vinylogous Conjugate Addition of Unsaturated γ‐Butyrolactones

Although catalytic asymmetric conjugate addition reactions have remarkably advanced over the last two decades, the application of less electrophilic α,β‐unsaturated carboxylic acid derivatives in this useful reaction manifold remains challenging. Herein, we report that α,β‐unsaturated 7‐azaindoline amides act as reactive electrophiles to participate in catalytic diastereo‐ and enantioselective vinylogous conjugate addition of γ‐butyrolactones in the presence of a cooperative catalyst comprising of a soft Lewis acid and a Brønsted base. Reactions mostly reached completion with as little as 1 mol % of catalyst loading to give the desired conjugate adducts in a highly stereoselective manner.     

Condensation of enolates with O-ethyl pyrrolidonium salts: An alternative to the orthoamide condensation

O-Ethyl-N-substituted pyrrolidonium fluoroborate salts were condensed under basic conditions with active methylene compounds to give vinylogous carbamates and cyanamides.     

Fluorinated 2-benzoylcyclohexane-1,3-diones and their vinylogous acyl chlorides in the reactions with primary and secondary amines

The reaction of 5,5-dimethyl-2-[(3-fluoro- and 4-fluoro)benzoyl]cyclohexane-1,3-diones with primary and secondary amines affords their exocyclic enamine derivatives. Under similar conditions 5,5-dimethyl-2-(2-fluorobenzoyl)]cyclohexane-1,3-dione undergoes dehydrofluorination and intramolecular cyclization to give 3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthene-1,9-dione. The reaction of vinylogous substitution of the enol derivatives of the fluorinated 5,5-dimethyl-2-benzoylcyclohexane-1,3-diones (vinylogous acyl chlorides) with amines results in the formation of the endocyclic enaminoderivatives.     

Tröger's base analogs. New structural units for the preparation of chiral hosts and metal ligands.

Several Tröger's base analogs are prepared and presented as practical, structurally well defined and unique “folded” armatures for the preparation of chelating or macrocyclic host molecules.     

Silyldienolates in Organocatalytic Enantioselective Vinylogous Mukaiyama-Type Reactions: A Review

Mukaiyama aldol, Mannich, and Michael reactions are arguably amongst the most important C–C bond formation processes and enable access to highly relevant building blocks of various natural products. Their vinylogous extensions display equally high potential in the formation of important key intermediates featuring even higher functionalization possibilities through an additional conjugated C–C double bond. Hence, it is much desired to develop highly selective vinylogous methods in order to enable unconventional, more efficient asymmetric syntheses of biologically active compounds. In this regard, silyl-dienolates were discovered to display high regioselectivities due to their tendency toward γ-additions. The control of the enantio- and diastereoinduction of these processes have been for a long time dominated by transition metal catalysis, but it received serious competition by the application of organocatalytic approaches since the beginning of this century. In this review, the organocatalytic applications of silyl-dienolates in asymmetric vinylogous C–C bond formations are summarized, focusing on their scope, characteristics, and limitations.     

An attempt to approach the solutions of the N-electron CNDO hamiltonian for conformational studies of conjugated systems

While dealing with the same N-electron hamiltonian, the SCF approximation and the third order PCILO results completely disagree about the conformation of conjugated systems. An attempt is made, using the CIPSI algorithm, to approach the exact solution of the N-electron CNDO hamiltonian for the butadiene molecule starting from either a priori localized, SCF localized or SCF delocalized MO's. The partial CI's performed from SCF delocalized MO's give arbitrary results when increasing the number of doubly excited determinants and Pancir?'s recent results is fortuitous; on the contrary the results obtained from a priori and SCF localized MO's have better convergence and consistence; from our best calculations the final solution seems to be a rather flat potential curve, the stable minimum being the trans planar minimum, with a second gauche minimum for θ = 120-150° (ΔH ≈ 1 kcal/mole), separated by a weak barrier (ΔH ≈ 2 kcal/mole). The third order PCILO solution is in much better agreement with this estimate of the exact solution than the SCF one.     

1-Naphthyl-TADDOL/Emim BF<Subscript>4</Subscript>: A new catalytic system for the asymmetric addition of Chan’s diene to aromatic aldehydes

A new organocatalytic system was tested as a promoter for the asymmetric addition of Chan’s diene to aldehydes under solvent-free conditions. This new organocatalyst generated in situ by mixing 1-naphthyl-TADDOL derivative and Emim BF₄ was able to give enantioenriched vinylogous aldols and hetero-Diels-Alder cycloadducts. A mechanistic investigation through the detection of nonlinear effects confirmed the involvement of the ionic liquid in the formation of a new catalytic supramolecular species.