The dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat: asymmetric synthesis of α-vinyl-β-hydroxycarboxylic acid derivatives and conversion to α-ethylidene-β-hydroxyesters (β-substituted Baylis-Hillman products)

The synthesis of α-vinyl-β-hydroxyesters and α-ethylidene-β-hydroxyesters (β-substituted Baylis-Hillman products) via the dienolate aldol reaction of (E)-N-crotonoyl C(4)-isopropyl SuperQuat is described. High levels of syn-diastereoselectivity (up to >98% de) are observed for the dienolate aldol reaction with boron enolates, generated either directly with Bu₂BOTf or by transmetalation of the potassium enolate with B-bromocatecholborane. Cleavage of the resultant syn-aldol products from the auxiliary gives α-vinyl-β-hydroxyesters in >98% de and >98% ee. Subsequent isomerisation of the double bond into conjugation provides α-ethylidene-β-hydroxyesters (β-substituted Baylis-Hillman products) in high diastereo- and enantiopurity (≥91:9 [(E):(Z)] and >98% ee).     

Syn selective aldol reactions of titanium and zirconium dienolates.

The low temperature transmetallation of the lithium dienolate of 2-cyclohexene-1-one or 2-cyclopentene-1-one with chlorotitanium triisopropoxide or bis(η⁵-cyclopentadienyl)dichlorozirconium gives the Z,E- titanium or zirconium dienolate. These transition metal dienolates participate in aldol reactions with achiral aldehydes resulting in the direct formation of a syn β-hydroxy enone system.     

Equilibrium between a vinylogous ylide and a phosphonium dienolate zwitterion: vinylogous Wittig olefination versus vinylogous aldol-type reaction

This paper describes the equilibrium established between a phosphonium dienolate zwitterion and a vinylogous phosphorus ylide, and their reactions with aldehydes. The reactions between ethyl 2-methyl-2,3-butadienoate and various aldehydes occur through either a phosphonium dienolate or a vinylogous ylide intermediate, depending on the presence/absence of a Lewis acid and the nature of the phosphine. We observed a rare vinylogous Wittig olefination from the reaction between ethyl 2-methyl-2,3-butadienoate and an electron-deficient aromatic aldehyde in the presence of a stoichiometric amount of an electron-deficient triarylphosphine and a catalytic amount of a Lewis acid (e.g., BF₃·Et₂O). On the other hand, the use of triphenylphosphine, in the absence of a Lewis acid, facilitated vinylogous aldol addition, accompanied by a rare 1,2-aryl phosphorus-to-carbon migration.     

1,3-Rearrangement of ketene-N,O-acetals

Ketene N,O-acetals were prepared stereoselectively and submitted to a Lewis acid-mediated 1,3-rearrangement to afford C-alkylated products. The reactions proceeded in a stereoselective manner to construct a chiral quaternary carbon in high selectivity. The stereochemistry of the quaternary center was found to be opposite to that obtained by an anionic direct dienolate alkylation.     

Intertwined Analytical,Experimental and Theoretical Studies on the Formation and Structure of a Copper Dienolate

The reaction of a silyl dienolate, a Cu(II) salt and TBAT yielding the corresponding copper dienolate is addressed. A combined NMR and cyclic voltammetry analysis first highlight the role of TBAT in the Cu(II) to Cu(I) reduction and the structure of the precatalytic species. From these first results a second set of NMR and theoretical studies enable the determination of the structure and the mechanism of formation of the copper dienolate catalytic species. Finally, we showed that that the copper catalyst promote the E/Z s-cis/s-trans equilibration of the silyl dienolate precursor through a copper dienolate intermediate. All of these results unveil some peculiarities of the catalytic and asymmetric vinylogous Mukaiyama reaction.     

Total synthesis of (3S,4S,2′S)- and (3R,4R,2′S)-viridiofungin A triester

The total synthesis of an alkylcitrate secondary metabolite from the fungi Trichoderma viride is described. An ester dienolate [2,3]-Wittig rearrangement and a S. Julia-Kocienski olefination served as key C/C-connecting transformations. The highly convergent synthesis consists of a longest linear sequence of 17 steps.     

Macroexpansion methodology : Medium ring synthesis based on an eight unit ring expansion process

Treatment of 1,2-(E,E)-di(1-buta-1,3-dienyl)cyclohexanol (21) with potassium hydride in tetrahydrofuran at room temperature resulted in the facile formation of a 14-membered ring dienolate which on kinetic protonation provided cyclotetradeca-3,5,7-trien-1-one. This novel rearrangement which provides the basis for an efficient, eight unit ring expansion method was also observed when 5,8-dimethyl-5-hydroxy-1,3,7,9-decapentaene (28), the acyclic analogue of 21, was treated with potassium hydride in tetrahydrofuran. Methodology for the preparation of 21 and 28 including the preparation of 1-lithio-1,3-butadiene is also described.     

Enantioselective Synthesis of Spirocyclohexadienones by NHC‐Catalyzed Formal [3+3] Annulation Reaction of Enals

The enantioselective synthesis of pyrazolone‐fused spirocyclohexadienones was demonstrated by the reaction of α,β‐unsaturated aldehydes with α‐arylidene pyrazolinones under oxidative N‐heterocyclic carbene (NHC)catalysis. This atom‐economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all‐carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC‐catalyzed generation of chiral α,β‐unsaturated acyl azoliums from enals, and base‐mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.     

Reactions of Verbenone Dienolate with Aromatic Aldehydes

Lithium dienolate of verbenone reacts with aromatic aldehydes to give α- and γ-aldols. Unusual features of the reaction include: selective formation of the γ-aldols under kinetic conditions, absence of deconjugated α-products, high sensitivity to electronic effects and formation of bis-aldols 5.     

Reaction of o-oxazolinylphenyllithium with carbon monoxide. Carbonylative cyclization via an aroyllithium intermediate

The carbonylation of a phenyllithium containing an oxazoline group at the ortho position, followed by quenching with water, afforded a tricyclic compound, 3,3-dimethyl-2,3-dihydrooxazolo[2, 3-a]isoindol-5(9bH)-one, in 91% yield. This reaction proceeded via an intramolecular cyclization of the aroyllithium species, to give the tricyclic dienolate. Treatment of the tricyclic dienolate with electrophiles, such as alkyl halides, aldehydes, ketones, and epoxides gave the substituted oxazolo[2,3-a]isoindolinones in good yield.     

Catalytic Asymmetric Formation of δ‐Lactones from Unsaturated Acyl Halides

Previously unexplored enantiopure zwitterionic ammonium dienolates have been utilized in this work as reactive intermediates that act as diene components in hetero‐Diels–Alder reactions (HDAs) with aldehydes to produce optically active δ‐lactones, subunits of numerous bioactive products. The dienolates were generated in situ from E/Z mixtures of α,β‐unsaturated acid chlorides by use of a nucleophilic quinidine derivative and Sn(OTf)₂ as co‐catalyst. The latter component was not directly involved in the cycloaddition step with aldehydes and simply facilitated the formation of the reactive dienolate species. The scope of the cycloaddition was considerably improved by use of a complex formed from Er(OTf)₃ and a simple commercially available norephedrine‐derived ligand that tolerated a broad range of aromatic and heteroaromatic aldehydes for a cooperative bifunctional Lewis‐acid‐/Lewis‐base‐catalyzed reaction, providing α,β‐unsaturated δ‐lactones with excellent enantioselectivities. Mechanistic studies confirmed the formation of the dienolate intermediates for both catalytic systems. The active Er^III complex is most likely a monomeric species. Interestingly, all lanthanides can catalyze the title reaction, but the efficiency in terms of yield and enantioselectivity depends directly on the radius of the Ln^III ion. Similarly, use of the pseudolanthanides Sc^III and Y^III also resulted in product formation, whereas the larger La^III and other transition metal salts, as well as main group metal salts, proved to be inefficient. In addition, various synthetic transformations of 6‐CCl₃‐ or 4‐silyl‐substituted α,β‐unsaturated δ‐lactones, giving access to a number of valuable δ‐lactone building blocks, were investigated.     

Cyclic sulfamidates as precursors to alkylidene pyrrolidines and piperidines

The reaction of the dienolate of ethyl acetoacetate (and related dienolates) with a range of 1,2- and 1,3-cyclic sulfamidates provides an entry to substituted and enantiopure alkylidenated pyrrolidines and piperidines. These heterocycles function as convenient precursors to heterocyclic beta-amino acid derivatives.     

Direct vinylogous Mannich-type reactions via ring opening and rearrangement of vinyloxiranes

[reaction: see text] The first synthetic application of 2-methyl-2-vinyloxirane as a masked dienolate has been successfully demonstrated in the direct vinylogous Mannich-type reaction with an alpha-imino ester as an electrophile. The Mannich adduct was a useful intermediate en route to cis-5-substituted pipecolinic acid ethyl ester under simple hydrogenation conditions.     

Group‐transfer polymerization of cyclic trimethylsilyl dienolate as a new monomer

This communication reports the group‐transfer polymerization of a cyclic trimethylsilyl dienolate, 2‐(trimethylsilyloxy)furan ( 1 ), initiated with benzaldehyde. The polymerization proceeded in the presence of a tetrabutylammonium salt as the catalyst in THF solvent at 0–50°C. The product was isolated as an ethyl acetate insoluble fraction after acidic work‐up. The structure of the product polymer was determined by means of ¹H NMR, ¹³C NMR, and IR spectroscopy to be polylactone 3 . The mechanism of the polymerization can be explained by a Michael‐type addition of 1 onto the propagating end.     

Facile synthesis of 1,3-diacetyl-2-methylcyclopentene a versatile synthetic intermediate.

Convenient access to 1,3-diacetyl-2-methylcyclopentene $\text{2}$ is reported by three routes: acetylation of methylcyclopentene ( or cyclohexane), condensation of acetylacetone with 1,2-dibromoethane, and the isomerisation of O-acrtylated dienolate of 1-actyl-2-methylcyclopentene. The process of isomerisation provides best results and its mechanism is discussed.     

Controllable highly stereoselective reaction of in situ generated magnesium dienolate intermediates with different electrophiles

In this paper, we have described an efficient controllable stereoselective alpha-acylation and -allylation reaction of the magnesium dienolate intermediates generated in situ from the Fe(III)-catalyzed reaction between 2,3-allenoates and Grignard reagents with different electrophiles to afford 2-acylated or allylated 3( Z)- or ( E)-alkenoates depending on the nature of the electrophiles and reaction conditions. The distinct stereoselectivity may be caused by the isomerization of metallic Z-1,3-dienoate to E-1,3-dienoate via the intermediacy of anti-allylic MgCl and syn-metallic species.     

Alpha,beta-unsaturated delta-lactones from copper-catalyzed asymmetric vinylogous Mukaiyama reactions of aldehydes: scope and mechanistic insights

A direct regio-, diastereo-, and enantiocontrolled access to alpha,beta-unsaturated delta-lactones is described, based on the reaction of a silyl dienolate and an aldehyde in the presence of 10 % of Carreira's catalyst. The scope and limitations of this reaction, as well as mechanistic insights concerning the reactivity of an allyl copper species, are discussed.     

Synthesis of a new,C 2 Symmetric α,α - Bis-(Carboxymethyl) Substituted Nitroxide

The novel, diastereomeric meso- (cis) and (±)- (trans) nitroxides 2,5-dicarboxymethyl-2,5-dimethylpyrrolidine-1-oxyl have been synthesized via a dienolate based strategy. Both optically pure enantiomers of the C ₂ symmetric trans diastereomer have been obtained via resolution of the corresponding amine with dibenzoyltartaric acid.     

AgBF4 catalyzed regio- and stereoselective synthesis of trans α-vinyl-β-amino esters via asymmetric addition of siyl dienolate to sulfinylimines

AgBF₄ catalyzed Mannich-type reactions of siyl dienolate with chiral aryl-substituted (S)-N-tert-butanesulfinylimines has been developed. A class of chiral trans α-vinyl-β-amino esters was obtained in moderate to excellent yields (up to 93%), good diastereoselectiveties (up to 92:8 dr), and complete α-site regioselectivity.     

Unsaturated carboxylic acid dienolates. Michael addition to enones through tandem 1,2-addition - oxy-cope rearrangement.

Michael addition of the dienolate derived from 2-butenoic acid to 1,3-diphenylpro-penone occurs through a 1,2-addition followed by a ³,3-sigmatropic rearrangement. α,γ -re-gioselectivity found for Michael addition to other styryl ketones depends on the steric parameter of the substituents at the carbonyl group, in agreement with the same tandem addition rearrangement mechanism.