Vinylogous Aldol Reaction Research Articles

Squaramide-Sulfonamide Organocatalyst for Asymmetric Direct Vinylogous Aldol Reactions.

Asymmetric direct vinylogous aldol reactions of furan-2(5H)-one with aldehydes in the presence of a catalytic amount of novel squaramide-sulfonamide organocatalyst resulted in the corresponding addition products with high to excellent enantioselectivities. This is the first successful report illustrating an example of highly stereoselective reactions using a squaramide-sulfonamide organocatalyst.

Doubly Vinylogous Aldol Reaction of Furoate Esters with Aldehydes and Ketones.

The use of bulky Lewis acids, aluminum tris(2,6-diphenylphenoxide) (ATPH) and aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), in the doubly vinylogous aldol reaction between methyl-5-methyl-2-furoate and aldehydes or ketones is described. These reactions proceed smoothly and in high yields with both enolizable and non-enolizable substrates. This C-C bond-forming reaction enables a new bond construction for the synthesis of functionalized furans.

New Developments in Chiral Cooperative Ion Pairing Organocatalysis by Means of Ammonium Oxyanions and Fluorides: From Protonation to Deprotonation Reactions.

This personal account summarizes our contribution to the ion pairing organocatalysis mainly by use of chiral quaternary or tertiary ammonium fluorides, aryloxides and carboxylates. Starting from an experimental observation, we were able to develop several approaches for the enantioselective protonation of silyl enolates and enol esters giving rise to chiral carbonyl compounds bearing a stereogenic center at the α-position. Moving from protonation to deprotonation reactions, chiral ammonium ion pair catalysts were successfully applied to several asymmetric transformations such as an Henry reaction or a direct vinylogous aldol reaction to cite a few. An outlook of further possible developments in this field of research will also be discussed.

Asymmetric total synthesis of (−)-melotenine A

We have developed a sequential one-pot Mitsunobu/intramolecular aza-Baylis–Hillman reaction to construct the ABCE tetracyclic core of the Strychnos alkaloids and applied this method to the total synthesis of (−)-melotenine A (1), a novel rearranged Aspidosperma alkaloid with potent cytotoxic activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reaction to functionalize the E ring.

A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols

Reported is a rationally-designed one-pot sequential strategy that allows homoallylic alcohols to be employed in a catalytic, asymmetric, direct vinylogous aldol reaction with a series of activated acyclic ketones, including trifluoromethyl ketones, γ-ketoesters, and α-keto phosphonates, in high yields (up to 95%) with excellent regio- and enantio-selectivity (up to 99% ee). This modular combination, including Jones oxidation and asymmetric organocatalysis, has satisfactory compatibility and reliability even at a 20 mmol scale, albeit without intermediary purification.

Organocatalytic Enantioselective Vinylogous Aldol Reaction of Allyl Aryl Ketones to Activated Acyclic Ketones.

The first catalytic asymmetric vinylogous aldol reaction of activated allyls to activated acyclic ketones is disclosed. A variety of activated acyclic ketones, such as trifluoromethyl ketones, α-ketoesters, and α-keto phosphonates, were found to be involved forming diverse γ-selective aldol adducts with high enantioselectivities (up to >99% ee). The method provides an effective, general strategy to access valuable chiral electron-withdrawing group-substituted tertiary hydroxyl-based carboxylic acids.

Thermodynamically driven, syn-selective vinylogous aldol reaction of tetronamides.

A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.

Total Synthesis of Epicolactone

Key words (5+2) cycloaddition - retro-Claisen condensation - vinylogous aldol reaction - cascade reaction - biomimetic synthesis

ChemInform Abstract: Design and Synthesis of a Chiral Seven‐Membered Ring Guanidine Organocatalyst Applied to Asymmetric Vinylogous Aldol Reactions.

Abstract A computationally based design and synthesis of a point chiral seven-membered ring guanidine organocatalyst is reported. The application of this catalyst in asymmetric vinylogous aldol reactions, to form optically active γ-butenolide products with dr’s and er’s up to 90:10 and 97:3 is described.

Design and synthesis of a chiral seven-membered ring guanidine organocatalyst applied to asymmetric vinylogous aldol reactions

A computationally based design and synthesis of a point chiral seven-membered ring guanidine organocatalyst is reported. The application of this catalyst in asymmetric vinylogous aldol reactions, to form optically active γ-butenolide products with dr’s and er’s up to 90:10 and 97:3 is described.

ChemInform Abstract: A General Diastereoselective Catalytic Vinylogous Aldol Reaction Among Tetramic Acid‐Derived Pyrroles.

AbstractThe title process proceeds with good to excellent syn selectivity to provide the corresponding aldol products.

ChemInform Abstract: Tandem N‐Alkylation/Vinylogous Aldol Reaction of β,γ‐Alkenyl α‐Iminoester.

AbstractThis report describes a highly regioselective tandem N‐alkylation/vinylogous aldol reaction of β,γ‐alkenyl α‐iminoesters.

A general diastereoselective catalytic vinylogous aldol reaction among tetramic acid-derived pyrroles.

A catalytic diastereoselective aldol reaction has been developed for N1-arylated/C2-O-silylated/C3-methylated and brominated/C4-O-methylated pyrroles in its reactions with various aldehydes. Syn adducts emerge with regard to the vicinal nitrogen and oxygen heteroatom substituents. The N1-aryl residue undergoes oxidative cleavage, and the C3-bromine atom undergoes palladium-mediated coupling reactions, both without disturbing the newly created stereocenters.

Discovery of novel steroidal pyran–oxindole hybrids as cytotoxic agents

A series of novel steroidal pyran–oxindole hybrids were efficiently synthesized in a single operation through the vinylogous aldol reaction of vinyl malononitrile 3 with substituted isatins involving the construction of C–C and C–O bonds. Some compounds displayed moderate to good cytotoxicity against T24, SMMC-7721, MCF-7 and MGC-803 cells. Compounds 4f and 4i were more potent than 5-Fu against T24 and MGC-803 cells with the IC50 values of 4.43 and 8.45μM, respectively. Further mechanism studies indicated that compound 4i induced G2/M arrest and early apoptosis in a concentration- and time-dependent manner.

Binaphthyl Based Molecules for Asymmetric Organocatalytic Aldol Reactions: Recent Developments from a Successful Record

The careful selection of a suitable chiral backbone is vital for the preparation of any modern ligand for asymmetric catalysis, where binaphthyl based ligands are considered paradigmatic and systematically used in a diversity of asymmetric catalysed reactions, with emphasis for organocatalysis. Due to the vastness of possible organocatalytic applications, this review article is mainly focused on the asymmetric aldol and vinylogous aldol reactions organocatalysed by binaphthyl-based molecules. Special attention is given to catalytic results, particularly on enantio- and diastereoselectivity obtained by the use of the above binaphthyl chiral inductors. Keywords: Aldol, binaphthyl derivatives, organocatalysis, C-C bond, Asymmetric catalysis, BINOL, BINAM, NOBIN.

Tandem N-Alkylation/Vinylogous Aldol Reaction of β,γ-Alkenyl α-Iminoester

This report describes a highly regioselective tandem N-alkylation/vinylogous aldol reaction of β,γ-alkenyl α-iminoesters. The sulfur group improves the regioselectivity of the directed vinylogous aldol reaction, providing a new synthetic method of 3-amino-2-pyrones.

ChemInform Abstract: Direct Asymmetric Vinylogous Aldol Reaction of Allyl Ketones with Isatins: Divergent Synthesis of 3‐Hydroxy‐2‐oxindole Derivatives.

AbstractThe first highly enantioselective direct vinylogous aldol reaction between allyl aryl ketones and isatins is developed using a L‐valine derived bifunctional amino‐thiourea catalyst.

Phosphine-catalyzed formal vinylogous aldol reaction of γ-methyl allenoates with aldehydes: easy access to 1,3-dioxanes and dienols

A phosphine-catalyzed formal vinylogous aldol reaction of γ-methyl allenoates with aldehydes is herein reported, in which the γ-methyl group is directly involved in the carbon–carbon bond formation. Under the catalysis of triarylphosphine (20 mol %) and in the presence of a protic additive, γ-methyl allenoates and aldehydes chemo- and stereoselectively produce functionalized 1,3-dioxanes or dienols in modest to good yields. These chemical transformations provide easy excess to oxy-functionalized enoates and dienoates under very mild conditions.

Recent Advances in Enantioselective Synthesis of γ-Substituted Butenolides via the Catalytic Asymmetric Vinylogous Reactions

The catalytic asymmetric vinylogous-type reactions of γ-butenolides, have received growing attention, because the resulting enantiomerically pure γ-substituted butenolides are versatile building blocks for various natural products and biologically active compounds. The related reactions, such as vinylogous aldol reaction, vinylogous Mannich reaction, vinylogous Michael reactions, as well as allylic alkylation reaction, have been well developed in the past two decades. Both chiral metal complex catalysts and organocatalysts have proven to be useful. Among the plethora of catalytic systems developed so far, vinylogous Mukaiyama-type reactions using 2- silyloxfurans as the nucleophiles are popular for the synthesis of γ-substituted butenolides. On the other hand, the direct version of such reactions using simple butenolides is appreciated in recent years, due to the fact of the synthetic convenience and efficiency. Some advances have also been made in the catalytic direct enantioselective addition of simple butenolides and the analogues. In this microreview, recent progresses regarding the various types of reaction, substrate scope, and probable reaction mechanisms are discussed. In addition, the application of the methodology to the synthesis of natural products and useful intermediates is also presented briefly wherever appropriate.

Synthesis of (+)-Febrifugine and a Formal Synthesis of (+)-Halofuginone Employing an Organocatalytic Direct Vinylogous Aldol Reaction

The enantioselective organocatalytic direct vinylogous aldol reaction of γ-crotonolactone and a suitable aldehyde was utilized in the synthesis of a functionalized γ-butenolide. The γ-butenolide (aldol product) was stereoselectively converted into a 5-aminoalkyl butyrolactone, which isomerized to the key 2,3-disubstituted piperidinone, a common intermediate to (+)-febrifugine and (+)-halofuginone.