Β-hydroxy Ketones Research Articles

Catalytic, Asymmetric Synthesis and Diastereoselective Aldol Reactions of Dipropionate Equivalents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Lewis acid promoted aldol reaction of fluorinated silyl enol ethers from new fluoroacetylsilane derivatives

New fluorinated silyl enol ethers with various trialkylsilyl groups were synthesized. Various fluorinated β-hydroxy ketones were synthesized by Lewis acid promoted aldol reaction of silyl enol ethers with diverse aldehydes. Reactivity of various trialkylsilyloxy groups toward Lewis acid was also studied.

A green look at the aldol reaction

Aldol reactions have been and are widely applied for the preparation of β-hydroxy aldehydes, β-hydroxy ketones or α,β-unsaturated aldehydes or ketones through addition or addition-elimination reactions of aldehydes and ketones. The study of the aldol reaction from the point of view of its greenness must have in mind first of all that a general synthetic method must be based on complete and efficient conversions of well defined selectivity and that greenness is more a term for comparison than an absolute kind of qualification. This comparison, when referred to the aldol reaction, applies here to the diverse modifications of the reaction. Thus, the original poorly selective, but highly atom economic catalytic procedures, have been improved by several authors by introduction of stoichiometric forms of activation in the search for better selectivities. However, the success in these improvements has been accompanied by higher levels of hazard and waste. The study of the greenness of the aldol reaction is completed by a short overview of recent contributions intended to achieve efficient, safe and clean conversions that are susceptible to becoming general green synthetic procedures. Interesting contributions are highlighted for reactions carried out under solvent-less conditions, in water, ionic liquids and supercritical fluids, with activation by microwaves, or with use of heterogeneous catalysis and especially of biocatalysis and biomimetic catalysis. Promising methods based on reduction of unsaturated ketones or on rearrangement of allylic alcohols have also recently been described.

Studies Towards the Synthesis of Superstolide A: An Aldol-Based Construction of an Advanced C1-C5/C20-C26 Segment

Based on a boron-mediated syn aldol reaction of an alanine-derived ethyl ketone with an α-chiral aldehyde partner, an advanced intermediate for superstolide A was assembled in a highly stereocontrolled fashion. Controlled 1,3-anti reduction of the resulting β-hydroxy ketone gave the characteristic amino diol stereopentad of superstolide, followed by a Takai olefination and esterification of the C23 hydroxyl to provide the elaborated C1-C5/C20-C26 segment 3.

Enantioselective total syntheses of several bioactive natural products based on the development of practical asymmetric catalysis.

I present herewith enantioselective total syntheses of several bioactive natural products, such as (-)-strychnine, (+)-decursin, (-)-cryptocaryolone diacetate, (-)-fluoxetine, and aeruginosin 298-A, based on practical asymmetric catalyses (Michael reaction, epoxidation, and phase-transfer reaction) that I developed with co-workers in Prof. Shibasaki's group over the past 5 years. In the first part of this review, I discuss the great improvement of catalyst efficiency in an ALB-catalyzed asymmetric Michael reaction of malonate and application to the pre-manufacturing scale (greater than kilogram scale) and enantioselective total synthesis of (-)-strychnine with the development of novel domino cyclization. To broaden the substrate generality of the Michael reaction, we developed a highly stable, storable, and reusable La-O-linked-BINOL complex. Further extension of the reaction using beta-keto ester as a Michael donor was achieved with the development of a La-NR-linked-BINOL complex, thereby improving indole alkaloid syntheses. In the second section, I discuss enantioselective total synthesis of (+)-decursin using catalytic asymmetric epoxidation. To achieve the synthesis, we developed a new La-BINOL-Ph(3)As = O (1:1:1) complex catalyst system, which has much higher reactivity and broader substrate generality than the previously developed catalyst systems. This allowed us to achieve catalytic asymmetric epoxidation of alpha,beta-unsaturated carboxylic acid derivatives with high enantioselectivity and broad substrate generality for the first time by changing the lanthanide metal and reaction conditions. Among them, catalytic asymmetric epoxidation of alpha,beta-unsaturated morpholinyl amides is quite useful in terms of synthetic utility of the corresponding alpha,beta-epoxy morpholinyl amides. Highly catalyst-controlled enantio- or diastereoselective epoxidation of the alpha,beta-unsaturated morpholinyl amides, coupled with diastereoselective reduction of beta-hydroxy ketones, enabled the synthesis of all possible stereoisomers of 1,3-polyol arrays with successful enantioselective total synthesis of several 1,3-polyol natural products, such as (-)-cryptocaryolone diacetate. In addition, the development of a new regioselective epoxide-opening reaction of alpha,beta-epoxy amides to the corresponding alpha- and beta-hydroxy amides enhanced the usefulness of the present epoxidation and was applied to the enantioselective total synthesis of (-)-fluoxetine. In the final section, I report the development of a new asymmetric two-center organocatalyst (TaDiAS) and its application to the enantioselective synthesis of aeruginosin 298-A and its analogues. Because of the remarkable structural diversity of TaDiAS, a practical asymmetric phase-transfer reaction with broad substrate generality was achieved. As a result, we succeeded in developing a highly versatile synthetic method for aeruginosin 298-A and its analogues. Inhibitory activity studies of the compounds against the serine protease trypsin provided preliminary information about their structure-activity relations.

Dibutyltin Dimethoxide‐Catalyzed Aldol Reaction of Enol Trichloroacetates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric aldol polymerization of bis(triethylsilyl enol ether) and dialdehyde

Mukaiyama aldol reaction smoothly occurred between bis(triethylsilyl enol ether) and dialdehyde in the presence of Lewis acid catalyst to yield polymers that consist of β-hydroxy carbonyl repeating units. When chirally modified Lewis acid catalyst was used, the optically active poly(β-hydroxy ketone)s were obtained by means of the asymmetric aldol polymerization.

Intermolecular aldol type reactions of phenacyl bromide with aldehydes mediated by active metallic indium in aqueous media

Mediated by active metallic indium generated in situ from metallic samarium and InCl3.4H2O, phenacyl bromide and aldehydes smoothly underwent intermolecular aldol type reaction in aqueous media affording β-hydroxy ketones in good yields and under mild conditions.

Composition of Reductive Cleavage Products of Cyclopenta[d]isoxazolines

The composition of the reductive cleavage products of cyclopenta[d]isoxazolines in acid medium depends on the acid, Raney nickel, and solvent used. Depending on the reaction conditions, we obtained β-hydroxy ketones, α,β-unsaturated ketones, or 2-acylcyclopentanes as the major products.

Enones of (+)‐ and (−)‐3‐pinanone: influence of chirality on flavour

AbstractStarting with (+)‐ and (−)‐3‐pinanone [(+)‐ and (−)‐2], the enones 3–12 were prepared by aldol condensation with various aldehydes. Without isolating the corresponding β‐hydroxy ketones, the target compounds 3–12 could be obtained in good to moderate yields directly from the starting bicyclic ketone. The odour properties of the enones were evaluated and described. It could be shown that the structure of the aldehyde as well as the chirality is crucial for the flavour impression of the enone. However, the (+)‐enantiomers generally possess more agreeable odours than their antipodes. Copyright © 2003 John Wiley & Sons, Ltd.

Dibutyltin dimethoxide-catalyzed aldol reaction of enol trichloroacetates

A catalytic aldol condensation of aldehydes with enol trichloroacetates was achieved using dibutyltin dimethoxide as a novel catalyst in a mixed solvent consisting of THF and MeOH. Various β-hydroxy ketones were diastereoselectively obtained in high yields up to 99%.

Total Synthesis of (‐)‐ and (+)‐Membrenone C.

A synthesis of the polypropionate marine defense substance (+)-membrenone C and its enantiomer that starts from (S)-2-methyl-3-(tert-butyldimethylsilyloxy)propanal is described. Key steps include (1) additions of chiral allenylmetal reagents to effect both chain homologation and the concomitant introduction of four stereo centers, (2) a bis-intramolecular hydrosilylation−oxidation sequence to install β-hydroxy ketone subunits, and (3) a bis-intramolecular aldol reaction to construct the two dihydropyrone termini.

Expeditious copper-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to alpha,beta-cycloalkenones and subsequent transformations.

Expeditious CuI-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to the five-, six-, seven-, and eight-membered alpha,beta-cycloalkenones is described. The reaction times are decreased dramatically compared to CuBr-(CH(3))(2)S catalysis. The resulting ketoacetals were subsequently cyclized to bicyclic beta-hydroxy ketones and alpha,beta-enones, followed by further transformations.

Convenient Methods for the Preparation of Unsymmetrical Double Aldols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies on the enzymatic kinetic resolution of β-hydroxy ketones

Kinetic resolution of aldol products using enzymatic transesterification and hydrolysis are described. The effect of structure of aldols on the enantioselectivity have also been studied in detail.

An enantioselective synthesis of the core unit of the non-nucleoside reverse transcriptase inhibitor taurospongin A

An enantioselective formal synthesis of taurospongin A has been achieved. The key steps involve chelation-controlled reductions of β-ketosulfoxide and β-hydroxy ketone intermediates and Sharpless asymmetric epoxidation to construct the tertiary alcohol stereoselectively.

Convenient Methods for the Preparation of Unsymmetrical Double Aldols

Abstract Double aldol reaction proceeded stereoselectively at one α-carbon of ketones to give α-(1-hydroxyalkyl)-β-hydroxyalkyl ketones (double aldols) in good to high yields by the following three methods: i) tin(II) trifluoromethanesulfonate-mediated aldol reaction of aldehydes with β-hydroxy ketones (mono-aldols) in the presence of tertiary amines, ii) samarium(II) iodide-mediated aldol reaction of aldehydes with alkyl or aryl oxiranyl ketones, iii) Sn(OTf)2-promoted aldol reaction of α-bromo ketones with aldehydes giving α-bromo-β-stannyloxy ketones which were then converted to titanium enolates on treatment with low-valent titanium. Double aldols were formed by subsequent reaction of the above titanium enolates with aldehydes in one-pot procedure. Further, small and medium-sized carbocyclic compounds whose ring skeletons were composed of double aldol structure were synthesized by SmI2-mediated intramolecular cyclization between oxiranyl ketone and aldehyde functions.

2-Ethyl-3-hydroxy-1-morpholinopyridin-4(1H)-one

The title compound, C11H16N2O3, crystallizes in the triclinic space group P\overline 1. The mol­ecules form dimers in the solid state, through hydrogen bonding involving the β-hydroxy ketone functionality.

2-Deoxy-2-iodo-β-glucopyranosyl Fluorides: Mild and Highly Stereoselective Glycosyl Donors for the Synthesis of 2-Deoxy-β-glycosides from β-Hydroxy Ketones

2-Deoxy-2-iodo-beta-glucopyranosyl fluoride 14 is a highly stereoselective glucopyranosyl donor that may be activated under mild conditions. Application of this new glycosyl donor to the glycosidation reactions of a variety of acceptors including beta-hydroxy ketones affords beta-glycosides with high efficiency and stereoselectivity. [reaction--see text]

Kinetic Resolution via Semipinacol Rearrangement of α‐Hydroxy Epoxides: A New Method for Asymmetric Synthesis of α‐Hydroxy Epoxides and β‐Hydroxy Ketones Containing an α‐Quaternary Carbon.

AbstractFor Abstract see ChemInform Abstract in Full Text.