Secondary Carbinols Research Articles

Aldol Reactions of Axially Chiral 5-Methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones.

Axially chiral 5-methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones have been subjected to aldol reactions with benzaldehyde to produce secondary carbinols which have been found to be separable by HPLC on a chiral stationary phase. Based on the reaction done on a single enantiomer resolved via a chromatographic separation from a racemic mixture of 5-methyl-2-(α-naphthyl)imino-3-(α-naphthyl)-thiazolidine-4-one by HPLC on a chiral stationary phase, the aldol reaction was shown to proceed via an enolate intermediate. The axially chiral enolate of the thiazolidine-4-one was found to shield one face of the heterocyclic ring rendering face selectivity with respect to the enolate. The selectivities observed at C-5 of the ring varied from none to 11.5:1 depending on the size of the ortho substituent. Although the aldol reaction proceeded with a lack of face selectivity with respect to benzaldehyde, recrystallization returned highly diastereomerically enriched products.

Kinetic Resolution of Secondary Carbinols by a Chiral N,N-4-Dimethylaminopyridine Derivative Containing a 1,1′-Binaphthyl Unit: Hydrogen Bonding Affects Catalytic Activity and Enantioselectivity

Abstract We developed an acylative kinetic resolution of secondary carbinols using a binaphthyl-based N,N-4-dimethylaminopyridine (DMAP) derivative 1d with tert-alcohol substituents. The reaction proceeded with a wide range of carbinols with moderate to high selectivity (s) (up to s = 79.5). Kinetic studies revealed that catalyst 1d was more catalytically active than the corresponding bis-methyl ether 1d′ or DMAP. Hydrogen bonding between tert-alcohols of the catalyst and secondary carbinols was responsible for the enhanced reaction rate and high enantioselectivity.

Synthesis of new ( R)-secondary carbinols with different structures via enzymatic resolution

The present study deals with the biocatalytic enantioselective synthesis of 19 new chiral alcohols with alkyl (C 11–C 19) and phenyl, substituted phenyl, heteroaromatic, and naphthyl groups 4a– 4z with an ( R)-configuration and high enantiomeric excess (∼100%). The corresponding ketones 1a– 1z were synthesized and then reduced with NaBH 4 to their racemic alcohols 2a– 2z, which were converted into their racemic acetyl derivatives 3a– 3z. Enzymes of four different types were used for the enantioselective hydrolysis of these acetyl compounds 3a– 3z. The optimal reaction conditions for these four enzymes were established by investigating the enantiomeric excesses by chiral HPLC. Amano lipase from Burkholderica cepacia ( Pseudomonas cepacia) AL-PS was determined as the best enzyme in this work. This study presents an environmentally friendly and green chemistry method for the synthesis of these new ( R)-chiral carbinols 4a– 4z.

ChemInform Abstract: Lipase-Mediated Optical Resolution of Bicyclic Secondary Carbinols.

Abstract The optical resolution (±) -endo-bicyclo[2.2.1] heptan-2.ol and (±) bicyclo [2.2.2] octan-2-ol proceeds by porcine lipase catalyzed transesterification under anhydrous conditions.

ChemInform Abstract: Remarkably Effective and Simple Syntheses of Enantiomerically Pure Secondary Carbinols from Achiral Ketones.

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Synthesis and kinetic resolution of furyl substituted secondary carbinols by porcine pancreatic lipase under solvent free conditions

Chiral furyl substituted carbinols were prepared from the related carbonyl compounds and their enzymatic kinetic resolution was studied by using porcine pancreatic lipase (PPL) in transesterification reaction under solvent free condition. This study revealed that carbinols having one less bulky group on the chiral center are good substrates for PPL and the resolution proceeds with higher ee,s and less reaction time.

Microwave‐Assisted Oxidation of Alcohols with N,N,N′,N′‐Tetrabromobenzene‐1,3‐Disulfonamide and Poly(N‐Bromobenzene‐1,3‐Disulfonamide) under Solvent‐Free Conditions

AbstractAn efficient and mild methodology for the oxidation of primary and secondary alcohols to the corresponding carbonyl functions is described with N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonamide and poly(N‐bromobenzene‐1,3‐disulfonamide) using microwave irradiation under solvent‐free conditions. Aliphatic, benzylic and allylic alcohols are rapidly oxidized without over‐oxidation to carboxylic acids. Secondary carbinols are slowly oxidized so that the reaction is highly chemoselective.

The Meyer—Schuster Rearrangement of Ethoxyalkynyl Carbinols.

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Reduction of π‐Deficient Heterocyclic Secondary Carbinols with Sodium Borohydride/Trifluoroacetic Acid

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A Simple One‐Pot Organometallic Formylation/Trapping Sequence Using N‐Formylcarbazole.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Simple One-pot Organometallic Formylation/Trapping Sequence UsingN-Formylcarbazole

Treatment of a range of sp3-, sp2- and sp-nucleophiles, such as various organolithium compds. and Grignard reagents, with N-formyl carbazole leads to the formation of the metastable anionic carbazole carbinols. In the presence of a second nucleophilic reagent, such as phosphonoacetate or an organolithium compd., these intermediates collapse on warming to the aldehyde which is trapped in situ to afford the a,b-unsatd. esters or secondary carbinols, resp. [on SciFinder (R)]

A Very Mild and Chemoselective Oxidation of Alcohols to Carbonyl Compounds

Efficient oxidation of primary alcohols and beta-amino alcohols to the corresponding aldehydes and alpha-amino aldehydes can be carried out at room temperature and in methylene chloride, using trichloroisocyanuric acid in the presence of catalytic TEMPO: aliphatic, benzylic, and allylic alcohols, and beta-amino alcohols are rapidly oxidized without no overoxidation to carboxylic acids. Secondary carbinols are slowly oxidized so that the reaction is highly chemoselective. Reaction: see text.

A novel chiral synthetic equivalent of glyoxal and its application to the asymmetric synthesis of O-protected α-hydroxy aldehydes

Diastereomerically pure 2-formyl-N-Boc-1,3-oxazolidine 7 was prepared in 83% yield from stannyloxazolidine 4. Grignard additions to the formyl group of compound 7 in the presence of Lewis acids afforded diastereomerically pure secondary carbinols 8. Protection of the hydroxyl group and unmasking of the oxazolidine ring gave O-protected α-hydroxy aldehydes 11, which were immediately reduced to the corresponding 1,2-diols 12.

(R)-Trifluoro- and Difluoropyruvaldehyde N,S-Ketals: Chiral Synthetic Equivalents of beta-Trifluoro and beta-Difluoro alpha-Amino Aldehydes.

A new, efficient, and stereoselective two-step approach to stereochemically defined chiral nonracemic gamma-tri- and gamma-difluoro beta-amino alcohols (70% to >95% ee) is described, using tri- and difluoropyruvaldehyde N,S-ketals (R)-1a,b as starting materials. Addition of Grignard reagents to (R)-1 occurs with moderate to excellent anti-stereocontrol, depending on the nature of the organomagnesium halides, providing the beta-p-tolylthio beta-benzyloxycarbonylamino secondary carbinols 5. The stereochemical outcome of these reactions can be rationalized by means of a chelated Cram's cyclic model, where the NCbz group is the chelating ligand and the p-tolylthio residue acts as the stereocontrolling "large" group. Reductive displacement of the 2-p-tolylthio substituent of 5 efficiently takes places by means of the NaBH(4)/pyridine system, probably via the corresponding intermediate transient imines 13, providing sulfur-free gamma-tri- and gamma-difluorinated beta-amino alcohols 7 with high levels of anti-stereoselectivity. A considerable shift toward syn-stereoselectivity was obtained performing the reaction on the corresponding phenylacetates 8. Cleavage and reduction of the NHCbz moiety of 7 provided tri- and difluoro analogues of, respectively, norephedrine (11) and ephedrine (12).

N-Cbz-Trifluoropyruvaldehyde N, S-ketal: Absolute stereochemistry and addition of Grignard reagents. Highly stereoselective entry to trifluoro analogues of Ephedra alkaloids

The chiral non racemic N-Cbz-trifluoropyruvaldehyde- N, S-ketal 1a (enantiomeric excess up to 74%) is a new trifluoro 3-C building block, which has been reacted with several Grignard reagents, stereoselectively affording the corresponding secondary carbinols 2. The N, S-ketal stereocentre, whose absolute stereochemistry has been determined by X-ray analysis of the α-phenylpropionate 3, is able to provide excellent stereocontrol. Highly stereoselective p-tolylthio group displacement afforded the N-Cbz-phenyl derivative 2d, transformed into trifluoro-norephedrine (S,S)- 5 and -ephedrine (S,S)- 6 .

Chemoenzymatic synthesis of enantiomers of a new retinoid to investigate the role of chirality in the biological response

We have prepared both enantiomers of a new retinoid ( IIa and IIb) partly by using lipase resolution of 1-acetoxy-1-(5, 6, 7, 8 - tetrahydro - 5, 5, 8, 8-tetramethyl-2-naphthyl) ethane. Absolute configuration of resulting secondary carbinols ( 4a and 4b) was assigned using lanthanide induced shifts NMR experiments on MTPA esters of 4a and 4b. Only the enantiomer (R-(−)- IIa) is active on the differentiation of F9 embryonal teratocarcinoma cells (F9 cells).

1,3-asymmetric induction in the reduction ofα-alkyl β-Ketosulfoxides with DIBAL/ZnBr 2

The highly stereoselective reduction of chiral α-alkyl β-ketosulfoxides with DIBAL/ZnBr 2 is governed by the configuration at the sulfur (1,3-induction) and not by that of the C-α (1,2-induction) as it has been previously reported. This fact considerably increases the scope of the Solladié's methodology to synthesize optically pure secondary carbinols. Those substituents decreasing the capability of the carbonyl oxygen to chelate the ZnBr 2 induce a decrease in the stereoselectivity.

Lipase mediated optical resolution of bicyclic secondary carbinols

The optical resolution (±) -endo-bicyclo[2.2.1] heptan-2.ol and (±) bicyclo [2.2.2] octan-2-ol proceeds by porcine lipase catalyzed transesterification under anhydrous conditions.

Remarkably effective and simple syntheses of enantiomerically pure secondary carbinols from achiral ketones

The chiral oxazaborolidine ( 1)-catalyzed reduction of the ketones 2, 6 and 8 has provided simple access to the chiral secondary carbinols 3, 7, and 9 in very high enantiomeric purity.

Formolysis and acetolysis of linear saturated and allylic secondary cyclopropyl carbinols

Simple esterification of a series of secondary aliphatic cyclopropyl carbinols under the influence of concentrated HCO2H or AcOH without modification of the carbon skeleton is disclosed. Under the same conditions related allyl alcohols undergo stereospecific isomerization to the corresponding esters of 3E,5E-dienols.