Organocatalytic asymmetric total synthesis of (R)-rolipram and formal synthesis of (3S,4R)-paroxetine

An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.     

Practice and theory of enantioselective complexation gas chromatography

The practice and theory of enantioselective complexation GC is comprehensively reviewed for the first time. A multitude of racemic oxygen-, nitrogen- and sulfur-containing selectands can be separated without prior derivatization into enantiomers by complexation GC on optically active metal(II) bis[3-(perfluoroacyl)-(1R)-camphorate] selectors. Peak inversion is obtained when the selectors with opposite configuration are employed. Applications pertain to chiral analysis in asymmetric synthesis, enzymatic reactions, pheromone and flavour chemistry. Although the use of enantioselective complexation GC has diminished recently with the advent of modified cyclodextrins in enantioselective GC, the inherent principles of enantiorecognition together with other enantioselective phenomena can be elucidated easily by complexation GC. Using the concept of the retention-increment R' which allows the distinction between non-enantioselective and enantioselective contributions to retention, concise thermodynamic parameters of enantioselectivity - deltaD,L(deltaG) are accessible. The enantiomerization of configurationally labile enantiomers can be investigated and quantified by complexation GC. Four distinct enantioselective processes and four different coalescence phenomena have been discerned in complexation GC.     

Recent developments in enantioselective gold(I) catalysis

The use of gold(I) complexes as catalysts for organic transformations has become increasingly common over the past decade, leading to the development of a number of useful carbon-carbon and carbon-heteroatom bond-forming processes. In contrast, enantioselective catalysis employing gold(I) complexes was, until recently, exceedingly rare, due in large part to the pronounced tendency of gold(I) to form linear, two-coordinate complexes. However, new approaches and strategies have emerged over the past two years, leading to the development of a number of effective gold(I)-catalyzed enantioselective transformations, most notably the enantioselective hydrofunctionalization of allenes. Outlined herein is an overview of enantioselective gold(I) catalysis since 2005.     

Enantioselective syntheses of tremulenediol A and tremulenolide A

[reaction: see text] An enantioselective entry to the skeleton of the tremulane sesquiterpenes is described. The approach features a series of efficient transition metal-catalyzed reactions commencing with an enantioselective rhodium(II)-catalyzed intramolecular cyclopropanation followed by a regioselective allylic alkylation and a diastereoselective rhodium(I)-catalyzed [5 + 2] cycloaddition. This strategy was applied to the first enantioselective syntheses of tremulenediol A and tremulenolide A.     

Exploiting C3-symmetry in the dynamic coordination of a chiral trisoxazoline to copper(II): improved enantioselectivity, and catalyst stability in asymmetric lewis acid catalysis

Chiral C3-symmetric trisoxazolines are highly efficient stereodirecting ligands in enantioselective Cu(II) Lewis acid catalysis which is based on the concept of a stereoelectronic hemilability of the divalent copper; in direct comparison with the analogous bisoxazoline systems they are more efficient in the enantioselective alpha-amination as well as the enantioselective Mannich reaction of prochiral beta-ketoesters.     

Tetrazolic acid functionalized dihydroindol: rational design of a highly selective cyclopropanation organocatalyst

Herein we wish to report our development of an improved catalyst (S)-(-)-indoline-2-yl-1H-tetrazole (1) for the enantioselective organocatalyzed cyclopropanation of alpha,beta-unsaturated aldehydes with sulfur ylides. The new organocatalyst readily facilitates the enantioselective organocatalytic cyclopropanation, providing cyclized product in excellent diastereoselectivities ranging from 96% to 98% along with enantioselectivities exceeding 99% enantiomeric excess for all reacted alpha,beta-unsaturated aldehydes. The new catalyst provides the best results so far reported for intermolecular enantioselective organocatalyzed cyclopropanation.     

Synthesis of (-)-Vulcanolide by enantioselective protonation

Two efficient enantioselective syntheses of the more active (S,S)-enantiomer of the powerful musk odorant Vulcanolide are described. In both syntheses, the key step is an enantioselective protonation of a ketone enolate. A third enantioselective protonation, of a thiol ester enolate, was applied for the determination of the absolute configuration of Vulcanolide by comparison with a known compound.     

Water-tolerant enantioselective carbonyl-ene reactions with palladium(II) and platinum(II) Lewis acid catalysts bearing BINAP

Palladium(II) and platinum(II) Lewis acid catalysts bearing BINAP have been proved to be water-tolerant in enantioselective carbonyl-ene reactions, thus arylglyoxal monohydrate could be used directly as substrate achieving good to excellent enantioselectivities as high as 95.4% e.e.. The enantioselective carbonyl-ene reactions using phenylglyoxal monohydrate as substrate with four alkenes including methylenecyclohexane, 2,3-dimethyl-1-butene, 2,4,4-trimethyl-1-pentene and alpha-methylstyrene, were investigated demonstrating comparable or even higher yields and enantioselectivities in comparison with the corresponding carbonyl-ene reactions using dry phenylglyoxal as substrate for both palladium(II)-BINAP catalyst and platinum(II)-BINAP catalyst. The palladium(II) and platinum(II)-BINAP catalyzed enantioselective carbonyl-ene reactions between 4-methylphenylglyoxal monohydrate and the four alkenes were also investigated affording enantioselectivities between 76.2% and 91.8% e.e.. A mechanism involving the coordination of arylglyoxal and 2,2-dihydroxy-1-phenylethanone with chiral catalyst was proposed to interpret the enantioselective carbonyl-ene reactions using arylglyoxal monohydrate as substrate.     

Enantioselective borodeuteride reduction of aldimines catalyzed by cobalt complexes: preparation of optically active deuterated primary amines

[reaction: see text] The enantioselective borodeuteride reduction catalyzed by optically active beta-ketoiminato cobalt complexes was applied to N-(di(o-tolyl)phosphinyl)aldimines to afford the corresponding optically active deuterated primary amines in high yields with high enantiomeric excesses after simple deprotection. The present deuteride reduction of aldimines is in the opposite sense of the enantioselective for the previously reported borohydride reduction of ketones or diphenylphosphinyl aldimines. The stereochemical course in these enantioselective reductions is discussed.     

Highly enantioselective reaction of alpha-selenoorganolithium compounds with chiral bis(oxazoline)s and preparation of enantioenriched benzylidencyclohexanes

The enantioselective reaction of alpha-seleno carbanions derived from bis(phenylseleno)acetal and bis(2-pyridylseleno)acetal in the presence of bis(oxazoline)s with various electrophiles gave products with high enantioselectivity. The enantioselective reaction of alpha-lithio benzyl 2-pyridyl selenide gave the products with stereochemistry reverse to that obtained in the reaction of alpha-lithio benzyl phenyl selenide. Mechanistic investigation suggests the enantiodetermination of these reactions at -78 degrees C depends on dynamic thermodynamic resolution. The enantioselective reaction was applied to the preparation of enantioenriched olefins and epoxide.     

Enantioselective synthesis of (-)-pentalenene

A short, enantioselective synthesis of (-)-pentalenene is described. Catalytic enantioselective cyclopropenation with (R,R)-Rh2(OAc)(DPTI)3 was used to set the absolute stereochemistry, and an intramolecular Pauson-Khand reaction of the resulting cyclopropenyne was used to establish the quaternary center.     

A formal enantioselective acetate Mannich reaction: the nitro functional group as a traceless agent for activation and enantiocontrol in the synthesis of beta-amino acids

A two-step procedure involving the enantioselective addition of alpha-nitro esters to imines, followed by reductive denitration, provides a convenient new enantioselective synthesis of beta-amino acids. Specifically, beta-phenyl alanine derivatives with up to 98% ee are formed in good yield (64-88%) over two steps. The utility of the approach is demonstrated through the first enantioselective synthesis of the key beta-amino acid of (+)-chaenorhine.     

Enantioselective syntheses of 2-alkyl- and 2,6-dialkylpiperidine alkaloids: preparations of the hydrochlorides of (-)-coniine, (-)-solenopsin A, and (-)-dihydropinidine

[reaction: see text] Sequences of lithiation-substitution, enantioselective hydrogenation, and diastereoselective lithiation-substitution provide efficient highly enantioselective syntheses of 2-substituted and cis and trans 2,6-disubstituted piperidines. The methodology is demonstrated by syntheses of (-)-coniine, (-)-solenopsin A, and (-)-dihydropinidine as their hydrochlorides.     

Bifunctional catalyst promotes highly enantioselective bromolactonizations to generate stereogenic C-Br bonds

A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number of structurally distinct unsaturated acids. Like some known catalysts, this catalyst promotes highly enantioselective bromolactonizations of 4- and 5-aryl-4-pentenoic acids, but it also catalyzes the highly enantioselective bromolactonizations of 5-alkyl-4(Z)-pentenoic acids. These reactions represent the first catalytic bromolactonizations of alkyl-substituted olefinic acids that proceed via 5-exo mode cyclizations to give lactones in which new carbon-bromine bonds are formed at a stereogenic center with high enantioselectivity. We also disclose the first catalytic desymmetrization of a prochiral dienoic acid by enantioselective bromolactonization.     

Phosphoramidite gold(I)-catalyzed diastereo- and enantioselective synthesis of 3,4-substituted pyrrolidines

In this article the utility of phosphoramidite ligands in enantioselective Au(I) catalysis was explored in the development of highly diastereo- and enantioselective Au(I)-catalyzed cycloadditions of allenenes. A Au(I)-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective Au(I)-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (-)-isocynometrine.     

Enantioselective direct aminalization with primary carboxamides catalyzed by chiral ammonium 1,1'-binaphthyl-2,2'-disulfonates

A highly effective catalytic enantioselective direct aminal synthesis was developed. Chiral ammonium 1,1'-binaphthyl-2,2'-disulfonates, which were prepared in situ from (R)-BINSA and achiral amines, promoted the enantioselective addition of primary amides to aromatic aldimines.     

An enantioselective approach to (−)-platencin via catalytic asymmetric intramolecular cyclopropanation

This Letter describes an enantioselective approach to (−)-platencin. A uniquely functionalized chiral intermediate, which was prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) that we have developed, was successfully transformed to Nicolaou’s intermediate in his total synthesis of (−)-platencin.     

Enantioselective synthesis of spirooxoindoles via chiral auxiliary (bicyclic lactam) controlled SNAr reactions

A highly efficient enantioselective S(N)Ar reaction of chiral acyl bicyclic lactam with substituted-2,4-dinitrobenzenes was developed, affording products containing quarternary stereogenic centers. They are further utilized towards an enantioselective synthesis of spirooxoindoles.     

Enantioselective C−H Olefination of α‐Hydroxy and α‐Amino Phenylacetic Acids by Kinetic Resolution

Significant progress has been made in the past decade regarding the development of enantioselective C?H activation reactions by desymmetrization. However, the requirement for the presence of two chemically identical prochiral C?H bonds represents an inherent limitation in scope. Reported is the first example of kinetic resolution by a palladium(II)‐catalyzed enantioselective C?H activation and C?C bond formation, thus significantly expanding the scope of enantioselective C?H activation reactions.