Formal [4+2] cycloaddition reactions of N-sulfonyl-2,2-biindoles: synthesis of indolo[2,3-a]carbazoles and indigo azines

The formal [4+2] cycloaddition reactions of readily available N-sulfonyl-2,2^′-biindoles with various dienophiles is reported. The reaction with carbon-centered dienophiles leading to indolo[2,3-a]carbazoles is facilitated by the sulfonyl group, which is lost as part of the aromatization process. Reaction with aza-dienophiles gives access to indigo azines.     

Novel chiral 1-phosphono-1,3-butadiene for asymmetric hetero Diels-Alder cycloadditions with nitroso and azodicarboxylate dienophiles

Chiral 1-phosphonodienes bearing a bicyclic (R,R)-1,3,2-dioxaphospholane or a (R,R)-1,3,2-diazaphospholidine auxiliary are potent dienes for asymmetric hetero Diels-Alder reactions. Their reactivity towards model nitroso and azodicarboxylate dienophiles has been studied by means of theoretical chemistry at the B3LYP/6-31G∗∗ level. This model, taking solvent effects into account, allowed us to identify parameters governing the stereoselectivity of this reaction. Our study emphasizes a synergy effect when increasing the steric hindrance of substituents of both partners. This led us to predict high levels of diastereoselectivity for one diene. Accordingly, we have hereby illustrated a convenient and original synthesis of this diene and its cycloadditions with commercially available nitroso and azodicarboxylate dienophiles.     

Generation and cycloaddition reactions of indole-2,3-quinodimethanes

N-methyl and N-tert-butoxycarbonylindole-2,3-quinodimethanes ($\text{2}$ and $\text{3}$) have been generated and observed to undergo intermolecular cycloaddition reactions with dienophiles.     

A tandem decarboxylation and inverse electron-demand Diels-Alder reaction of amino-thiophenecarboxylic acids with 1,3,5-triazines

The scope of 1,3,5-triazine inverse electron-demand Diels-Alder (IDA) reactions was expanded to include aminothiophenecarboxylic acids as latent dienophiles. A series of 2-amino-3-thiophenecarboxylic acids (1a-d) and a 3-amino-2-thiophenecarboxylic acid (5) were introduced as productive dienophiles in IDA reactions with various 1,3,5-triazines (2a-e). This method is useful for the one-step synthesis of both thieno[2,3-d]pyrimidines and thieno[3,2-d]pyrimidines, which should complement existing methods.     

Research on the Solid State Fermentation of Jerusalem Artichoke Pomace for Producing <Emphasis Type="Italic">R</Emphasis>,<Emphasis Type="Italic">R</Emphasis>-2,3-Butanediol by <Emphasis Type="Italic">Paenibacillus polymyxa</Emphasis> ZJ-9

R,R-2,3-butanediol (R,R-2,3-BD) was produced by Paenibacillus polymyxa ZJ-9, which was capable of utilizing inulin without previous hydrolysis. The Jerusalem artichoke pomace (JAP) derived from the conversion of Jerusalem artichoke powder into inulin extract, which was usually used for biorefinery by submerged fermentation (SMF), was utilized in solid state fermentation (SSF) to produce R,R-2,3-BD. In this study, the fermentation parameters of SSF were optimized and determined in flasks. A novel bioreactor was designed and assembled for the laboratory scale-up of SSF, with a maximum yield of R,R-2,3-BD (67.90 g/kg (JAP)). This result is a 36.3% improvement compared with the flasks. Based on the same bath of Jerusalem artichoke powder, the total output of R,R-2,3-BD increased by 38.8% for the SSF of JAP combined with the SMF of inulin extraction. Overall, the utilization of JAP for R,R-2,3-BD production was beneficial to the comprehensive utilization of Jerusalem artichoke tuber.     

Novel rearrangement of 1H-2,3-benzoxazines to cyclic N-acyl hemiaminals: application to the synthesis of 1-arylnaphthalene skeletal congeners

The rearrangement of 1H-2,3-benzoxazine derivatives has been investigated. The reaction affords cyclic hemiaminal derivatives for their conversion to the corresponding 1-arylisobenzofurans, which can be trapped by various dienophiles to afford skeletal congeners of 1-arylnaphthalene lignans.     

Asymmetric Diels–Alder reactions of optically active oxazolidinone-derived vinylsulfonamides

Chiral vinylsulfonamides bearing an oxazolidin-2-one moiety derived from (R)-2-phenylglycinol and (1R,2S)-norephedrine have been employed as dienophiles in asymmetric Diels–Alder reactions at normal pressure affording d.e.s of up to 99% when EtAlCl₂ or Et₂AlCl were employed as Lewis acids. Theoretical calculations justify the observed enantio- and diastereoselectivity.     

Asymmetric hydrogenation of (E)-α,β-bis(N-acylamino)acrylates catalyzed by a rhodium complex with trans-chelating chiral diphosphine ligand

The asymmetric hydrogenation of (E)-α,β-bis(N-acylamino)acrylates was promoted by a rhodium complex bearing a trans-chelating chiral diphosphine ligand (R,R)-(S,S)-PrTRAP, providing the corresponding optically active (2S,3R)-2,3-bis(N-acylamino)carboxylates with 79–82% ee. The 2,3-bis(N-acylamino)carboxylates isolated were readily hydrolyzed under acid to afford (2S,3R)-2,3-diaminocarboxylic acids in 95% yield without epimerization.     

Synthesis of tricyclic isoindoles and thiazolo[3,2-c][1,3]benzoxazines

The thermolysis of (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylic acids in Ac₂O led to novel 3-methylene-2,5-dioxo-3H,9bH-oxazolo[2,3-a]isoindoles and chiral (9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindoles were obtained on FVP. Starting from l-cysteine methyl ester (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazines were obtained as single stereoisomers. The thermolysis of (3R,10bR)-5-oxo-2,3-dihydro-10bH-[1.3]thiazolo[3,2-c][1,3]benzoxazine-3-carboxylic acid in Ac₂O gave 5-acetyl-2-phenyl-2,3-dihydrothiazole. The structures of methyl (3R,9bS)-5-oxo-2,3,5,9b-tetrahydrothiazolo[2,3-a]isoindole-3-carboxylate 1a and methyl (2R,4R)-N-chlorocarbonyl-2-(2-hydroxyphenyl)thiazolidine-4-carboxylate 9 were determined by X-ray crystallography.     

A simple and practical access to enantiopure 2,3-diamino acid derivatives

Enantiomerically pure (4R,5R)- and (4S,5S)-2-imidazolines 5 were conveniently obtained on a gram scale. These can be converted into enantiopure (2R,3R)-2,3-diamino ester 6 or 2,3-diamino alcohol 7 by hydrolysis or reduction.     

Stereoselective reduction of 2-butenolides to chiral butanolides by reductases from cultured cells of Glycine max

The stereoselective reduction of 2-butenolides by two reductases, p51 and p83, from cultured plant cells of Glycine max was investigated. The reduction of 2-methyl-2-butenolide by p51 reductase produced (R)-2-methylbutanolide, whereas the reduction by p83 reductase gave (S)-2-methylbutanolide. Both reductases reduced 3-methyl-2-butenolide to (R)-3-methylbutanolide. The reduction of 2,3-dimethyl-2-butenolide by p51 reductase gave (2R,3R)-2,3-dimethylbutanolide, whereas the reduction by p83 reductase produced (2S,3R)-2,3-dimethylbutanolide. The reduction of 4-alkyl-2-butenolides with these reductases was accompanied by resolution of chiral centers affording (R)-4-alkylbutanolides.     

Asymmetric Diels–Alder and ene reactions promoted by a Ti(IV) complex bearing a C2-symmetric tridentate ligand

A new Ti(IV) complex obtained from the C₂-symmetric amino diol (1R,5R)-3-aza-3-benzyl-1,5-diphenyl pentan-1,5-diol, (1R,5R)-1, is used effectively as a Lewis acid promoter in asymmetric Diels–Alder reactions. Using various Evans' oxazolidinones as dienophiles and cyclopentadiene as the diene high yields of the adducts with moderate enantioselectivity, under different reaction conditions are achieved. The effects of solvent, temperature and ligand on the enantioselectivity of the Diels–Alder products are reported. Molecular modelling studies provide an understanding of the diastereofacial selectivity of the Diels–Alder reactions. Asymmetric carbonyl-ene reactions between various glyoxylate esters and α-methyl styrene are also described.     

Enantioselective acylation of 2-hydroxymethyl-2,3-dihydrobenzofurans catalysed by lipase from Pseudomonas cepacia (Amano PS) and total stereoselective synthesis of (−)-(R)-MEM-protected arthrographol

Lipase Amano PS catalysed acylation of (±)-2-hydroxymethyl-2,3-dihydrobenzofurans using vinyl acetate as the acyl donor in n-hexane gave (−)-(R)-2-acetoxymethyl-2,3-dihydrobenzofurans and (+)-(S)-2-hydroxymethyl-2,3-dihydrobenzofurans in high enantiomeric excess. (−)-(R)-Acetate 18j is converted to (−)-(R)-MEM-protected arthrographol 22.     

A novel,high-yielding approach to a chiral inducer: (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol

A new method for preparing (2R,3R)-1,4-dimethoxy-1,1,4,4-tetraphenylbutane-2,3-diol in high yield based on selective 2,3-spiroboration of (2R,3R)-1,1,4,4-tetraphenylbutanetetraol has been developed. It avoids traditional oxidation and reduction steps, and provides a simplified, more straightforward, and high-yielding synthesis of the title compound.     

Direct regio- and stereoselective synthesis of squalene 2,3;22,23-dioxide using dioxiranes

Dimethyldioxirane (1a) and its trifluoro analog (1b) were employed to achieve selectively the direct transformation of squalene 2,3(S)-oxide and of squalene 2,3(R)-oxide into the corresponding 2,3(S);22(S),23-dioxide and 2,3(R);22(R),23-dioxide, respectively. These transformations were found to occur with convenient regio- and diastereoselectivity, providing easy access to the valuable dioxides metabolites. The powerful methyl(trifluoromethyl)dioxirane (1b) is the reagent of choice to achieve optimum yields of the target compounds.     

Asymmetric [4+2] cycloadditions employing 1,3-dienes derived from (R)-4-t-butyldimethyl-silyloxy-2-cyclohexen-1-one

1,3-Dienes derived from (R)-4-t-butyldimethylsilyloxy-2-cyclohexen-1-one react with activated dienophiles to form predominately (or sometimes exclusively) syn/endo products. These controlled [4+2] cycloadditions increase the asymmetric complexity from one asymmetric center in the starting material to five asymmetric centers in the products in a single step, and provide a powerful approach for the asymmetric synthesis of compounds containing the bicyclo[2.2.2]octanone carbon skeleton.     

Asymmetric hydrogenation of the C–C double bond of 1- and 1,2-methylated maleimides with cultured suspension cells of Marchantia polymorpha

Suspension cultured cells of Marchantia polymorpha have the potential to hydrogenate the C–C double bonds of 2-methyl- and 2,3-dimethylmaleimide derivatives to give enantiomerically pure (2R)-2-methyl- and (2R,3R)-2,3-dimethylsuccinimide derivatives, respectively.     

New approach to the enantiomerically pure 1,2,3-trihydroxypropylphosphonates

The replacement of 2,3-O-cyclohexylidene-d-glyceraldehyde with (2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxane-2-carbaldehyde (Ley’s aldehyde) has led to significant improvements in the isolation of both diastereoisomers of the respective 2,3-O-BDA 1,2,3-trihydroxypropylphosphonates. The triethylamine-catalysed addition of dialkyl phosphites and lithium diethyl phosphonate gave the products in moderate (ca. 1:2) diastereoselectivity while the application of diethyl trimethylsilyl phosphite afforded a 1:9 mixture of diethyl (R)- and (S)-hydroxy-[(2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxan-2-yl]methylphosphonates.     

Enantiomerically pure 4-amino-1,2,3-trihydroxybutylphosphonic acids

(1S,2R,3S)-, (1R,2R,3S)- and (1S,2R,3R)-4-amino-1,2,3-trihydroxybutylphosphonic acids were synthesised. The synthetic strategy involved preparation of the respective 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose, addition of dialkyl phosphites, separation of C-1 epimeric O,O-dibenzyl phosphonates, the reduction of azides and the removal of the protecting groups. The (2R,3S) and (2R,3R) configurations in the final products were secured by employing diethyl l-tartrate and d-isoascorbic acid as starting materials. The stereochemical course of the addition to the carbonyl groups in 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose followed that established earlier for 2,3-O-isopropylidene-d-glyceraldehyde and similar (3:1-4:1) diastereoselectivities were achieved.     

Stereoselective synthesis of 3-deoxy-piperidine iminosugars from l-lysine

A new method using electrochemical oxidation and/or OsO₄ oxidation has been used for the stereoselective synthesis of 2,3,6-trihydroxylated (5S)-piperidine derivatives. The electrochemical method was successively used for the conversion of N-protected piperidines to N-protected 1-methoxypiperidines and for the conversion of 2,3-didehydro-1-methoxypiperidine derivatives to 2,3-trans-1,2,3-triacetoxypiperidine derivatives. These triacetates were easily transformed into (2S,3S)-6-triacetoxy-(5S)-methylpiperidine and (2R,3R)-6-triacetoxy-(5S)-methylpiperidine. In addition, the 2,3-cis-dihydroxylation of 2,3-didehydro-1-methoxypiperidine derivatives with OsO₄ afforded (2R,3S)-6-triacetoxy-(5S)-methylpiperidine and (2S,3R)-6-triacetoxy-(5S)-methylpiperidine.