Synthesis of threo-β-aminoalcohols from aminoaldehydes via chelation-controlled additions. Total synthesis of l-threo sphingosine and safingol

Chelation-controlled addition of organocuprates to N-carbamoyl aminoaldehydes, prepared from functionalized amino acids, generated predominately the threo-β-amino alcohol derivatives through chelation with the carbamoyl moiety. The carbamate group is a stronger chelating group than other potentially good chelators, for example ethers, esters, thioethers, and gives good diastereoselectivity with cuprates. Thus addition of lithium divinylcuprate to the aldehyde generated from the serine derivative 25 in the presence of extra copper for chelation afforded the threo compound 26 in 83% yield. Cross-metathesis and cleavage of the protecting groups furnished l-threo sphingosine 21. In addition the lyso-sphingolipid protein kinase C inhibitor, safingol, 22, was prepared from commercially available O-benzyl N-BOC serine 28 in six steps and 56% overall yield by this method.     

Rate and Stereoselectivity Changes During Hydrogenation of n-Heterocycles

High diastereoselectivities were obtained in the heterogeneous catalytic hydrogenation of chiral pyrrole and pyridine derivatives with complete conversion, in non-acidic medium. The products of the hydrogenations, secondary and tertiary amines act as catalyst modifiers, increasing the d.e. values in the last period of the reactions.     

Synthesis and Stereochemistry of Novel Dibrominated 1,5-Dioxaspiro[5.5]undecane Derivatives

Summary.  The synthesis and stereochemistry of new dibrominated spiro-1,3-dioxane derivatives are reported. Investigations by means of NMR methods and single crystal X-ray diffraction for two compounds revealed the high regio- and diastereoselectivity of the bromination reaction of some new spiro-1,3-dioxanes and the asymmetric induction of the chiral carbon atom located in the spiro skeleton. Received July 13, 1999. Accepted October 21, 1999     

Copper(I)-catalyzed diastereoselective formation of oxazolines and N-sulfonyl-2-imidazolines

A simple and short method for the reaction of methyl isocyanoacetate with aldehydes and N-sulfonylimines is presented. The reaction is catalyzed by copper(I) complexes and proceeds with excellent yields and high diastereoselectivities.     

Studies in stereoselective [2+2]-cycloadditions with dichloroketene

During the investigation of the reaction of dichloroketene with cyclic enoxy-lactones and acyclic enoxy-ester substrates it was found that only the acylic variants effectively participated in the [2+2]-cycloaddition. Although a complete understanding of the reasons for this are lacking, molecular mechanics calculations do suggest that an out of plane twist of the cabonyl group in the acyclic compounds may be partially responsible. After screening a variety of chiral auxiliaries it was found that useful levels of diastereoselectivity (2.6-10.8:1) could be obtained in this cycloaddition reaction when (R)-2,2-diphenylcyclopentanol was used as the chiral auxiliary.     

Preparation of enantiomerically pure 5,6-dihydroxy-isobenzofuranones and 5,6-dihydroxy-4,7-methano-isobenzofuranones

Summary Optically pure available lactones1 and5 were diastereoselectively oxidised tocis-diols2 and6 by KMnO₄ and to epoxides3 and7 by 3-chloroperoxybenzoic acid. Epoxide3 was cleaved totrans-diol4, whereas hydrolysis of7 afforded tricyclic carboxylic acid8. Optic ally puredihydroxylactones2,4, and6 are valuable models for structure determination of the antimicrobial garlic component garlicin.

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Synthese enantiomerenreiner 5,6-Dihydroxy-isobenzofuranone und 5,6-Dihydroxy-4,7-methano-isobenzofuranone

Zusammenfassung Die in enatiomerenreiner Form verfügbaren Lactone1 und5 wurden durch diastereoselektive Oxidation mit KMnO₄ zu dencis-Diolen2 und6 bzw. mit 3-Chlorperoxybenzoesäure zu den Epoxiden3 und7 umgesetzt. Das Epoxid3 liefert bei der Hydrolyse dastrans-Diol4, während aus7 die tricyclische Carbonsäure8 entsteht. Die optisch reinen Dihydroxylactone2,4 und6 können als Vergleichssubstanzen zur Strukturaufklärung des antimikrobiellen Knoblauchinhaltsstoffes Garlicin dienen.

     

2-(Arylsulfinylmethyl)oxazinanes: chiral carbonyl equivalents. Application to the asymmetric synthesis of 1,2,3,4-tetrahydro-β-carbolines

2-(p-Tolylsulfinylmethyl)oxazinane, a chiral carbonyl equivalent, has been synthesised and used for the diastereoselective synthesis of tetrahydro-β-carbolines including intermediates of yohimbine and herman alkaloids. A fair degree of diastereoselectivity, comparable with other approaches, has been achieved.     

Asymmetric synthesis of spiro 2-pyrrolidin-5-ones, 2-piperidin-6-ones and 1-isoindolin-3-ones. Part 1: N-Acyliminium ion cyclisations with an internal arene nucleophile

A series of chiral non-racemic 5,5- and 5,6-bicyclic lactams is prepared from (R)-phenylglycinol. These are isomerised on treatment with aluminium trichloride in 1,2-dichloroethane to give spiro lactams in high yield and >3:1 diastereoselectivity. From four structures determined by X-ray crystallography, it follows that spiro indenes are formed preferentially with retention of configuration at the spiro carbon atom and spiro naphthalenes with inversion.     

Acetate aldol reactions of chiral oxocarbenium ions

Chiral oxocarbenium ions have been exploited to carry out highly diastereoselective and enantioselective acetate aldol addition reactions. The chiral auxiliary has been optimized to give the product with good diastereoselectivity.     

Diastereoselective formation of cyclochiral amino acids-substituted resorcin[4]arenes

The Mannich reaction between selectively tetratosylated resorcin[4]arene, formaldehyde and (S)-phenylalanine (or (S)-phenylglycine) methylamide gave cyclochiral mono- or dibenzoxazines with high diastereoselection as revealed by NMR and X-ray structural studies. X-ray structures of the products show the variety of intramolecular interactions that can be responsible for the diastereoselection of this acid-catalyzed reaction.