Steroids as chiral model compounds for selective reactions with metals

Our own work on steroid compounds with defined conformation as chiral model compounds for investigations of chemo-, regio- and stereoselectivity of metal-mediated new reactions is reviewed. Reactions with nickelacycles, (π-allyl)zirconoxycarbene complexes, iron tricarbonyl complexes of dienes and 1-azadienes, the Ru-catalyzed synthesis of 1,3-dihydropyrrol-2-ones from 1-azadienes, the Pd-catalyzed cyclopropanation of 1-azadienes, syntheses with cuprio steroids, copper complexes of amino alcohol derivatives and the copper-mediated hydroxylation of nonactivated C-H bonds with molecular oxygen are discussed.     

Stereoselective preparation of chiral compounds in Mannich-type reactions of a bicyclic imine and phenols or indole

Mannich-type reactions of a chiral bicyclic imine and various nucleophiles yield the corresponding adducts with good to high diastereoselectivity. The influence of the reaction conditions on the yield and stereochemical outcome is investigated. The configuration of the products is established by ¹H NMR spectroscopy, and the major isomers of two adducts are characterized by X-ray crystallography.     

Stereoselective reactions of chiral enolates. Application to the synthesis of (+)-prelog-djerassi lactonic acid.

The application of chiral metal enolates 3 and 4 have been employed in an efficient synthesis of (+)-Prelog-Djerassi lactone (1).     

Stereoselective reactions of trivalent phosphorus compounds

The data on stereoselective reactions of achiral compounds of trivalent phosphorus with chiral nucleophiles (derivatives of secondary alcohols, amines, and amino acids) are analyzed and discussed. In certain cases, these reactions enable preparation of optically active aminophosphines and phosphinites, precursors in the synthesis of chiral organophosphorus compounds and phosphine ligands. The reactions are suitable for elucidation of mechanism and stereochemistry of nucleophilic substitution at trivalent phosphorus atom.     

Stereoselective aza-Darzens reactions of tert-butanesulfinimines: convenient access to chiral aziridines

Stereoselective synthesis of 2,3-di- and 2,2',3-tri-substituted aziridines in good yields and excellent diastereoselectivities are achieved through aza-Darzens reactions of a range of tert-butanesulfinyl aldimines and ketimines with ethyl bromoacetate.     

Nitrone cycloadditions to 1,2-diphenylcyclopropenes and subsequent transformations of the isoxazolidine cycloadducts

1,3-Dipolar cycloaddition of C-aryl,N-aryl (or N-methyl) nitrones with a number of 1,2-diphenylcyclopropenes substituted at the C(3) position occurs with the formation of expected "normal" cycloadducts (with N-methylnitrones) and products of their subsequent transformations. Among them are corresponding alpha-acetophenyl aziridines and tetra (or penta) -arylpyrroles. Aziridines and the normal cycloadducts can be also thermally converted to such arylpyrroles with moderate to good yields. Substitution at the C(3( position of cyclopropenes by an electron acceptor group decreases the reactivity of cyclopropenes.     

Stereoselective synthesis of phosphinite complexes new route to chiral phosphines

Consecutive substitutions of chlorine in dichlorophenylphosphine by lithium cinchoninate and arylcyanocuprates lead stereoselectively to the corresponding $\text{R}$ P^III esters ; the latter are converted, by methyllithium, into chiral phosphines.     

Stereoselective pinacol coupling of chiral formylferrocene using divalent samarium triflate: preparation of a new chiral bisferrocenyl oxazoline ligand and its application to asymmetric Diels-Alder reactions

[reaction: see text] The pinacol coupling reaction of planar chiral ortho-oxazoline-substituted formylferrocene was smoothly mediated by SmI2 or Sm(OTf)3 to give the (R,R) isomer selectivity (up to 76% diastereomeric excess). The combination of Yb(OTf)3 and the (R,R)-ferrocenyl diol was revealed to be a good catalyst for the asymmetric Diels-Alder reaction of 3-acyloxazolidinone with cyclopentadiene, and the endo adduct was produced in up to 80% enantiomeric excess.     

Stereoselective 1,3-dipolar cycloadditions of a chiral nitrone derived from erythrulose. An experimental and DFT theoretical study

We have investigated several 1,3-dipolar cycloadditions of a chiral nitrone prepared from L-erythrulose. While cycloadditions to carbon-carbon multiple bonds of dipolarophiles such as ethyl acrylate, ethyl propiolate, or dimethyl acetylenedicarboxylate were poorly stereoselective, reaction with acrylonitrile provided predominantly one diastereomeric adduct. Furthermore, the regioselectivity exhibited by the two structurally similar dipolarophiles ethyl acrylate and ethyl propiolate was found to be opposite. The molecular mechanisms of these cycloadditions have thus been investigated by means of density functional theory (DFT) methods with the B3LYP functional and the 6-31G and 6-31+G basis sets. A simplified achiral version of nitrone 1 as the dipole, and methyl propiolate or acrylonitrile as the dipolarophiles, were chosen as computational models. The cycloadditions have been shown to take place through one-step pathways in which the C-C and C-O sigma bonds are formed in a nonsynchronous way. For the reaction with methyl propiolate, DFT calculations predict the experimentally observed meta regioselectivity. For the reaction with acrylonitrile, however, the predicted regioselectivity has been found to depend on the computational level used. The calculations further indicate the exo approach to be energetically favored in the case of the latter dipolarophile, in agreement with experimental findings. The main reason for this is the steric repulsion between the nitrile function and one of the methyl groups on the nitrone that progressively develops in the alternative endo approach.     

Ring closing and opening reactions leading to aza-polycyclic aromatic compounds

A series of functionalized aza-polycyclic aromatic compounds were prepared by a superacid-promoted ring closing and opening reaction cascade. A reaction mechanism is proposed, which involves reactive dicationic intermediates. A key step in the conversions involves ipso protonation of an aryl group and elimination of an alkyl phenyl group.     

Stereoselective synthesis of a new chiral synthon: a cyclic pseudodipeptide containing an aspartic acid derivative and l-valine

A simple stereoselective synthesis of cyclic synthons 4a,b and 10a,b, derived from an l-valine unit and an unnatural derivative of the aspartic acid, has been accomplished starting from the chiral synthon 1 and following the procedure already reported by us for the synthesis of similar compounds. These cyclic synthons are interesting substrates because they can behave as both electrophiles and nucleophiles and could be useful starting materials for the preparation of higher peptides such as, for instance, the unnatural tetrapeptides 15 and 18, through the condensation of 4a with 6a or 13 with 17, respectively.     

Stereoselective preparation and reactions of configurationally defined dialkylzinc compounds

The reaction of cyclic and open-chain diastereomerically pure secondary organoboranes with diisopropylzinc allows the preparation of secondary dialkylzinc reagents with good to excellent retention of configuration as shown by deuterolysis and CuI- and Pd0-mediated reactions with electrophiles. The importance of a high boron-zinc exchange rate to obtain high diastereoselectivity has been shown. Improvement of the configurational stability and stereomeric purity of the zinc intermediates has been obtained by using mono-isopinocampheylborane ((-)-IpcBH2) providing optically active dialkylzinc compounds (up to 96% ee) with enhanced diastereoselectivities.     

Hydrazine-1-carbonitriles: new synthesis approach to and reactions with carbonyl compounds

Abstract  

A series of 1-(pyrimidin-2-yl)hydrazine-1-carbonitriles was synthesized by base-catalyzed condensation of 3,4-diamino-1,2,4-triazole hydrobromide with several 1,3-dinucleophilic compounds. These final products were formed by ring opening of the 1,2,4-triazolium ring via intermediate 3-amino[1,2,4]triazolo[1,5-a]pyrimidinium bromides.     

Stereoselective reactions of α-silylallyl anions with carbonyl compounds.

α-silylallyl anions of the type 6 react with carbonyl compounds at the γ-position, and stereoselectively to give the E- or Z-isomer depending on the reaction conditions. Solvent and reaction temperature play a critical role in the controle of stereoselectivity.     

From the design of a chiral Lewis acid catalyst to metal-catalyzed coupling reactions

In this perspective, I describe my group's nonobvious path from an interest in chiral Lewis acid catalysis to a project focused on the development of new palladium and nickel catalysts for carbon-carbon bond-forming reactions.