Diastereoselective conjugate addition with acetals,oxazolidines and imidazolidines as chiral auxiliaries

Organocopper reagents undergo highly diastereoselective conjugate addition on cinnamates bearing a chiral oxazolidine or imidazolidine ring.     

Enantiopure beta-hydroxysulfoxide derivatives as novel chiral auxiliaries in asymmetric biaryl Suzuki reactions

[reaction: see text] Highly diastereoselective biaryl Suzuki coupling reactions of (1R)-1-(2-iodo or bromophenyl)-2-(R)-(4-tolylsulfinyl)-1-ethanol derivatives with various aryl- or naphthylboronic acids (or esters) were performed with high yields (up to 99%) and an excellent control of the axial chirality (up to 98% de).     

Planar chiral hydroxy derivatives of [2.2]paracyclophane as auxiliaries for asymmetric allylboration

Allylboronic esters with various structures were synthesized for the first time based on [2.2]paracyclophane derivatives containing one or two hydroxy groups. It was demonstrated that these esters can be used as chiral inductors in the asymmetric allylboration of benzaldehyde. The highest enantiomeric excess of 1-phenylbut-3-en-1-ol (60%) was achieved in the reactions with acyclic bis-O,O′-(paracyclophanyl) allylboronates based on (S)-4-hydroxy-and (S)-12-bromo-4-hydroxy[2.2]paracyclophanes. (S)-4-Hydroxy[2.2]paracyclophane was studied by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2149–2155, November, 2007.     

N-Allyl-N-tert-butyldimethylsilylamine for chiral ligand-controlled asymmetric conjugate addition to tert-butyl alkenoates

The chiral ligand controlled asymmetric conjugate addition reaction of lithium N-allyl-N-(tert-butyldimethylsilyl)amide to alkenoates proceeded smoothly to give, after protodesilylation, the corresponding 3-allylaminoalkanoates with high enantioselectivities in high yields. The allyl group on the nitrogen atom was easily removable to afford 3-aminoalkanoates.     

Asymmetric conjugate addition reaction using pyrazole derivatives as a chiral catalyst

The conjugate addition of Grignard reagent ( 2 ) onto 1‐α,β‐unsaturated)acyl 3,5‐dimethylpyrazole ( 1 ) was enantioselectively catalyzed by the copper complex from cuprous compounds and 3‐phenyl‐l‐mentho‐pyrazole ( 3 ).     

2-Aminopyridine derivatives as potential chiral auxiliaries

2-Bromopyridine and 2-bromo-6-methoxymethylpyridine reacted with an excess of 1-phenylethylamine at reflux giving the aminopyridine derivatives 3a and 3b respectively.     

Ruthenium catalyzed asymmetric dihydroxylation with sultams as chiral auxiliaries

Ruthenium catalyzed asymmetric dihydroxylations of α,β-unsaturated carbonyl compounds with sultams 4, 5 and 6 as chiral auxiliaries are reported.     

A chiral phosphepine–olefin rhodium complex as an efficient catalyst for the asymmetric conjugate addition

A monophosphine–olefin was synthesised from a 2,2′-bridged 1,1′-binaphthyl precursor, which served as a chiral bidentate ligand in the Rh catalysed 1,4-additions of arylboronic acids to cycloalkenones and 5,6-dihydro-2H-pyran-2-one. Fair yields (64–88%) and high asymmetric inductions (88–98% ee) have been obtained. The crystal structure of a corresponding cationic Rh(I) complex was determined.     

New camphor derived chiral ligands for asymmetric synthesis

New enantiomerically pure 1,4-diols and 1,4-aminoalcohols have efficiently been prepared in one and two steps, respectively, from a commercially available camphor derived exo fused lactone. Using sterically hindered amines, an aldol addition of two lactone molecules was observed and the stereochemistry of the products was determined by X-ray crystallography.     

New chiral auxiliaries for highly stereoselective asymmetric methoxyselenenylations

Replacement of the 2-keto group of readily available di(endo-3-camphoryl) diselenide with oxime or O-benzoyloxime substituents, followed by conversion into the corresponding selenenyl triflates, produced highly effective chiral selenium electrophiles for the asymmetric oxyselenenylation of alkenes in the presence of methanol.     

Asymmetric induction in the conjugate addition of thioacetic acid to methacrylamides with chiral auxiliaries

The conjugate addition of thioacetic acid to methacrylamides with chiral C₂-symmetric trans-2,5-disubstituted pyrrolidines afforded the addition products in excellent stereoselectivities (>99% de) and good yields (80–90%). The high selectivity was attributed mainly to the steric effect of the chiral auxiliaries. The cyclic nature of the chiral auxiliaries seemed also important for both the stereoselectivity and the reaction rate. Acidic hydrolysis of the adduct containing (2R,5R)-bis(methoxymethyl)pyrrolidine gave (S)-3-mercapto-2-methylpropanoic acid, a key intermediate for captopril, in 98% ee and 96% yield. The chiral auxiliary was recovered in the demethylated form of N-Boc-(2R,3R)-bis(hydroxymethyl)pyrrolidine in 90% yield.     

Diastereoselective photosensitised radical addition to fumaric acid derivatives bearing oxazolidine chiral auxiliaries

Various fumaric acid diamides were alkylated by reaction with photogenerated radicals. The radicals were produced either by benzophenone triplet hydrogen abstraction (from 1,3-dioxolane, 2-methyl-1,3-dioxolane and adamantane) or via photoinduced electron transfer sensitised by DCN/biphenyl from stannanes (t-BuSnPh₃ and Bu₄Sn). When chiral substrates were employed the reaction occurred with a good degree of stereoselectivity even when acyclic alkyl radicals were involved.     

(S,S)-(+)-Pseudoephedrine as chiral auxiliary in asymmetric conjugate addition and tandem conjugate addition/alpha-alkylation reactions

Organolithium reagents undergo highly regio- and diastereoselective 1,4-addition to (S,S)-(+)-pseudoephedrine enamides furnishing the corresponding beta-alkyl-substituted adducts in excellent yields and diastereoselectivities. In addition, the intermediate lithium enolates generated after the conjugate addition step undergo a highly diastereoselective alkylation reaction, furnishing alpha,beta-dialkyl-substituted amides in high yields. The obtained adducts have been converted into chiral nonracemic beta-alkyl- and alpha,beta-dialkyl-substituted carboxylic acids and gamma-alkyl- and beta,gamma-dialkyl-substituted alcohols using very simple and high-yielding procedures.     

Simple chiral diene ligands provide high enantioselectivities in transition-metal-catalyzed conjugate addition reactions

Chiral dienes possessing the bicyclo[2.2.2]octadiene framework were prepared readily through the [4 + 2] cycloaddition of ( R)-alpha-phellandrene with methyl propiolate as the key step. Diene 9, substituted with a tertiary alcohol on one of the two double bonds, is prepared in just one step from the cycloadduct and is highly effective as a chiral ligand for rhodium-catalyzed asymmetric conjugate addition reactions, giving the corresponding addition products with higher enantioselectivity than other chiral dienes.     

Oxazolidinones as chiral auxiliaries in asymmetric aldol reactions applied to total synthesis

Asymmetric aldol reactions of oxazolidinones as chiral auxiliaries have been achieved and attracted significant consideration as one of the most powerful synthetic tools for the carbon–carbon bond-forming reactions. The methodology has been highly successful in the stereoselective construction of a number of natural products, antibiotics, and other medicinally important compounds. The present review is focused on the utility and versatility of oxazolidinones (Evans chiral auxiliaries) in the asymmetric aldol condensations for the total synthesis of natural products and complex targets.     

New glyco-oxazolidin-2-ones as chiral auxiliaries in boron-mediated asymmetric aldol reactions

Two new chiral glyco-oxazolidin-2-one auxiliaries based on d-glucose are described. Some N-acyl derivatives were synthesized and used in dialkylboron-mediated asymmetric aldol reactions. All reactions delivered as the major diastereomer those predicted by the Zimmerman–Traxler model and were separated by column chromatography and mostly isolated in moderate to good yields.     

Dynamic resolution of α-halo carboxylic acid derivatives in asymmetric nucleophilic substitution using chiral auxiliaries

Recent results on the chiral auxiliary-mediated dynamic resolution of α-halo acid derivatives in nucleophilic substitution have been outlined and classified into two major mechanistic categories, dynamic thermodynamic resolution (DTR) and dynamic kinetic resolution (DKR). Asymmetric nucleophilic substitution of α-halo acid derivatives with various nitrogen, oxygen, sulfur, and carbon nucleophiles is widely used for the stereoselective preparation of α-substituted carboxylic acids.     

Modified guanidines as chiral auxiliaries

Investigations on modified guanidines, prepared by newly developed methods, as potential chiral auxiliaries led to reasonable asymmetric induction not only in catalytic but also in stoichiometric asymmetric syntheses. These guanidine-mediated reactions may contribute to the development of green chemistry because of their possible application as re-cyclable (economically favored) and easily functionalizable (widely applicable) auxiliaries.