Stereoselective synthesis of chiral 3-aryl-1-alkynes from bromoallenes and heterocuprates

The synthesis of chiral 3-aryl-1-alkynes 3 via cross-coupling of 3-alkyl- and 3,3-dialkyl-1-bromo-1,2-dienes 1 and arylbromocuprates (RCuBr)MgBr.LiBr 2 was examined. With phenylcopper reagents and its para-substituted derivatives, as well as with 2-naphthyl cuprates, the reaction gave compounds 3 with high regioselectivity and good yields on the chemically pure product. On the contrary, when ortho-substituted phenyl reagents and 1-naphthyl cuprates were used, the regioselectivity of the process was very dependent upon the steric requirements of the alkyl substituents on the bromoallenic substrate. When the steric bulk was increased, remarkable quantities of isomeric arylallenes 4 were also observed in the reaction mixtures. The high 1,3-anti stereoselectivity of the coupling process allowed us to obtain enantiomerically enriched 3-aryl-1-alkynes from optically active allenic substrates, thus indicating a simple pathway toward the synthesis of quaternary stereogenic centers characterized by an aryl group. A possible cross-coupling mechanism was also suggested to explain the regio- and stereochemical data. For the preparation of omega-functionalized 3-phenyl-1-alkynes, the reaction of 1-bromo-3-phenylpropadiene with Knochel reagents RCu(CN)ZnCl.2LiCl was also studied; this reaction led to the acetylenic compounds in high yields mainly when the R group (also omega-functionalized) on the copper reagent was primary.     

Organocatalytic asymmetric aza-Michael addition of pyrazole to chalcone

An efficient enantioselective aza-Michael addition of pyrazole to chalcone was established. In the presence of the primary amine derived from cinchona alkaloid and acidic additive, the reactions afforded 1,4-adducts in high yields (up to 98%) with 68–88% ee.     

Asymmetric Michael addition of 2-nitropropane to a chalcone catalyzed by chiral crown ethers incorporating a D-glucose unit

Michael addition of 2-nitropropane 4 to a chalcone 3 catalyzed by crown ethers incorporating two glucose units (of 1 type) afforded the adduct 5 with an R-enantiomer excess (28% ee) while the aza-crown ethers containing one glucose unit (of 2 type) gave the same adduct favoring the S-enantiomer under solid–liquid phase transfer conditions (SL-PT). It was proven that substituents at the N-atom of the crown ring in 2 have a significant effect on both the chemical yield and the enantioselectivity, and those having heteroatoms in the proper position of the side chain ( 2e , 2f ) showed the best results in this reaction: 65% ee for the S-antipode. The absolute configuration of (+)-4-methyl-4-nitro-1,3-diphenyl-1-pentanone ( 5 ), determined by X-ray diffraction, is also presented in this article. © 1997 John Wiley & Sons, Inc.     

Reagent controlled addition of chiral sulfur ylides to chiral aldehydes

The degree of reagent and substrate control in the reaction of chiral sulfur ylides with chiral aldehydes has been investigated. Specifically, the reactions of the two enantiomers of the chiral benzyl sulfonium salt 1 with glyceraldehyde acetonide were studied in detail. Of the two new stereogenic centers created, it was found that the C1 stereochemistry was largely controlled by the reagent, whereas control at the C2 center was dependent on the aldehyde used. In one case, the trans isomer was produced via reversible formation of the intermediate betaine, whereas in the alternative case, the C2 center was under Felkin Anh/Cornforth control through non-reversible formation of the betaine. Thus, the aldehyde stereocenter influenced the degree of reversibility in betaine formation, which impacted on the stereocontrol at the C2 position.     

Synthesis of chalcone analogs -4- and 5-nitropyrrole derivatives

Nitropyrrole analogs of chalcone have been synthesized by aldol condensation in basic medium from 5-nitropyrrole-2-carboxaldehyde, 4- and 5-nitro-2-acetylpyrrole, and the corresponding aromatic aldehydes and methyl ketones; their 2, 4-dinitrophenylhydrazones have been obtained. Some considerations are expressed concerning the reactivity of pyrrole-2-carboxaldehyde, 2-acetylpyrrole, and their nitro derivatives.     

Synthesis of novel norephedrine-based chiral ligands with multiple stereogenic centers and their application in enantioselective addition of diethylzinc to aldehyde and chalcone

Novel norephedrine-based chiral ligands with multiple stereogenic centers were conveniently prepared from norephedrine and N-substituted pyrrole. These novel chiral ligands were used to catalyze the enantioselective addition of diethylzinc to aldehydes and to chalcone in high yields and with good to high enantioselectivities. The absolute configuration of products was found to be affected by the stereogenic centers on the norephedrine part of the novel chiral ligands.     

Radical addition reaction of alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one

Quantum chemical calculations of the parameters of the 1-(4-nitrophenyl)-5H-pyrrolin-2-one molecule have been carried out by the MNDO method. The radical addition reaction of aliphatic, alicyclic, and aromatic alcohols to 1-(4-nitrophenyl)-5H-pyrrolin-2-one with the formation of 3- and 4-substituted pyrrolidones has been investigated.Kuban State Technological University, Krasnodar 350072, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 934–938, July, 1998.     

Highly stereoselective addition of silylphosphines to chiral aldehydes

The reaction between diphenyl(trimethylsilyl)phosphine and chiral aldehydes proceeds with high stereoselectivity to give diastereomerically pure tertiary α-trimethylsiloxyalkylphosphines. The diastereomeric purity of the addition products was 90-100%. The products were purified via the formation of borane-phosphine complexes. The reaction of bis(trimethylsilyl)phenylphosphine with acetonide (R)-glyceraldehyde provides tertiary bis(glyceryl)phosphines.     

Diastereoselective addition of organomanganese compounds to chiral polyalkoxyaldehydes

Organomanganese compounds RMnI (R=Me, Pr, Bu, Hex, Ph, BuCC) prepared from RLi and MnI₂ in Et₂O react with 3-O-benzyl-1,2-O-isopropylidene--D-xylo-pentodialdo-1, 4-furanose, 1,23,4-di-O-isopropylidene--D-galacto-hexodialdo-1,5-pyranose, andR-2,3-dibenzyloxypropanal to afford 4,5-threo-, 5,6-threo-, and 2,3-threo-isomeric products, respectively, with high diastereoselectivity.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1122–1126, June, 1993.     

Aza-Michael addition of chiral hydrazines to alkylidene malonates

The conjugate spontaneous addition of chiral N,N-dialkylhydrazines 1 to dimethyl alkylidene/arylidene malonates 2, 5-10 affords the corresponding β-hydrazino esters in moderate-to-good yields and selectivities. d-Mannitol-derived hydrazine 1a afforded best results, mainly due to the higher stability of the products 3, 11-16.     

Steric consequence of the diastereoselective addition of chiral lithium 2-(1-dimethylaminoethyl)phenyl cuprates to some enones

Conjugate addition of the mixed chiral species lithium [(S)-2-(1-dimethylaminoethyl)phenyl](2-thienyl)cuprate to (E)-4-phenyl-3-buten-2-one, 2-cyclohexenone or to 2-cyclopentenone proceeds with high diastereoselectivity. The first two enones gave crystalline adducts directly, while the non-crystalline cyclopentenone adduct was converted into a crystalline methiodide. The crystal structures of the compounds have been determined from single-crystal X-ray diffractometer data in order to reveal the configurations at the new chiral centres. In all three cases the configuration at the new asymmetric centre is S. (S,S)-4-[2-(1-Dimethylaminoethyl)phenyl]-4-phenyl-2-butenone, C₂₀H₂₅NO, crystallizes in space group P2₁ with a 7.604(2), b 9.398(5), c 12.290(6) Å, β 92.30(3)° and Z = 2. Full-matrix least-squares refinement of 273 structural parameters gave R = 0.066 for 1015 observed independent reflections. (S,S)-3-[2-(1-Dimethylaminoethyl)phenyl]-2-cyclohexanone, C₁₆H₂₃NO crystallizes in space group P2₁2₁2₁ with a 12.499(4), b 6.645(3), c 17.568(7) Å and Z = 4. Full-matrix least-squares refinement of 142 structural parameters gave R = 0.068 for 1507 observed independent reflections. (S,S)-1-[2-(3-Oxocyclopentyl)phenyl]ethyltrimethylammonium iodide, C₁₆H₂₄NOI, crystallizes in space group P4₁, with a 10.569(3), c 30.895(7) Å and Z = 8; there are thus two crystallographically independent cations in the asymmetric unit. Full-matrix least-squares refinement of 342 structural parameters gave R = 0.054 for 2119 observed independent reflections.The (S,S)-configuration observed in these adducts indicates that the conjugate addition gives the least crowded lithium enolate as the major product.     

Nonlinear effects in the enantioselective 1,4-conjugate addition of diethylzinc to chalcone

A clear positive nonlinear effect of the enantiopurity of ligand 1 on the product ee was observed in the enantioselective 1,4-conjugate addition of Et₂Zn to chalcone. The experimental data of nonlinear effect meet Kagan's ML₂ model.     

Diastereoselective addition of chiral azomethine ylides to cinnamoyl moieties,attached to chiral auxiliaries

Doubly diastereoselective 1,3-dipolar cycloadditions of chiral azomethine ylides to cinnamoyl moieties, attached to chiral auxiliaries, were investigated. The resulting trans-3,4-disubstituted pyrrolidines were obtained in diastereomeric ratios of up to 78:22. The influence on this ratio by the constitution of the chiral ylide was found to be rather small.     

Stereoselective double addition of chiral alkynyl-zincs to cobalt-stabilized acetylenedicarbaldehyde

Acetylenedicarbaldehyde, a desirable but intractable C₄ synthon, can be protected as the Gorgues’ dicobalt hexacarbonyl complex. It undergoes chimio-, diastereo- and enantioselective attack of terminal alkynes using zinc triflate and (−)-N-methyl-ephedrine to afford stable complexes of chiral secondary carbinol-skipped oligoynes.     

Efficient stereoselective nucleophilic addition of pyrroles to chiral nitrones

Regioselective additions of pyrroles to a variety of optically active nitrones under smooth acidic conditions lead to chiral pyrrolic N-hydroxylamines in good to excellent yields. Depending on the position of the chirality on the nitrone partner, the addition products have been isolated with high diastereoselectivity levels. Reaction of glyoxylate based chiral nitrones either at the C-2 or at the C-3 position of the pyrrole nucleus afforded N-hydroxyamino esters in high yields as single diastereoisomers. These adducts allow access to enantio-enriched non proteinogenic 2'- and 3'-pyrrolylglycines (13 and 19 respectively).     

The steric course of iodine halogenide addition to 1-methy1-4-t-butylcyclohexene: Influence of iodinating species

The addition of IC1 and IBr to 1-methyl-4-t-butylcyclohexene has been investigated in chloroform and carbon tetrachloride and the distribution of the produced trans-iodohalogenides has been determined by NMR spectroscopy. The stereoselectivity of the addition was found to be determined by both the reversible electrophilic first step and the nucleophilic second step. The higher stereoselectivity of the addition of IBr is interpreted on the basis of the higher softness of bromide ion with respect to chloride ion.     

Enantioselective synthesis of alpha-substituted ketones by asymmetric addition of chiral zinc enamides to 1-alkenes

A zinc enamide of a chiral imine derived from a ketone and (S)-valinol or (S)-t-leucinol undergoes addition to 1-alkene to generate a gamma-zincioimine intermediate, which reacts with a carbon electrophile to give upon hydrolysis an optically active alpha-substituted ketone in good yield. The stereoselectivity of the addition reaction may reach 99% for the reaction of a cyclohexanone imine with ethylene.     

2-amino-substituted 1-sulfinylferrocenes as chiral ligands in the addition of diethylzinc to aromatic aldehydes

A simple and modulable access to a structural variety of enantiopure amino-substituted ferrocenyl sulfoxides and their use as chiral catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes is described. Moderate to high enantioselectivities (up to 96% ee) were obtained in the case of the arylsulfonamide ligands (R(Fc), R(S))-4h and (R(Fc), R(S))-4i. It has been demonstrated that the planar chirality of the ferrocene unit is the decisive chiral element involved in the reaction.     

Structurally constrained C1-1,1′-bisisoquinoline-based chiral ligands: geometrical implications on enantioinduction in the addition of diethylzinc to aldehydes

New highly constrained chiral C₁-1,1′-bisisoquinoline ligands have been synthesized. X-ray crystallographic analysis of these ligands showed peculiar structural differences between the parent 1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline and its alkyl, acyl and sulfonyl derivatives. The consequences of their geometrical conformations on enantioinduction were examined by employing the enantioselective addition of diethylzinc to aldehydes. Such conformations greatly affected the catalytic efficiency of these ligands.     

Conjugate addition of amines to chiral 3-aziridin-2-yl-acrylates

Conjugate addition of benzylamine to chiral methyl cis-3-aziridin-2-yl-acrylates was successfully proceeded to yield 3-aziridin-2-yl-3-benzylaminopropionates in high yield with high stereoselectivity. The addition products were used for the asymmetric synthesis of vicinal diamine derivatives including 4-amino-5-methylpyrrolidin-2-one, 3,4-diaminopentanoate, and 5-chloromethyl-4-alkoxycarbonylmethylimidazolidin-2-one.