Acceleration effect of Lewis acid in allylboration of aldehydes: catalytic,regiospecific, diastereospecific,and enantioselective synthesis of homoallyl alcohols

The addition of pinacol allylboronic esters to aromatic and aliphatic aldehydes smoothly occurred at -78 degrees C in toluene in the presence of a catalytic amount of AlCl3 or Sc(OTf)3 (10 mol %) to give the corresponding homoallyl alcohols in high yields. The reactions proceeded regio- and diastereospecifically, yielding the isomerically pure syn- and anti-homoallyl alcohols from (Z)- and (E)-allylboronic esters, respectively. The protocol was also applied to enantioselective reactions by using a chiral Lewis acid catalyst.     

Characterization of geometrid sex pheromones by electrospray ionization time-of-flight mass spectrometry

The utility of liquid chromatography combined with time-of-flight mass spectrometry (LC/TOFMS) was demonstrated for studies on chiral unsaturated epoxy compounds, sex pheromones produced mainly by female moths in the family Geometridae. By electrospray ionization (ESI), each synthetic epoxyalkadiene derived from (Z,Z,Z)-3,6,9-triene with a C(18)-C(23) straight chain showed three ion series, [M + NH(4)](+), [M + H](+) and [M - OH](+), with high resolution and good sensitivity, indicating its molecular formula. In addition to these, characteristic fragment ions at m/z M - 57 and M - 71 for the 3,4-epoxides and at m/z M - 123 and 123 for the 9,10-epoxides were detected, whereas the 6,7-epoxides did not produce fragment ions that reflected their structures. Monitoring these diagnostic ions during the LC/MS analysis of a gland extract, the natural sex pheromone of the mulberry looper was confirmed to be (Z,Z)-cis-9,10-epoxy-3,6-octadecadiene, which was separable from the other positional isomers on an ODS column. Furthermore, (Z,Z)-cis-3,4-epoxy-6,9-nonadecadiene secreted by the Japanese giant looper was analyzed with a chiral column, and the stereochemistry was determined directly.     

Probing the importance of the hemilabile site of bis(phosphine) monoxide ligands in the copper-catalyzed addition of diethylzinc to N-phosphinoylimines: discovery of new effective chiral ligands

The hemilabile ligand Me-DuPHOS(O) 2 has proven to be a successful ligand for the copper-catalyzed addition of diethylzinc to N-phosphinoylimines. The corresponding alpha-chiral amines were obtained in high yields (80-98%) and enantiomeric ratios (19.0:1 to 99.0:1 er). Furthermore, this Cu* 2 catalytic system has been shown to be effective in the addition of diethylzinc to nitroalkenes and in the reduction of beta,beta-disubstituted vinyl phenyl sulfones. This paper describes a general structure/selectivity study in which the three ligand subunits (chiral phospholane-linker-labile coordinating group (Z)) are systematically modified and tested in the copper-catalyzed addition of diethylzinc to the N-phosphinoylimine 1 derived from benzaldehyde. This study led to the discovery of a new class of effective chiral ligands that combine a chiral phospholane unit and an achiral phosphine oxide.     

Diastereo- and Enantioselective Synthesis of syn-alpha-Vinylchlorohydrins and cis-Vinylepoxides

A new method to generate chiral syn-vinylchlorohydrins and cis-vinyloxiranes is reported. Reaction of (alpha-haloallyl)lithiums with methoxy-9-BBN or Ipc(2)BOMe followed by treatment with BF(3).OEt(2) leads to (Z)-(gamma-haloallyl)boranes which react with aldehydes to yield cis-vinylepoxides (de >/= 90%) upon oxidative workup. Alternatively, addition of ethanolamine to the allylboration product yields syn-alpha-halohydrins (de >/= 90%) that are also easily cyclized to cis-vinylepoxides. Extension of this protocol using [(Z)-gamma-chloroallyl]BIpc(2) leads to chiral syn-alpha-chlorohydrins and cis-vinylepoxides in high de (>/=90%) and ee (90-99%). Enantioselectivity of reactions of chiral (Z)-(gamma-chloroallyl)boranes with aldehydes are more sensitive to reaction conditions than enantioselectivity of reactions of other alpha-or gamma-substituted allylboranes. The effects of proportion of BF(3).OEt(2) and the relative efficacies of LiNR(2) bases on diastereo- and enantioselectivity of the chloroallylation are reported.     

t-BuOK-mediated hydrophosphination of functionalized alkenes: a novel synthesis of chiral P,N- and P,P-ligands

A novel synthesis of effective chiral P,N- and P,P-ligands has been developed by using a t-BuOK-mediated hydrophosphination of chiral alkenylpyridines and alkenylphosphine oxides. Ir complexes of chiral P,N-ligands 1 and 3 gave high enantioselectivities for the hydrogenation of (Z)-alpha-(acetamido)cinnamate 25 and (E)-1,2-diphenylpropene leading to the hydrogenated products with up to 97% ee.     

Diastereoselective conjugate addition to chiral alpha,beta-unsaturated carbonyl systems in aqueous media: an enantioselective entry to alpha- and gamma-hydroxy acids and alpha-amino acids

The stereoselectivity of the ultrasonically induced zinc--copper conjugate addition of iodides to chiral alpha,beta-unsaturated carbonyl systems under aqueous conditions was studied. Alkyl iodides add diastereoselectively to methylenedioxolanone 1 and methyleneoxazolidinone 2 to afford the 1,4-addition products in good yields (38-95 %) and with high diastereomeric excess (44-90 % de). The 1,4-addition to chiral gamma,delta-dioxolanyl-alpha,beta-unsaturated esters 3-5 also proceeds with good yields (51-99 %). The diastereoselectivity is dependent on the geometry of the olefin: the Z isomer 3 gives high diastereoselectivity, while the reactions with the E isomer 4 are nonstereoselective. The reaction proceeds with excellent chemoselectivity and allows the use of iodides bearing ester, hydroxy, and amino groups. Since the 1,4-addition products can be readily hydrolyzed, this methodology constitutes a novel entry for the enantioselective synthesis of alpha- and gamma-hydroxy acids and alpha-amino acids in aqueous media. The results obtained support the radical mechanism proposed by Luche, and represent one of the few examples of a radical stereoselective conjugate addition in aqueous medium.     

Chiral palladium template promoted asymmetric hydrophosphination reaction between diphenylphosphine and vinylphosphines

An organopalladium complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary has been used to promote the asymmetric hydrophosphination reactions between diphenylphosphine and (E)- or (Z)-diphenyl-1-propenylphosphine in high regio- and stereoselectivities under mild conditions. Hydrophosphination of (Z)-diphenyl-1-propenylphosphine with diphenylphosphine gave (S)-(-)-prophos as the major product. Using the same chiral metal template, the corresponding hydrophosphination reaction with (E)-diphenyl-1-propenylphosphine gave (R)-(+)-prophos predominantly. The hydrophosphination reactions generated the asymmetric diphosphines as bidentate chelates on the chiral naphthylamine palladium templates. The template products obtained undergo cis-trans isomerization in solution to form an equilibrium mixture of regioisomers. X-ray analysis of the major template products obtained from the hydrophosphination of (Z)-diphenyl-1-propenylphosphine reveals that the two regioisomers are cocrystallized in a 1:1 ratio. The naphthylamine auxiliary could be removed chemoselectively from the template products by treatment with concentrated hydrochloric acid to form the corresponding optically pure neutral complexes [(R)- or (S)-(prophos)PdCl(2)]. Subsequently, the (R)- and (S)-dichloro complexes undergo ligand displacement with aqueous cyanide to generate the corresponding optically pure diphosphine ligands in high yields. Mechanistic pathways explaining the stereoselectivity of the chiral organopalladium template promoted hydrophosphination reactions are also proposed.     

Pressure control of enantiodifferentiating photoisomerization of cyclooctenes sensitized by chiral benzenepolycarboxylates. The origin of discontinuous pressure dependence of the optical yield

Pressure effects on enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-cycloocta-1,5-diene sensitized by chiral benzene-1,2,4,5-tetracarboxylate were investigated over a pressure range of 0.1-750 MPa. Enantiomeric excesses (ee's) of the (E)- and (E.Z)-isomers obtained displayed discontinuous pressure dependencies, affording distinctly different differential activation volumes (delta delta V++) for each range, indicating alteration of the enantiodifferentiation mechanism. The switching of delta delta V++ occurred at essentially the same pressures of 200 and 400 MPa, which are shared by all the chiral sensitizers, irrespective of the chiral auxiliary employed. Circular dichroism spectral examinations at pressures of up to 400 MPa also revealed that the chiral sensitizers undergo discontinuous conformational changes at 200 MPa, which most likely lead to switching of the enantiodifferentiating sensitization mechanism in the exciplex intermediate.     

Direct, stereospecific generation of (Z)-disubstituted allylic alcohols

A one-pot method to prepare highly functionalized (Z)-disubstituted allylic alcohols is introduced. Hydroboration of a variety of 1-bromo-1-acetylenes with dicyclohexyl borane, reaction with t-BuLi, and transmetalation to zinc generates a (Z)-disubstituted vinylzinc reagent. In situ reaction of this reagent with aldehydes generates (Z)-disubstituted allylic alcohols in high yields (81-97%). Addition to chiral protected alpha- or beta-oxygenated aldehydes proceeds with diastereoselectivities between 6:1 and 18:1. The anti-Felkin product is obtained in most cases.     

Tandem transesterification and intramolecular cycloaddition of alpha-methoxycarbonylnitrones with chiral acyclic allyl alcohols: systematic studies on the factors affecting diastereofacial selectivity of the cycloaddition

Factors affecting the stereochemical course of the intramolecular cycloaddition of intermediary alpha-allyloxycarbonylnitrone resulting from transesterification of alpha-methoxycarbonylnitrones 1a-d with chiral allyl alcohols 5 or 6 were investigated systematically. It was found that the factors of diastereofacial selection are highly dependent on the geometries of the allyl alcohols. In the cases where primary or secondary chiral (Z)-allyl alcohols are used, A(1,3)-strain arising from the chiralities in the (Z)-nitrone transition states of the intramolecular cycloaddtion is the most important factor. In contrast, in the case of the reaction using chiral nitrones 1c,d and (E)-allyl alcohols, steric interaction between the chiral N-substituent and the trans substituent of the olefin moiety in the intermediate is dominant. These aspects were applied to geometry-differentiated cycloaddition using a mixture of (E)-5 and (Z)-5. As a typical example, treatment of bulky 1b with a 1:1 mixture of (E)-5 and (Z)-5 in the presence of a catalytic amount of TiCl(4) and MS 4A gave 7b as the predominant product among four possible products.     

Enantiodifferentiating photoisomerization of (Z,Z)-1,3-cyclooctadiene included and sensitized by naphthoyl-curdlan

6-O-(2-naphthoyl)curdlan was newly synthesized as a sensitizing polysaccharide host to examine the chiroptical properties, supramolecular complexation, and photochirogenic behavior with (Z,Z)-1,3-cyclooctadiene (1ZZ). The enantiodifferentiating photoisomerization of 1ZZ included and sensitized by this polysaccharide host gave a highly strained chiral (E,Z)-isomer in up to 8.7% enantiomeric excess (ee) in solution and 11.7% ee in the solid state, which are the highest values ever reported for a supramolecular photochirogenesis of 1EZ.     

Stereoselective formation of N-acyliminium ion via chiral N,O-acetal TMS ether and its application to the synthesis of beta-amino acids

[reaction: see text] The highly stereoselective synthesis of beta-amino acids via the chiral 4-phenyloxazolidinone-controlled linear N-acyliminium ion reaction has been achieved by employing chiral N,O-acetal TMS ethers. In addition, the mechanism of the excellent stereochemical outcome has been elucidated. The oxazolidinone auxiliary plays a dual role in stereocontrol: the E/Z geometry control of the N-acyliminium ion induced by an initial stereoselective amide reduction, leading to the chiral N,O-acetal TMS ether, and face control of the nucleophile attack in the N-acyliminium ion reaction.     

天然和修饰环糊精的不对称光化学

用修饰的α-,β-,γ-环糊精(CDs)的包结增感作用研究(Z)-环辛烯(1Z)向手性(E)-异构体(1E)的超分子对映差向光异构反应。建立定量圆二色(CD)和差圆二色(DCD)公式, 研究修饰α-,β-,γ-环糊精衍生物与1Z包结反应的构象、化学量和稳定常数。 实验发现结合诱导的CD光谱变化是温度和修饰环糊精浓度的临界函数。同时发现光稳态E/Z随照射时间增长而增加最后达到光稳定状态, 但明显依赖于增感剂结构和溶液中甲醇含量,它与环糊精手性空腔被客体1Z占有率有直接关系。考查含o-,m-,p-羧酸甲酯基团的苯甲酸β-环糊精酯衍生物的光增感和对映差向能力,更好地认识到在CDs空腔内的有效光能转换是怎样发生的。用邻苯二甲酸β-环糊精酯的对映体过剩（ee）从2.9% 增加到24%。有趣的是产物的ee值与取代基常数（Hammett,σ）间没有明显的关系,却与某些苯甲酸β-CD酯的主体占有率有直接关系,即是通过分析在不同甲醇含量的水溶液中被一些β-CD衍生物增感的对映差向光异构反应中的ee,得出被底物1Z占有主体空腔的百分率 。     

Stereochemically controlled asymmetric 1,2-reduction of enones mediated by a chiral sulfoxide moiety and a lanthanum(III) ion

Enantiomerically pure (Z)-β-sulfinyl allylic alcohols of either handedness can be readily prepared from (Z)-β-sulfinyl enones using NaBH(4) or DIBAL reductants in the presence of LaCl(3) as a chelating agent. A chiral sulfoxide auxiliary induces the remote 1,2-asymmetric reduction (1,4-induction) to afford various chiral allylic alcohols in high yields with excellent stereoselectivities (up to 100% de).     

Copper-catalyzed anti-hydrophosphination reaction of 1-alkynylphosphines with diphenylphosphine providing (Z)-1,2-diphosphino-1-alkenes

Hydrophosphination of 1-alkynylphosphines with diphenylphosphine proceeds in an anti fashion under copper catalysis, providing an easy and efficient access to a variety of (Z)-1,2-diphosphino-1-alkenes and their sulfides. The reaction is highly chemoselective and can be performed even in an aqueous medium. The reaction is reliable enough to realize a gram-scale synthesis of (Z)-1,2-diphosphino-1-alkene. Radical reduction of the diphosphine disulfides with tris(trimethylsilyl)silane yields the parent trivalent diphosphines without suffering from the isomerization of the olefinic geometry. Enantioselective hydrogenation of (Z)-3,3-dimethyl-1,2-bis(diphenylthiophosphinyl)-1-butene followed by desulfidation leads to a new chiral bidentate phosphine ligand.     

Synthesis and properties of chiral stilbene diacrylates

Two chiral and isomerizable liquid crystalline diacrylates were synthesized. The purpose of these compounds was to tune the helical twisting power of cholesteric materials containing these compounds by means of an E - Z photoisomerization of the photoactive group derived from stilbene. The photochemical behaviour of these compounds was studied with the aid of two model compounds containing the same isomerizable mesogenic group. The mesogenic group derived from 4-(4-hydroxybenzoyloxy)-4'-hydroxystilbene decomposes upon irradiation. Its isomer, derived from 4-(4-hydroxyphenoxycarbonyl)-4'-hydroxystilbene, shows a clean E - Z isomerization. The HTP of the chiral diacrylate derived from the latter mesogenic group changes from 7 to 3 µm -1 in dilute nematic solution. Colour changes in a cholesteric material containing this compound were observed. The effect was very dependent on temperature and concentration due to the strong smectic character of this diacrylate.     

Asymmetric three- and [2 + 1]-component conjugate addition reactions for the stereoselective synthesis of polysubstituted piperidinones

The efficiency and stereoselectivity of the conjugate addition of lithium (Z)- or (E)-beta-amino ester enolates, generated by lithium amide conjugate addition to an alpha,beta-unsaturated ester or deprotonation of a beta-amino ester, respectively, to a range of alpha,beta-unsaturated acceptors has been investigated. Deprotonation of a beta-amino ester with LDA, followed by conjugate addition to a chiral alpha,beta-unsaturated oxazolidinone gives high 2,3-anti selectivity ( approximately 90% d.e.), with hydrogenolysis and purification to homogeneity generating stereodefined trisubstituted piperidinones as single stereoisomers. Asymmetric three-component couplings of alpha,beta-unsaturated esters and alkylidene malonates initiated by lithium amide conjugate addition proceeds with high levels of 2,3-anti stereoselectivity, with hydrogenolysis giving tetrasubstituted piperidinones.     

Enantioselective Michael reactions of chiral secondary enaminoesters with 2-substituted nitroethylenes. Syntheses of trans, trans-2,4-disubstituted pyrrolidine-3-carboxylates

The Michael reaction of chiral 3-substituted secondary enaminoesters with 2-substituted nitroethylenes leads to (Z)-adducts, with good to excellent diastereoselectivity. The nitro group of these adducts was catalytically reduced to give, after cyclization and chiral amine elimination, pyrrolines or pyrrolidines after further reduction. In particular, the syntheses of ethyl (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate are described.     

Enantiodifferentiating photoisomerization of cyclooctene included and sensitized by aroyl-beta-cyclodextrins: a critical enantioselectivity control by substituents

A series of 6-O-benzoyl-beta-cyclodextrins (CDs) with methyl, methoxy, methoxycarbonyl, and bromo substituent(s) at the ortho-, meta-, and/or para-position(s) were synthesized as chiral sensitizing hosts for the use in supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to its chiral (E)-isomer (1E). The complex stability constants (K(S)) of the modified beta-CDs with 1Z in aqueous methanol solutions were highly sensitive to the substituent(s) introduced to the benzoate moiety, and the log K(S) values decreased linearly with slightly different slopes with increasing methanol content. The enantiomeric excess (ee) of 1E obtained upon photosensitization with these hosts was a critical function of the size and position of the substituent, varying from almost zero to 46% ee. This indicates that even an apparently small structural difference between methyl and methoxy can critically affect the enantiodifferentiating photoisomerization of a guest included in the chiral cavity, probably through manipulation of both the orientation of ground-state 1Z and the subsequent rotational relaxation of excited 1Z inside the chiral cavity.     

5-L-孟氧基4-苄氨基丁烯内酯的不对称合成和晶体结构研究

温和条件下,苄胺与手性合成子5-(L)-孟氧基3-溴-2(5)呋喃酮通过串联的不对称迈克尔加成/分子内消除反应合成了一种新手性化合物:5-L-孟氧基-4-苄胺基丁烯内酯。产物经过IR、1H-NMR、MS谱学表征,并经X-ray单晶衍射测定了其结构。新化合物属于正交晶系,P212121空间群,a=5.2945(4),b=14.2829(10),c=26.0769(18),Mr=343.45,Z=4,V=1972.0(2)3,Dc=1.157g/cm3,μ(MoKα)=0.076mm-1,F(000)=744,R=0.0387,wR=0.0880。