Rh(I)-catalyzed enantioselective hydrogenation of (E)- and (Z)-beta-(acylamino)acrylates using 1,4-bisphosphine ligands under mild conditions

[reaction: see text] Rh-Me-BDPMI (1a) complex can be an effective catalyst for the hydrogenations of (E)- and (Z)-beta-(acylamino)acrylates, in which the Z-isomers hydrogenated with the same or even higher ee values than the corresponding E-isomers. The conversion yield and enantioselectivity of E- and Z-isomers were largely dependent on the solvent, and thus, the E-isomers were hydrogenated more effectively in CH(2)Cl(2), whereas the Z-isomers were hydrogenated more effectively in polar MeOH solvent.     

Ru-catalyzed highly enantioselective hydrogenation of beta-alkyl-substituted beta-(acylamino)acrylates

Highly enantioselective hydrogenation of beta-alkyl-substituted (E)-beta-(acylamino)-acrylates catalyzed by Ru((R)-Xyl-P-Phos)(C(6)H(6))Cl(2) complex (cat. 1c) was achieved in up to 99.7% ee. Moderate to good enantioselectivities in the hydrogenation of corresponding (Z)-isomers in the presence of [Rh((R)-Xyl-P-Phos)(COD)]BF(4) (cat. 2c) were also obtained. The results demonstrated that the electronic and steric properties of the dipyridylphosphine ligands as well as the different transition metal ions have significant influences on the catalytic properties in the hydrogenation of beta-(acylamino)acrylates.     

Synthesis of β-amino acid derivatives via copper-catalyzed asymmetric 1,4-reduction of β-(acylamino)acrylates

A new set of reaction conditions has been established to facilitate the copper-catalyzed enantioselective 1,4-reduction of β-(acylamino)acrylates toward a selection of β-alkyl-β-amino acid derivatives in high yields and with uniformly high ee values (up to 99%) irrespective of the use of (E)- or (Z)-substrates.     

Highly enantioselective hydrogenation of (E)-beta-(acylamino)acrylates catalyzed by Rh(i)-complexes of electron-rich P-chirogenic diphosphines

Excellent enantioselectivities up to 99.7% were achieved in the hydrogenation of (E)-beta-(acylamino)acrylates by the use of Rh(I)-complexes of electron-rich diphosphines, t-Bu-BisP and t-Bu-MiniPHOS. Low-temperature NMR experiments testify that monohydrides with beta-carbon atom of the substrate bound to rhodium are involved in the catalytic cycle.     

Highly effective chiral ortho-substituted BINAPO ligands (o-BINAPO): applications in Ru-catalyzed asymmetric hydrogenations of beta-aryl-substituted beta-(acylamino)acrylates and beta-keto esters

A novel family of chiral ortho-substituted BINAPO ligands (o-BINAPO) were synthesized from BINOL, and their Ru complexes were highly efficient catalysts for asymmetric hydrogenation of beta-aryl-substituted beta-(acylamino)acrylates and beta-aryl-substituted beta-keto esters. The Ru-bisphosphinite catalysts can tolerate an E/Z mixture of beta-aryl-substituted beta-(acylamino)acrylates. These highly enantioselective hydrogenations provide a useful way to prepare beta-aryl-substituted beta-amino acids and beta-hydroxyl acids.     

BoPhoz类膦-氨基膦配体在Rh-催化β-脱氢氨基酸酯的不对称氢化反应中的应用

将BoPhoz类膦-氨基膦配体应用在Rh-催化β-脱氢氨基酸酯的不对称氢化反应中,考察了配体结构及反应条件对反应结果的影响,并在优化的条件下研究了各种底物的适用范围,产物的对映选择性达81％ee．     

Highly efficient synthesis of chiral beta-amino acid derivatives via asymmetric hydrogenation

The Rh-TangPhos complex is an efficient hydrogenation catalyst for making chiral beta-amino acid derivatives. With the Rh-TangPhos system, high enantioselectivities (up to 99.6%) and turnover numbers have been obtained in the hydrogenation of E/Z isomeric mixtures of both beta-alkyl and beta-aryl beta-(acylamino)acrylates. [reaction: see text]     

A novel class of P-O monophosphite ligands derived from D-mannitol: broad applications in highly enantioselective Rh-catalyzed hydrogenations

We report on a new class of P-O monophosphite ligands (designated 3a-k) with a double six-membered-ring backbone onto which are attached additional groups and on applications of their Rh complexes in the hydrogenation of enamides, alpha-dehydroamino acid esters, dimethyl itaconate, and beta-(acylamino)acrylates. Our results demonstrate that the Rh complexes with ligands 3a-k exhibit high enantioselectivity and reactivity in asymmetric hydrogenation reactions. An ee value of up to 98.0% was obtained for the hydrogenation of alpha-dehydroamino acid esters, and the ee values were all over 99% for the other three types of substrate, with a turnover number of up to 5000.     

Base-mediated stereospecific synthesis of aryloxy and amino substituted ethyl acrylates

The stereospecific synthesis of aryloxy and amino substituted E- and Z-ethyl-3-acrylates is of interest because of their potential in the polymer industry and in medicinal chemistry. During work on a copper-catalyzed cross-coupling reaction of ethyl (E)- and (Z)-3-iodoacrylates with phenols and N-heterocycles, we discovered a very simple (nonmetallic) method for the stereospecific synthesis of aryloxy and amino substituted acrylates. To study this long-standing problem on the stereoselectivity of aryloxy and amino substituted acrylates, a series of O- and N-substituted nucleophiles was allowed to react with ethyl (E)- and (Z)-3-iodoacrylates. Screening of different bases indicated that DABCO (1,4-diazabicyclo[2.2.2]octane) afforded successful conversion of ethyl (E)- and (Z)-3-iodoacrylates into aryloxy and amino substituted ethyl acrylates in a stereospecific manner. Herein are the details of this DABCO-mediated stereospecific synthesis of aryloxy and amino substituted E- or Z-acrylates.     

金鸡钠碱催化烯胺的不对称C-亚磺酰化反应

以金鸡钠碱催化烯胺的不对称C-亚磺酰化反应,产物(E,Z)-N-苄氧羰基-2-苯亚磺酰基-1-苯基丙烯胺[(E,Z)-4],收率71%,立体选择性E:Z=3:2,其中(E)-4和(Z)-4的对映选择性分别为75%ee和93%ee。     

Readily available chiral phosphine–aminophosphine ligands derived from 1-phenylethylamine for Rh-catalyzed enantioselective hydrogenations

A series of new chiral phosphine–aminophosphine ligands have been prepared via a two- or three-step transformation from commercially available and inexpensive (S)-1-phenylethylamine, and successfully used in the rhodium-catalyzed asymmetric hydrogenation of various enamides, β-dehydroamino acid esters, and dimethyl itaconate. The results show that the ligand structure plays an important influence on both the reactivity and enantioselectivity. Ligand 2d bearing a N–H proton and two F-atoms on the 3,5-positions of the phenyl ring of the aminophosphino moiety was most effective for the hydrogenation of enamides and (Z)-β-aryl-β-(acylamino)acrylates, whereas ligand 1b showed the highest enantioselectivities in the hydrogenation of (Z)-β-alkyl-β-(acylamino)acrylates and dimethyl itaconate.     

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 construction of a beta-isopropenyl alcohol moiety at the C(2) and (3) of kallolide A and pinnatin a using a [2,3] Wittig rearrangement of cyclic furfuryl ethers

A stereocontrolled synthesis of anti- and syn-beta-isopropenyl alcohol moieties at the C(2)-C(3) positions of kallolide A and pinnatin A was accomplished employing the [2,3] Wittig rearrangement of (E)-and (Z)-cyclic furfuryl ethers 8. Enantioselective Wittig rearrangement of (E)- and (Z)-furfuryl ethers 8 using butyllithium and a chiral bis(oxazoline) was also examined to provide (2R,3R)-homoallylic alcohol anti-9 in up to 61% ee and (2R,3S)-syn-9 in up to 93% ee, respectively.     

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 。     

三乙烯二胺催化Michael加成对(E)-β-芳(烷)氧基丙烯酸酯的立体选择性合成

以异丙醇为溶剂(或无溶剂),采用三乙烯二胺(DABCO)催化的取代苯酚(或取代苄醇)与2-丁炔酸乙酯的Michael加成反应合成了14个(E)-β-芳氧基丙烯酸酯化合物(3a~3n,3f~3n为新化合物)和3个烷氧基丙烯酸酯化合物(5a,5b和5k,5b和5k为新化合物),收率分别为85%~99%和60%~68%,其结构经1H NMR,13C NMR和HR-MS(ESI)表征。以3a的合成为例,优化了合成3的反应条件。结果表明:在最优反应条件(DABCO为催化剂,异丙醇为溶剂,于25℃反应9 h)下,3a收率92%,E∶Z99∶1。     

Enantioselective hydrogenation of tetrasubstituted olefins of cyclic beta-(acylamino)acrylates

Hydrogenation of a series of cyclic beta-(acylamino)acrylates with tetrasubstituted olefins has been accomplished successfully with the use of Ru catalysts with chiral biaryl ligands such as C3-TunaPhos, and up to over 99% ee's have been achieved. This methodology provides an efficient catalytic method for the synthesis of both cis and trans chiral cyclic beta-amino acid derivatives.     

Highly enantioselective reduction of beta,beta-disubstituted aromatic nitroalkenes catalyzed by Clostridium sporogenes

This is the first report of the use of Clostridium sporogenes extracts for enantioselective reduction of CC double bonds of beta,beta-disubstituted (1) and alpha,beta-disubstituted nitroalkenes (3). Crude enzyme preparations reduced aryl derivatives 1a-e and 1h, in 35-86% yield with > or =97% ee. Reduction of (E)- and (Z)-isomers of 1c gave the same enantiomer of 2c (> or =99% ee). In contrast, alpha,beta-disubstituted nitroalkene 3a was a poor substrate, yielding (S)- 4a in low yield (10-20%), and the ee (30-70% ee) depended on NADH concentration. An efficient synthesis of a library of nitroalkenes 1 is described.     

Asymmetric conjugate reductions with samarium diiodide: asymmetric synthesis of (2S,3R)- and (2S,3S)-[2-2H,3-2H]-leucine-(S)-phenylalanine dipeptides and (2S,3R)-[2-(2)H,3-2H]-phenylalanine methyl ester

The highly diastereoselective samarium diiodide and D(2)O-promoted conjugate reduction of homochiral (E)- and (Z)-benzylidene and isobutylidene diketopiperazines (E)-5,7 and (Z)-6,8 has been demonstrated. This methodology allows the asymmetric synthesis of methyl (2S,3R)-dideuteriophenylalanine 27 in > or = 95% de and >98% ee, and (2S,3R)- or (2S,3S)-dideuterioleucine-(S)-phenylalanine dipeptides 37 and 38 in moderate de, 66% and 74% respectively. A mechanism is proposed to account for this process.     

Gold(I)-catalyzed intramolecular amination of allylic alcohols with alkylamines

A 1:1 mixture of (1)AuCl [1 = P(t-Bu)(2)o-biphenyl] and AgSbF(6) catalyzes the intramolecular amination of allylic alcohols with alkylamines to form substituted pyrrolidine and piperidine derivatives. Gold(I)-catalyzed cyclization of (R,Z)-8-(N-benzylamino)-3-octen-2-ol (96% ee, 95% de) led to isolation of (R,E)-1-benzyl-2-(1-propenyl)piperidine in 99% yield with 96% ee, consistent with the net syn addition of the amine relative to the departing hydroxyl group.     

Enantio- and diastereoselective synthesis of (E)-1,5-syn-diols: application to the synthesis of the C(23)-C(40) fragment of tetrafibricin

A highly stereoselective synthesis of (E)-1,5-syn-diols 6 is described. The kinetically controlled hydroboration of allenyltrifluoroborate 8 with Soderquist borane 2 provides the (Z)-allylic trifluoroborate 9, which undergoes sequential allylboration with two different aldehydes to provide (E)-1,5-syn-diols 6 in 72-98% yields with >95% ee and >20:1 dr. Application of this method to the synthesis of the tetrafibricin C(23)-C(40) fragment 19 is described.