3-Alkoxymethyl-1-(1R,2S,5R)-(−)-menthoxymethylimidazolium salts-based chiral ionic liquids

A new group of imidazolium salt-based chiral ionic liquids have been prepared and characterized. The chiral ionic liquids obtained are stable in air, in contact with water and popular organic solvents. Their physicochemical properties, single-crystal X-ray structures, antimicrobial activities, and antielectrostatic effects have been determined. The chiral ionic liquids synthesized have proven to represent not only potential new solvents in asymmetric synthesis but also effective disinfectants with antielectrostatic activity.     

Enzyme-catalyzed synthesis and absolute configuration of (1S,2R,5S)- and (1R,2S,5R)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile,key intermediates for the preparation of chiral cyclobutane-containing pheromones

Formal synthesis of chiral grandisol and the oleander scale pheromone and their antipodes can be achieved through a convenient lipase-catalyzed enantiodifferentiation process of the common cyclobutane intermediate (±)-2-(1-hydroxyethyl)-1-(methoxymethyloxyethyl)cyclobutane-1-carbonitrile 3. The resolution afforded both enantiomers in almost enantiomerically pure form and their absolute configurations were assigned on the basis of the Δδ values for their (R)- and (S)-MTPA esters.     

Studies towards the synthesis of (1R,2S)- and (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonates and (1S,2S)- and (1R,2S)-2,3-epoxy-1-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1S,2S)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised by the intramolecular Williamson reaction of diethyl (1S,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate. The cis-analogue was obtained as O-ethyl or O,O-diethyl (1R,2S)-1,2-epoxy-3-hydroxypropylphosphonates, when (1R,2R)-1,3-dihydroxy-2-mesyloxypropylphosphonate or its 3-O-trityl derivative were used as starting materials, respectively. The intramolecular Williamson cyclisations of diethyl (1S,2R)- and (1R,2S)-1-benzyloxy-3-hydroxy-2-mesyloxypropylphosphonates led to diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, respectively, with the concomitant formation of diethyl (E)-1-benzyloxy-3-hydroxyprop-1-en-1-phosphonate. From diethyl (1S,2S)- and (1R,2S)-2,3-epoxy-1-benzyloxypropylphosphonates, enantiomerically pure diethyl (1S,2S)- and (1R,2S)-1,2-dihydroxypropylphosphonates were obtained by catalytic hydrogenation, while diethyl (1S,2S)- and (1R,2S)-3-acetamido-1,2-dihydroxypropylphosphonates were produced after epoxide ring opening with dibenzylamine, acetylation and hydrogenolysis.     

Synthesis of chiral 1,5-disubstituted pyrrolidinones via electrophile-induced cyclization of 2-(3-butenyl)oxazolines derived from (1R,2S)- and (1S,2R)-norephedrine

Starting from (1R,2S)- and (1S,2R)-norephedrine, enantiomers of the corresponding 2-(3-butenyl)oxazolines were prepared in a two-step process. The cyclization of the intermediate alkenylamides with phenylselenyl bromide afforded cyclic imidates instead of the expected pyrrolidinones. The electrophile-induced cyclizations of 2-alkenyloxazolines with bromine or iodine produced diastereomeric mixtures of chiral 1,5-disubstituted pyrrolidinones. The ring closure of the all-cis (1R,2S,5R)-diastereomer 7 with NaH resulted in the tetrahydropyrrolo[2,1-b]oxazol-5-one derivative 18, which was alternatively prepared by the cyclocondensation of (1R,2S)-norephedrine with levulinic acid.     

New chiral phosphine-phosphonites derived from (2R,3R)-dimethyl tartrate, (S)-binaphthol and (1R,2S)-ephedrine

The reaction of 2-lithiophenyldiphenylphosphine with phosphorus trichloride afforded the new unsymmetric phosphine, dichloro(2-diphenylphosphinophenyl)phosphine (4). Condensation of 4 with (a) (2R,3R)-dimethyl tartrate or (b) (S)-binaphthol in the presence of triethylamine gave new chiral phosphine-phosphonite ligands, (2R,3R)-[2-(2′-(diphenylphosphino)phenyl)-4,5-bis(carbomethoxy)-1,3,2-dioxaphospholane] ((2R,3R)-5) and (S)-[2-(diphenylphosphino)benzene][1,1′-binaphthalen-2,2′-diyl]phosphonite] ((S)-6). The analogous reaction of 4 with (1R,2S)-ephedrine using N-methylmorpholine as the base, gave [2-(2′-(diphenylphosphino)phenyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine] (7) as a 95:5 mixture of diastereoisomers.     

Enzymatic preparation of (1S,2R)- and (1R,2S)-stereoisomers of 2-halocycloalkanols

The stereoisomers of cis-2-halocycloalkanols were resolved by a kinetically controlled transesterification with vinyl acetate in the presence of lipases in organic media. High enantioselectivities (ee >98%) and good isolated yields were obtained for all substrates using the appropriate lipase. Burkholderia cepacia lipase was the most efficient enzyme for the resolution of these substrates. The enantiomeric purities of the compounds were defined by derivatization with Mosher’s acid and the absolute configurations were determined by chemical correlation.     

Preparation of Optically Pure (1R, 2S)- and (1S, 2R)-DI-p-Methoxyphenyl Amino Alcohol

Racemic di-p-methoxyphenyl amino alcohol was synthesized in three steps. Optically pure di-p-methoxyphenyl amino alcohols were obtained by recrystallization. The absolute configuration of the amino alcohol was determined by X-ray crystallography.     

(R,R)-2,3-Butanediol and (s)-pinanediol allylboronates in chiral synthesis of (2S,3S)-3-methyl-5-hexen-2-ol

(R,R)-Butanediol (dichloromethyl)boronate ( 1 ) with 1 equiv. allylmagnesium halide yields (R,R)-2,3-butanediol (1S)-(1-chloro-3-butenyl)boronate ( 3 ) together with the diallylated product (R,R)-2,3-butanediol (1-allyl-3-butenyl)boronate ( 4 ). The formation of 4 is unprecedented in reactions of α-chloroboronic esters with Grignard reagents. With methylmagnesium bromide 3 yielded (R,R)-2,3-butanediol (1S)-(1-methyl-3-butenyl)boronate ( 5 ), which failed to hydrolyze with water. Hydrolysis of 3 yielded impure α-chloroboronic acid, which was esterified with pinacol and treated with methylmagnesium bromide to form 6 , which with (dichloromethyl)lithium followed by methylmagnesium bromide yielded diastereomeric boronic esters 7 and 8 . Oxidation by hydrogen peroxide yielded (2S,3S)- and (2R,3S)-3-methyl-5-hexen-2-ol ( 9 and 10 , ees unknown). Treatment of (s)-pinanediol allylboronate ( 11 ) with (dichloromethyl)lithium at −100°C followed by zinc chloride at up to 25°C has proceeded in the normal way to form (s)-pinanediol (1S)-(1-chloro-3-butenyl)-boronate ( 12 ), which has been elaborated via 13 , 14 , and 15 to (2S,3S)-3-methyl-5-hexen-2-ol ( 9 ) in 95% de.     

(-)-(1R,2S)-肉豆蔻木脂素的不对称合成

报道了天然产物(-)-肉豆蔻木脂素的全合成. 以香草醛为起始原料, 经Wittig反应、LiAlH₄还原和Sharplass不对称双羟化等反应构建了苏式结构的中间体; 以焦性没食子酸为原料, 经Claisen重排反应制得另一种苯丙素片段; 2个中间体通过Mitsunobu反应, 缩合并使构型翻转, 得到赤式-(-)-肉豆蔻木脂素. 为赤式8-O-4′新木脂素的合成提供了一种新方法.     

Heterotricyclodecane XX (+)-(1S, 3S, 6S, 8S)- und (−)-(1R, 3R, 6R, 8R)-2, 7-Dioxa-twista-4,9-dien

(+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene. A synthesis and the determination of the sense of chirality of (+)-(1S, 3S, 6S, 8S)- and (?)-(1R, 3R, 6R, 8R)-2,7-dioxa-twista-4,9-diene ((+)- 5 and (?)- 5 , respectively) is described.     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.     

手性5-(R)-(1′R,2′S,5′R)-孟氧基丁内酯并[3,4-b]-2(S)-6(R)-1-N-环己基氮杂环丙烷的合成及晶体结构

环己胺与手性元5-(R)-(1′R,2′S,5′R)-孟氧基-3-溴-2(5H)-呋喃酮的不对称M ichael加成/分子内亲核取代反应,得到含有两个新手性中心的氮杂环丙烷/稠合丁内酯标题化合物。对其进行了谱学表征和X-射线单晶衍射测定。标题化合物分子式为C20H33NO3,M r=335.47,三斜晶系,P1空间群,晶胞参数:a=5.438(11)。A,b=8.117(2)。A,c=11.572(2)。A,α=96.84(3)°,β=94.48(3)°,γ=101.86(3),°V=493.5(2)。A3,Z=1,D c=1.129g/cm3,R=0.0867,wR=0.2344。