Remote stereocontrol by the sulfinyl group: Mukaiyama aldol reactions of (S)-2-[2-(p-tolylsulfinyl)phenyl]acetaldehyde in the asymmetric synthesis of β-hydroxyacids and 1,3-diols

(S)-2-[2-(p-Tolylsulfinyl)phenyl]acetaldehyde reacts with different O-silylated ketenethioacetals in the presence of Yb(OTf)₃ yielding β-hydroxythioesters in high yields and diastereoselectivities. The obtained compounds were readily transformed into β-hydroxyacids and their corresponding diols. These Mukaiyama aldol reactions are a direct evidence of the ability of the sulfinyl group to control 1,5- and 1,6-asymmetric induction processes.     

Remote stereocontrol by sulfinyl groups: asymmetric alkylation of chiral 2-p-tolylsulfinyl benzyl carbanions

Alkylation reactions of the benzyllithiums derived from enantiomerically pure 2-p-tolylsulfinyl alkylbenzenes have been carried out with excellent yields and high de. A lithiation-substitution sequence, stereochemically controlled by a remote sulfoxide, accounts for the experimental results.     

手性氨基醇（R）－2－氨基－1，1－二苯基－3－（2－萘基）－1－丙醇：制备及其对前手性酮硼烷还原的对映选择性催化作用

用丙二酸酯法合成了Ｎ－乙酰基－３－（２－萘基）－ＤＬ－α－丙氨酸乙酯３．３经酶法拆分，得光学活性的Ｄ－３，后者经盐酸水解、酯化后再与苯基溴化镁作用，制得标题化合物６。在０．５ｍｍｏｌ６存在下，用过量硼烷对一系列前手性酮还原，得到了相应的光学活性二级醇。对映体过量（ｅ．ｅ值）５７．０～１００％。     

Dynamic kinetic transformation of sulfinyl chlorides: synthesis of enantiomerically pure C(2)-symmetric bis-sulfoxides.

Two modular and highly convergent approaches for the synthesis of both isomers of a large number of optically pure C(2)-symmetric bis-sulfoxides have been developed, and their scope and limitations have been assessed. The first one uses as intermediate diastereomerically pure C(2)-symmetric bis-sulfinate esters 6(S(S),S(S)) and 6(R(S),R(S)), obtained by dynamic kinetic resolution of ethane-1,2-bis-sulfinyl chloride 5. A single inducer of chirality, the glucose-derived DAG (diacetone-D-glucose) 1 is used for the enantioselective synthesis of both diastereomerically pure C(2)-symmetric bis-sulfinate esters, thanks to the opposite stereodirecting effect of pyridine and (i)Pr(2)NEt used to catalyze the reaction. The second approach is based on the copper-catalyzed oxidative coupling of optically pure lithiomethyl sulfoxides. Both isomers of a large number of methyl sulfoxides can be obtained in a convergent manner using (R(S))- and (S(S))-DAG methanesulfinate esters 8R(S) and 8S(S). Methanesulfinates 8R(S) and 8S(S) are also obtained in an enantioselective way by a dynamic kinetic resolution of methane sulfinyl chloride 24. The final bis-sulfoxides are obtained with enhanced enantioselectivities compared to the corresponding monomers, as a result of the Horeau effect which is operating in both approaches. A model based on the formation of pentacoordinated sulfur intermediate is proposed. This model can explain the dynamic kinetic resolution observed via Berry pseudorotations, without the commonly accepted in situ racemization of the starting material. The usefulness of the approaches is demonstrated by the preparation of complexes of Pd(II) and Ru(II) bearing bidentated chiral sulfoxides as ligands.     

An auxiliary induced asymmetric synthesis of functionalized cyclobutanes by means of catalytic (2+2)-cycloaddition reaction

A new entry to optically active hydroxycyclobutanes is described. Treatment of silyl enol ether and (−)-8-phenylmenthyl acrylate in the presence of a catalytic amount of EtAlCl₂ affords enantiomerically enriched multi-substituted cyclobutane compounds in a good yield and diastereofacial selectivity.     

Enantioselective synthesis of axially chiral 1-(1-naphthyl)isoquinolines and 2-(1-naphthyl)pyridines through sulfoxide ligand coupling reactions

Racemic 1-(1′-isoquinolinyl)-2-naphthalenemethanol rac-12 was prepared through a ligand coupling reaction of racemic 1-(tert-butylsulfinyl)isoquinoline rac-7 with the 1-naphthyl Grignard reagent 10. Resolution of rac-12 was achieved through chromatographic separation of the Noe-lactol derivatives 14 and 15, providing (R)-(−)-12 of >99% ee and (S)-(+)-12 of 90% ee. The ligand coupling reaction of optically enriched sulfoxide (S)-(−)-7 (62% ee) with Grignard reagent 10 furnished rac-12, with the absence of stereoinduction resulting from competing rapid racemisation of the sulfoxide 7. Reaction of optically enriched (S)-(−)-7 with 2-methoxy-1-naphthylmagnesium bromide was also accompanied by racemisation of the sulfoxide 7, and furnished optically active (+)-1-(2′-methoxy-1′-naphthyl)isoquinoline (+)-3b in low enantiomeric purity (14% ee). The absolute configuration of (+)-3b was assigned as R using circular dichroism spectroscopy, correcting an earlier assignment based on the Bijvoet method, but in the absence of heavy atoms. Optically active 2-pyridyl sulfoxides were found not to undergo racemisation analogous to the 1-isoquinolinyl sulfoxide 7, with the ligand coupling reactions of (R)-(+)- and (S)-(−)-2-[(4′-methylphenyl)sulfinyl]-3-methylpyridines, (R)-(+)-17 and (S)-(−)-17, with 2-methoxy-1-naphthylmagnesium bromide providing (−)- and (+)-2-(2′-methoxy-1′-naphthyl)-3-methylpyridines, (−)-18 and (+)-18, in 53 and 60% ee, respectively. The free energy barriers to internal rotation in 3b and 18 have been determined, and the isoquinoline (R)-(−)-12 examined as a ligand in the enantioselectively catalysed addition of diethylzinc to benzaldehyde; (R)-(−)-12 was also converted to (R)-(−)-N,N-dimethyl-1-(1′-isoquinolinyl)-2-naphthalenemethanamine (R)-(−)-19, and this examined as a ligand in the enantioselective Pd-catalysed allylic substitution of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.     

Preparation of enantiomerically pure (R)-2-butyryloxymethylglycidol by lipase-catalyzed asymmetric hydrolysis

Optically active epoxy alcohol, (R)-2-butyryloxymethylglycidol3 which is the precursor of a tert-alcohol chiral building block was obtained in high enantiomeric purity, 98.7% e.e., by lipase-catalyzed asymmetric hydrolysis using a phosphate buffer and organic co-solvent system in 95% of chemical yield.     

1-(2-Pyridyl)-2-propen-1-ol: a multipurpose reagent in organic synthesis

A peculiar thermal behaviour of hydroxyallylpyridyl derivatives, likely associated to the weak acidity of the ‘picoline-type’ hydrogen atom and responsible for the formation of allyl inversion products, has been reported. The ‘mobility’ of the same hydrogen atom allowed the unprotected title compound to behave regioselectively as C-1, C-2 or C-3 carbon nucleophile depending on the thermal or base-promoted experimental conditions and on the kind of electrophile; moreover, the corresponding Hantzsch-type pyridine tautomer displayed a biomimetic ability to transfer hydrogen to aromatic and heteroaromatic nitro derivatives.     

Tuning the helical twisting power of nematic liquid crystals induced by chiral 1, 2-propanediol derivatives using varied substituents

In this study,a novel series of chiral 1,2-propanediol derivatives with different electron-donating and electron-withdrawing groups were synthesized and characterized by FT-IR and ~1H NMR.The helical twisting properties of all the chiral dopants were investigated by doping the chiral dopants into a nematic liquid crystal host(SLC-1717).The results indicate that the donor-acceptor electron effect have a prominent influence on helical twisting property of the chiral nematic phase induced by the chiral dopants. Introducing electron-withdrawing groups into the terminal ends of chiral 1,2-propanediol can decrease the absolute values of the helical twisting power.In addition,the helix inversion temperatures of the induced chiral nematic phase are variational with the change of terminal groups.     

Comparison of the chiral resolution on cis-trans isomeric chiral stationary phases derived from (S)-1-(1-naphthyl)ethylamine

A pair of cis-trans isomeric chiral stationary phases (CSPs) derived from (S)-1-(1-naphtyl)ethylamine was prepared. The chromatographic behaviours on both CSPs with regard to the resolution of enantiomeric amino acids, amino alcohols, amines, and carboxylic acid were studied. According to separation factors, the trans-CSP showed better chiral recognition ability for the separation of most analytes chosen in this study. Three homologous series of the alkyl esters of racemic amino acids were resolved on both CSPs using n-hexane-2-propanol and n-hexane-dichloromethane as mobile phases. The trans-CSP also showed better enantioselectivity for the resolution of homologues. A reverse of elution order was observed for the resolution of the homologous series of phenylglycine alkyl esters on both CSPs. It was found that the relationship between the separation factor and the alkyl chain length of the ester homologous series depended upon the components of mobile phase. A higher magnitude of difference between the two CSPs in enantioselectivity for the resolution of a given homologue was obtained when n-hexane-dichloromethane was used as a mobile phase. A chiral recognition process, in which steric repulsion, face-to-face π-π interaction, face-to-edge π-π interaction and hydrogen bonding interaction were involved, was also suggested to describe the separation of enantiomeric homologues on both CSPs. This study clearly indicates that the chiral resolution is influenced by the geometry of the double bond in a CSP.     

A facile synthesis of 2-substituted-2,3-dihydro-4(1H)-quinazolinones in 2,2,2-trifluoroethanol

2-Substituted-2,3-dihydro-4(1H)-quinazolinones were obtained in high yields by condensation of anthranilamide with aryl, alkyl or heteroaryl aldehydes or ketones in the refluxing 2,2,2-trifluoroethanol without any catalyst.     

A tandem asymmetric synthesis approach for the efficient preparation of enantiomerically pure 9-(hydroxyethyl) anthracene

A tandem approach for the preparation of gram quantities of enantiomerically pure 9-(hydroxyethyl)-anthracene is presented using an asymmetric reduction followed by kinetic resolution that has potential applicability to other chiral alcohols.     

Synthesis of enantiomerically pure 2-(N-aryl,N-alkyl-aminomethyl)aziridines: a new class of ligands for highly enantioselective asymmetric synthesis

A simple and effective synthesis of enantiomerically pure 2-(N-aryl-, N-alkyl-aminomethyl)aziridines from (2S)-N-tritylaziridine-2-carboxylic acid methyl ester has been developed. Treating of this key ester with several primary and secondary amines in the presence of AlMe₃ provided the corresponding chiral N-trityl-2-carboxamides, and their reduction performed with different reagents resulted in the formation of the expected 2-(aminomethyl)aziridines. The choice of reaction conditions allows to either keep or leave the trityl substituent in the product. Such 2-(aminoalkyl)aziridines have shown very high catalytic efficiency in the asymmetric arylation of aldehydes and in other testing asymmetric reactions. On the other hand, homochiral N-trityl-2-carboxamides are interesting building blocks for the synthesis of various biologically active compounds.     

掌性5-(1-孟氧基)-3,4-二溴-2-(5H)-呋喃酮的光学片合成及新的串联不对称Michael加成消除反应

手性γ-孟氧基丁烯酸交酯在构成各种杂环化合牧天然产物中起重要作用.本文报道了一些新的γ-孟氧基丁烯交酯的新的手性源的制备和研究了它们的不对称反应.     

An efficient approach to the synthesis of enantiomerically pure trans-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids

The synthesis of (1R,2S)- and (1S,2R)-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids was accomplished using different strategies. The (1R,2S)-stereoisomer could be efficiently obtained by the cyclopropanation of ethyl diethoxyphosphorylacetate with the cyclic sulfate derived from (S)-3-benzyloxy-1,2-propandiol as a key step. The (1S,2R)-stereoisomer was synthesized from a readily available (1S,5R)-3-oxabicyclo[3.1.0]hexan-2-on-1-phosphonate.     

High-performance liquid chromatographic resolution of 1-(1,4-benzodioxane-2-formyl)-piperazine enantiomers after chiral derivatization

Chiral separation of racemic mixtures is of the greatest importance to the pharmaceutical industry, as the isomers of a given racemate may exhibit substantially different pharmacological effects, not to mention possibly differing toxicity behaviour. A novel chiral separation method is developed for the determination of 1-(1,4-benzodioxane-2-formyl)piperazine (BFP) enantiomers. The indirect resolution is performed by applying precolumn derivatization with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The resulting diastereoisomers are separated on a reversed-phase ODS column with methanol-potassium dihydrogen phosphate (0.02mol/L, 50:50) as mobile phase. UV detection is at 250 nm. The effect of mobile phase composition upon resolution and analysis time is investigated. Two diastereoisomers show nearly base-line separation under optimal chromatographic conditions. The presented study provides a simple and accurate method for the enantiomeric quality control and the optical purity assay of BFP.     

Some new C2-symmetric bicyclo[2.2.1]heptadiene ligands: synthesis and catalytic activity in rhodium(I)-catalyzed asymmetric 1,4- and 1,2-additions

C₂-Symmetric bicyclo[2.2.1]hepta-2,5-dienes with various substituents (R=Bn, i-Bu, c-Hex, allyl) are prepared starting from the corresponding enantiomerically pure bis-triflate (R=OTf). These chiral ligands are tested and compared in rhodium(I)-catalyzed 1,4- and 1,2-addition of phenylboronic acid to cyclic enones and aryl aldehydes, respectively. Some interesting reactivity and selectivity effects due to the introduction of sterically demanding or olefinic substituents are reported. Moreover, remarkably high catalytic activity is observed for the rhodium(I)-catalyzed 1,2-addition.     

New synthesis of enantiomerically pure (S)-3-amino-2-phenyl propanoic acid via the asymmetric transformation of its racemic N-phthaloyl derivative

The synthesis of racemic N-phthalyl 3-amino-2-phenyl propanoic acid and its asymmetric transformation via the corresponding prochiral ketene have been investigated, allowing the preparation of enantiomerically pure (S)-3-amino-2-phenyl propanoic acid.     

Asymmetric synthesis of 1,2-bis(diphenylphosphino)-1-phenylethane via a chiral palladium template promoted hydrophosphination reaction

An organopalladium(II) complex derived from (S)-N,N-dimethyl-1-(1-naphthyl)-ethylamine was employed as the chiral auxiliary to promote the asymmetric hydrophosphination reactions between diphenylphosphine and (E) or (Z)-diphenylphosphinostyrene in high regio- and stereoselectivities at low temperature with triethyl amine as external base. Optically active free ligand (R)-1,2-bis(diphenylphosphino)-1-phenylethane was obtained in high yield subsequently. Mechanistic pathways explaining the stereoselectivity of the chiral organopalladium template promoted hydrophosphination reactions are also proposed.