Asymmetric synthesis of (-)-indolizidines 167B and 209D based on stereocontrolled allylation of a chiral tricyclic N-acyl-N,O-acetal

[reaction: see text] The tricyclic N-acyl-N,O-acetal incorporating (S)-2-(1-aminoethyl)phenol as a chiral auxiliary underwent TiCl4-mediated allylation to give the chiral (5S)-allylpyrrolidinone with retention of configuration in high yield and diastereoselectivity. On the bases of this methodology, the asymmetric syntheses of the dendrobatid alkaloids (-)-indolizidines 167B and 209D were achieved.     

Asymmetric addition of dimethylzinc to N-tosylarylimines catalyzed by a rhodium-diene complex toward the synthesis of chiral 1-arylethylamines

[STRUCTURE: SEE TEXT] A rhodium complex coordinated with a chiral diene, (R,R)-2,5-diphenylbicyclo[2.2.2]octa-2,5-diene (Ph-bod), catalyzed the asymmetric addition of dimethylzinc to N-tosylarylimines to give high yields of chiral 1-aryl-1-ethylamines with high enantioselectivity (94-98% ee).     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

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.     

Catalytic asymmetric synthesis of alpha,alpha,alpha-trifluoromethylamines by the copper-catalyzed nucleophilic addition of diorganozinc reagents to imines

[reaction: see text] A copper-catalyzed asymmetric addition of diorganozinc reagents to N-phosphinoylimines has been developed for the synthesis of chiral alpha,alpha,alpha-trifluoromethylamines. The trifluoromethyl ketimines, generated in situ from the corresponding hemiaminals, led to the chiral amides in high yields (71-89%) and excellent enantiocontrol (91-99% ee).     

Chiral hetero Diels-Alder products by enantioselective and diastereoselective zirconium catalysis. Scope,limitation, mechanism,and application to the concise synthesis of (+)-Prelactone C and (+)-9-deoxygoniopypyrone

Catalytic asymmetric hetero Diels-Alder (HDA) reactions using a chiral zirconium complex have been developed. The reactions of aldehydes with Danishefsky's dienes proceeded smoothly to afford the corresponding pyranone derivatives in high yields with high diastereo- and enantioselectivities in the presence of a chiral zirconium complex, which was prepared from zirconium tert-butoxide, (R)-3,3'-diiodobinaphthol or its derivative, a primary alcohol, and a small amount of water. It is noted that 2,3-trans-pyranone derivatives were obtained with remarkably high diastereo- and enantioselectivities in the reaction with 4-methyl Danishefsky's diene. This is the first example of catalytic asymmetric trans-selective hetero Diels-Alder reactions of aldehydes. Furthermore, asymmetric HDA reactions with 4-benzyloxy Danishefsky's dienes were conducted to afford 2,3-cis-pyranone derivatives in high selectivities. Isolation of an intermediate of this asymmetric hetero Diels-Alder reaction indicated that the reaction proceeded in a stepwise cycloaddition pathway. Finally, these catalytic, asymmetric hetero Diels-Alder reactions were successfully applied to concise syntheses of biologically important natural pyranone derivatives, (+)-Prelactone C and (+)-9-deoxygoniopypyrone.     

Synthesis of novel bidentate P-chiral diaminophosphine oxide preligands: application to Pd-catalyzed asymmetric allylic substitution reactions

We developed a novel (S)-L-phenylalanine derived-bidentate chiral diaminophosphine oxide (DIAPHOX) preligand (S,S(P))-9b, which was successfully applied to Pd-catalyzed asymmetric allylic alkylation and amination. Using the Pd-(S,S(P))-9b catalyst system, asymmetric allylic alkylation and amination proceeded very smoothly, affording the corresponding products in excellent yield with high enantiomeric excess. It is noteworthy that both enantiomers were accessible with high enantiomeric purity using the structurally related DIAPHOX preligands (S,S(P))-9b and a monodentate chiral diaminophosphine oxide preligand (S,R(P))-10a, both of which can be prepared from a single chiral source, (S)-L-phenylalanine.     

Improved and efficient synthesis of chiral N,P-ligands via cyclic sulfamidates for asymmetric addition of butyllithium to benzaldehyde

A robust and scaleable route to chiral 1-isopropylamino-2-(diphenylphosphino)ethanes is described via the ring-opening of chiral, cyclic sulfamidates with potassium diphenylphosphide (KPPh(2)). The novel protocol offers a robust access to gram quantities of chiral amino phosphinoethanes in high yields. The Li-amides of the chiral aminophosphines were evaluated as chiral ligands in the asymmetric addition of n-butyllithium (BuLi) to benzaldehyde, yielding 1-phenylpentanol up to 98% ee.     

Asymmetric total synthesis of (+)-curcutetraol and (+)-sydonol

The asymmetric total syntheses of (+)-curcutetraol and (+)-sydonol, phenolic bisabolane-type sesquiterpenoids having chiral tertiary alcohol moiety in the o-position of a phenol, were achieved in high enantiomeric excesses (99% ee). The chiral tertiary benzylic alcohol moiety of these compounds was constructed by an asymmetric synthesis using an easily available chiral aminal, (−)-(2R,5S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane. The absolute configurations of both (+)-curcutetraol and (+)-sydonol have been assumed to be S-configuration based on the stereochemical course of the well established asymmetric synthesis used in the syntheses.     

Chiral binaphthylthiophosphoramide-cu(I)-catalyzed asymmetric addition of diethylzinc to N-sulfonylimines

In the presence of a catalytic amount of chiral binaphthylthiophosphoramide L2 (6 mol %) and Cu(I) (3 mol %), the asymmetric addition of diethylzinc to N-sulfonylimines could be achieved in good yields with moderate to high ee (63-93% ee) at 0 degrees C in toluene. A novel chiral binaphthylthiophosphoramide ligand system for this asymmetric addition reaction has been explored.     

(S)-3-羟基四氢呋喃的合成研究进展

综述了(S)-3-羟基四氢呋喃制备方法的研究现状,重点阐述了三种合成方法：（1）手性底物合成法;（2）手性催化剂不对称合成法;（3）酶催化不对称合成法。分析了不同制备方法的优劣,并对其未来发展进行了展望。参考文献45篇。     

Synthesis of 7,7’-Disubstituted BINAP and Their Application in Asymmetric Catalytic Reaction

The design of new chiral ligands plays a very important role in the development of transition metal catalyzed asymmetric synthesis. Many chiral diphosphine ligands have been prepared and applied in asymmetric catalytic reactions with excellent enantioselectivities. Among the chiral diphosphine ligands reported, BINAP was found to have been the widest application in the transition metal catalyzed reaction. Recently we have developed a novel oxovanadium (Ⅳ) complex catalyst for the oxidative …     

R-沙美特罗的合成方法

近年来手性沙美特罗的合成方法有微生物催化、不对称氢化、CBS(Corey-Bakshi-Shibata)还原反应及不对称Henry反应、手性(Salen)Co试剂催化的HKR(末端环氧不对称水解动力学)拆分反应等。对这些方法进行比较,结果表明,不对称催化合成由于其反应收率高、反应产物光学纯度高、操作容易控制,在目前手性药物的合成中处于主导地位。此外酶催化不对称合成、手性辅基诱导的对映选择性合成等方法也是有效的途径。     

Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid

The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).     

Catalytic asymmetric allylation of aldehydes and related reactions with bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as a mu-oxo-type chiral Lewis acid

A new, chiral bis-Ti(IV) oxide of type 3 has been designed and can be utilized for strong activation of aldehyde carbonyls, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin. The chiral bis-Ti(IV) catalyst (S,S)-3 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide with (S)-BINOL or by treatment of ((S)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. Treatment of hydrocinnamaldehyde with allyltributyltin under the influence of chiral bis-Ti(IV) oxide (S,S)-3 generated in situ (10 mol %) in CH(2)Cl(2) afforded an allylation product in 84 % yield and with 99 % ee. This asymmetric allylation with non-racemic bis-Ti(IV) oxide 3 and partially resolved (S)-BINOL shows a positive nonlinear effect in correlation of the enantiopurity of the allylation product with the ee of the (S)-BINOL. Chiral bis-Ti(IV) oxide (S,S)-3 can also be utilized for related reactions such as asymmetric methallylation and propargylation of aldehydes with high enantioselectivity. This asymmetric approach provides a very useful way of obtaining high reactivity and selectivity through the simple introduction of the M-O-M unit into the design of chiral Lewis acid catalysts.     

Synthesis of a new chiral nonracemic C(2)-symmetric 2,2'-bipyridyl ligand and its application in copper(I)-catalyzed enantioselective cyclopropanation reactions

An efficient synthesis of a low molecular weight, chiral nonracemic and C(2)-symmetric bipyridyl ligand is reported. The ligand was prepared using a catalytic asymmetric dihydroxylation reaction of a pyrindine as a key step. The ligand was evaluated in the asymmetric copper(I)-catalyzed cyclopropanation reactions of a series of alkenes and diazoesters. Very high diastereoselectivities and enantioselectivities were observed (>95:5 dr and up to 99% ee). These are the highest reported stereoselectivities for a chiral bipyridyl ligand. [structure: see text]     

1,6-Asymmetric induction during the conjugate addition of arylcopper reagents to a chiral sulfinyl-substituted pyrrolyl alpha,beta-unsaturated amide.

The asymmetric conjugate addition of arylcopper reagents derived from aryl Grignard reagents and copper(I) iodide to a chiral 1-[2-(p-tolylsulfinyl)]pyrrolyl cinnamide proceeded smoothly to give (3R)-adducts with high diastereoselectivities (> or =92% de) in high yields. Conjugate additions either of the cinnamide with the alkyl Grignard reagent-copper(l) iodide combination or of the crotonamide derivative with aryl Grignard reagent-copper(l) iodide gave moderate to good diastereoselectivities. With these sulfinyl pyrrolyl alpha,beta-unsaturated amides, the chiral auxiliary was efficiently recovered without any loss of optical purity after asymmetric conjugate addition.     

C(2)-Symmetric bis-sulfoxide: A novel chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols

A new heterocyclic compound, C(2)-symmetric bis-sulfoxide 1, has been found to be an efficient chiral auxiliary for asymmetric desymmetrization of cyclic meso-1,2-diols via diastereoselective acetal fission. Both (R,R)- and (S,S)-1 are readily synthesized with high optical purity via asymmetric oxidation of 1, 5-benzodithiepan-3-one (2). After acetalization of meso-1,2-diols 6a-e and a mono-TMS ether 6f with this chiral auxiliary 1, the resulting acetals 7a-f were subjected to base-promoted acetal fission upon treatment with potassium hexamethyldisilazide (KHMDS) followed by acetylation or benzylation to give the desymmetrized diol derivatives 8a-f with high diastereoselectivity. The chiral auxiliary 1 is readily removed by acid-promoted hydrolysis and can be recovered without a loss in enantiomeric excess.     

Rh-catalyzed asymmetric hydrogenation of gamma-phthalimido-substituted alpha,beta-unsaturated carboxylic acid esters: an efficient enantioselective synthesis of beta-aryl-gamma-amino acids

A series of chiral beta-aryl-gamma-amino acid ester derivatives were synthesized in high enantioselectivities (93-97% ee) via the Rh-catalyzed asymmetric hydrogenation of gamma-phthalimido-alpha,beta-unsaturated carboxylic acid esters using highly modular chiral BoPhoz-type phosphine-aminophosphine ligands. The method has been applied successfully to the synthesis of several chiral pharmaceuticals including (R)-baclofen and (R)-rolipram with high enantioselectivities.     

Application of phosphine-oxazoline ligands in Ir-catalyzed asymmetric hydrogenation of acyclic aromatic N-arylimines

[reaction: see text] A new class of chiral phosphine-oxazoline ligands have been developed. Chiral Ir complexes prepared from these ligands induced high enantioselectivities (66-90% ee) when applied to the asymmetric hydrogenation of acyclic aromatic N-arylimines.