Asymmetric induction—V : Effect of R on asymmetric induction in additions to abcC-COR compounds

The diastereomeric product ratios from reactions involving the addition of various reagents to the carbonyl of φCH₃HC-COR compounds varies over a wide range. This variation is interpreted as due partly to changes in the structure of the diastereomeric transition states with changes in the size of R. For example, when R is smaller than the φCH₃HC group the diastereomeric product ratios are close to those predicted on the assumption that 1 and 2 are the minimum energy diastereomeric transition states; and when R is larger than the φCH₃HC group, the diastereomeric product ratios are large and closer to those that one might expect if 5 and 6 were the minimum energy transition states.     

Asymmetric reductions of propargyl ketones : An effective approach to the synthesis of optically-active compounds

Propargyl ketones are readily reduced by the asymmetric reducing agent B-3-pinanyl-9- borabicyclo[3.3.1]-nonane (Alpine-borane). The reagent prepared from (+)-α-pinene and 9-BBN provides the R enantiomer while the S enantiomer can be obtained from (-)-α-pinene. Alternatively the S enantiomer can be prepared from the reagent derived from 9-BBN and the benzyl ether of nopol (6,6-dimethyl-bicyclo[3.11.]hept-2-ene-2-ethanol). The limiting factor in obtaining high enantiomeric induction is often the enantiomeric purity of the α-pinene. With 100% enantiomerically pure α-pinene, propargyl alcohols of essentially 100% ee can be obtained. A predictive rationalization of the transition state leading to this remarkable selection is presented. The acetylene unit of the propargyl alcohol provides a convenient handle for transformations to other useful, optically-active products. The use of propargyl alcohols for the synthesis of optically-active α- and β-substituted γ-lactones, and δ-lactones is illustrated     

Electrochemical cleavage of bridged C-C bonds in bicyclic enol ethers and monooxa- and dioxabicycloalkanes: An approach to macrocyclic compounds

Electrolysis of bicyclic enol ethers in methanol results in their electrochemical mono-and dimethoxylation. Electrolysis of monooxa-and dioxabicycloalkanes leads to the electrochemical cleavage of their bridged C-C bonds and electrooxidative conversion into esters of Ω-(2-methoxytetrahydrofuryl)-, Ω-(dimethoxymethyl)-, and Ω-(l,3-dioxalan-2-yl) alkanoic acids.     

Self-assembly of achiral and chiral macrocyclic ligands: synthesis,protonation constants,conformation and asymmetric catalysis

New 30-membered achiral and chiral polyaza macrocyclic ligands, L1 and L2 were synthesized directly from [3 + 3] condensation of phthalic dicarboxaldehyde with cis- and (1R,2R)-diaminocyclohexane, respectively. The trimeric macrocyclic structures were confirmed by electrospray ionization mass spectrometry (ESI-MS), 1H NMR, 13C NMR spectroscopy and elemental analysis. Potentiometry was used to determine the protonation constants of the ligands. UV-vis spectrophotometric titration was employed to investigate the coordination and conformational properties of the chiral ligand (L2). Direct enantioselective aldol reaction has been successfully performed using 4-nitrobenzaldehyde and acetone in the presence of the chiral macrocycle and its zinc(II) complexes as catalysts.     

An asymmetric approach to the synthesis of trans-dihydrindandione

A three-step asymmetric approach to the synthesis of (3aS,7aS)-3a,4-dihydro-7a-methyl-1,5(7aH)-indandione in 60% enantiomeric excess is described.     

An approach to an asymmetric synthesis of stemofoline

A stereoselective Mannich reaction between an (S)-tert-butylsulfinimine and methyl (S)-4-benzyloxy-3-methylbutanoate followed by treatment with acid and N-protection was used to prepare methyl (2R,3S)-2-[(S)-2-benzyloxy-1-methylethyl]-3-tert-butoxycarbonylamino-6-methylenedecanoate. This was taken through to methyl (4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-5-tert-butoxycarbonylamino-3,8-dioxododecanoate which on treatment with trifluoroacetic acid cyclised stereoselectively to give (1R,2S,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-tert-butoxycarbonyl-3-oxo-8-azabicyclo[3.2.1]octane, a potential precursor of stemofoline. Reduction and N-deprotection of this ketone gave (1R,2S,3R,4R,5S)-4-[(S)-2-benzyloxy-1-methylethyl]-1-butyl-2-methoxycarbonyl-8-azabicyclo[3.2.1]octan-3-ol the structure of which was confirmed by X-ray diffraction.     

An asymmetric approach to spirocylic systems: a formal synthesis of zizaene

A general route to enantiopure spirocarbocycles is described. The use of various chiral bicyclic lactams 1 that have been doubly alkylated with olefinic halides gives good yields of alpha,alpha-disubstituted chiral lactams 2 which were cyclized to spiro-olefins using ring closure metathesis methodology (Grubbs' catalyst). These spirolactams 3, formed in generally excellent yields, were shown to be smoothly transformed into spirocyclopentenone 6, spirocyclohexenone, 7, and spirolactams 8. Further demonstration of this spirocyclization methodology was featured in a formal synthesis of zizaene, by preparing in enantiomeric form the Coates' intermediate 21. This synthetic effort provided additional examples of the synthetic versatility of chiral bicyclic lactams 2a,b.     

Cyclopiperazines: A new approach to chiral macrocyclic receptors

The synthesis and preliminary substrate binding properties of a series of piperazine-containing macrocycles are described.     

Total synthesis of (+)-pedamide. A new,remote controlled asymmetric induction

Total synthesis of optically active pedamide $\text{2}$, one of the tetrahydropyran moieties of the potent insect poison pederine $\text{1}$, was achieved by employing a new, remote controlled asymmetric reduction of a ketone as key step.     

Chromium complexed carbinols as highly effective auxiliaries for use in asymmetric induction : reduction of α-ketoesters

High percentages of asymmetric induction are obtained during reduction of pyruvate and phenylglyoxylate esters of chromium complexed carbinol $\text{1a}$: 75% with NaBH₄ and 85% to 90% with L-selectride.     

Biomimetic synthesis of (+/-)-galanthamine and asymmetric synthesis of (-)-galanthamine using remote asymmetric induction

(+/-)-Galanthamine (1) was synthesized in excellent yield by applying PIFA-mediated oxidative phenol coupling of N-(4-hydroxy)phenethyl-N-(3',4',5'-trialkoxy)benzyl formamide (15b) as a key step. Because of the symmetrical characteristics of the pyrogallol moiety in the substrate (15b), the phenol coupling resulted in a sole coupling product except for volatile components from the oxidizing agent. On the basis of the successful results of the above strategy, (-)-galanthamine (1) was synthesized by employing a novel remote asymmetric induction, where conformation of the seven-membered ring in the product of the phenol coupling was restricted by forming a fused-chiral imidazolidinone ring with D-phenylalanine on the benzylic C-N bond of the tri-O-alkylated gallyl amino moiety. The conformational restriction and successive debenzylation of the protected hydroxyl groups on the pyrogallol ring caused diastereoselective cyclization to yield a cyclic ether having the desired stereochemistry for the synthesis of (-)-1.     

Thermodynamic asymmetric induction: a new approach to the development of rules for the determination of absolute configurations

The absolute configurations of chiral primary amines can be determined using the optical rotations of the corresponding N-p-toluenesulfonyl-N-2,4-dinitrobenzensulfenyl derivatives.     

Studies toward the synthesis of phomactin A. An approach to the macrocyclic core

An approach to the macrocyclic core of phomactin A is described. Central to this strategy is the use of a cis-fused oxadecalin intermediate, prepared using the dihydropyrone Diels-Alder reaction. The conformational bias inherent to this system is then used to facilitate macrocycle formation via an intramolecular B-alkyl Suzuki coupling.     

新型手性环状胺膦配体的设计合成及在酮的不对称还原中的应用

新型手性配体的设计合成是不对称催化研究的重要内容,其中手性胺膦配体因同时含有"软"的磷原子和"硬"的氮原子而具有丰富的配位化学性能和优秀的不对称诱导能力.本文总结了本研究组最近设计合成的手性环状胺膦配体的制备、表征及其在铁催化酮的不对称还原中的应用.手性1,2-环己二胺与双(2-甲酰基苯基)苯基膦通过[2+2]环缩合反应能够顺利获得手性22元环的亚胺膦配体21,该配体经Na BH4还原后生成大环胺膦配体22.利用手性大环胺膦配体22与Fe3(CO)12原位生成的催化体系,能够高活性、高对映选择性地实现包括杂环芳香酮在内50多种酮的不对称转移氢化和不对称氢化反应,其S/C(底物与催化剂的摩尔比)最高可达5000:1,产物手性芳香醇的光学纯度高达99%ee.     

Understanding the origins of remote asymmetric induction in the boron aldol reactions of beta-alkoxy methyl ketones

We report theoretical studies into the remote 1,5-stereoinduction shown by certain types of beta-alkoxy methyl ketones in boron-mediated aldol reactions with achiral aldehydes. For a range of common alkoxy groups, our calculations are in excellent agreement with experimentally observed diastereoselectivities. In the aldol transition structures, a stabilizing hydrogen bond between the alkoxy oxygen and formyl proton leads to preferential formation of the 1,5-adduct, by minimizing steric interactions between the beta-alkyl group and one of the ligands on boron.