(S)-和(R)-盐酸氟西汀的不对称合成

盐酸氟西汀是一种临床广泛使用的非三环类抗抑郁药, 本工作介绍了一种不对称合成(S)-和(R)-盐酸氟西汀的方法. 以自制的手性噁唑硼烷为催化剂, 将起始原料β-氯苯丙酮不对称催化氢化还原成(S)-或(R)-手性醇, 这一步的化学收率和光学收率都较高. 然后再经两步, (S)-和(R)-手性醇转化为(S)-和(R)-盐酸氟西汀. 整个工艺只需三步, 总收率为66.5%, 盐酸氟西汀对映体的ee值可达98.6%. 还考察了反应温度、溶剂、催化剂的量等因素对β-氯苯丙酮的不对称氢化还原的化学产率和光学收率的影响.     

双手性噁唑硼烷体系催化还原反应的研究

第一次成功设计、合成了新型的双手性噁唑硼烷还原体系，并将其应用于前手性酮的不对称还原。实验结果表明，双手性噁唑硼烷体系在手性相匹配的情况下，对前手性酮还原的对映选择性明显地优于单手性的噁唑硼烷的还原体系。     

由(1R,2S)-麻黄碱制备的硼杂噁唑烷催化甲硼烷不对称还原苯乙酮

由(1R,2S)-麻黄碱制得了五个新的手性硼杂(口恶)唑烷1～5,它们催化甲硼烷不对称还原苯乙酮,获得了高产率的具有38.5～72.4％e.e.的R-1-苯基乙醇。讨论了催化剂的结构-活性关系及反应参数(催化剂用量、反应温度)对还原反应对映选择性的影响。     

Quantum chemical study on enantioselective reduction of aromatic ketones catalyzed by chiral cyclic sulfur‐containing oxazaborolidines. Part 3. Structures of catalyst–alkoxyborane adducts

The chiral cyclic sulfur‐containing oxazaborolidine catalyst reacts with aromatic ketone in the presence of borane to form the catalyst–alkoxyborane adduct with a B‐O‐B‐N four‐membered ring. The ab initio molecular orbital method is employed to study the structures of the catalyst–alkoxyborane adduct. All the calculated systems are optimized completely by means of the Hartree–Fock method at 6‐31g* basis sets. The B‐O‐B‐N four‐membered ring is stable, although there is strong tensile stress in the four‐membered ring. The catalyst–alkoxyborane adduct exists in four stable structures. Among these structures, the largest energy difference is only about 4 kJ/mol. In the catalyst–alkoxyborane adduct, the B(2) N(3) bond in the catalyst is weakened greatly. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 261–268, 2000     

Quantum chemical study on enantioselective reduction of aromatic ketones catalyzed by chiral cyclic sulfur‐containing oxazaborolidines. Part 2. Structures of catalyst–borane–ketone adducts

In the present paper, the ab initio molecular orbital method is employed to study the structures of the adducts of borane and aromatic ketone to chiral cyclic sulfur‐containing oxazaborolidine used as a catalyst in the enantioselective reduction of aromatic ketone. The catalyst–borane–ketone adducts have four different structures. All the structures are optimized completely by means of the Hartree–Fock method at 6‐31g* basis sets. The structure which is of the greatest advantage to a hydride transfer from the borane moiety to the carbonyl carbon of aromatic ketone is the one with the next lowest formation energy, and the plausible transition state for the hydride transfer is predicted to be of a twisted boat structure. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 252–260, 2000     

Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 1. Structures of catalyst–borane–keto oxime ether adducts

In the present work, quantum chemical computations of the enantioselective reduction of keto oxime ether with borane catalyzed by chiral oxazaborolidine are performed by means of the Hartree–Fock and the density functional methods. The structures of oxazaborolidine, oxazaborolidine–borane adduct, and oxazaborolidine–borane–keto oxime ether adducts are optimized completely at the HF/6‐31g* and B3LYP/6‐31g* levels and their properties studied in detail. The oxazaborolidine catalyst is a twisted chair structure and reacts with borane at the nitrogen site of the catalyst to form the catalyst–borane adduct whose formation reaction is exothermic. The catalyst–borane adduct reacts easily with keto oxime ether to form catalyst–borane–keto oxime ether adducts that have eight stable structures. The coordination of the carbonyl oxygen in keto oxime ether at the boron site of the catalyst is of more advantage to the enantioselective reduction of keto oxime ether than the coordination of the oxime nitrogen in the keto oxime ether at the boron site is. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 81: 291–304, 2001     

手性噁唑硼烷结构与还原苯基乙基甲酮的对映选择性研究~≠

本文以苯基乙基甲酮为还原底物,研究了原地(in situ)制备的在3、4、5位具有不同取代基的手性1,3,2-(口恶)唑硼烷催化剂的结构与不对称催化效应关系。研究结果表明,在不对称催化硼烷还原反应中(CBS方法),产物的构型和对映选择性主要受手性(口恶)唑硼烷的4位取代基控制。     

取代基对手性唑噁唑硼烷催化还原苯基乙基酮对映体选择性影响的理论研究

用AM1方法和过渡态理论研究了取代基对含侧链手性噁唑硼烷催化还原苯 基乙杂程逖≡裥缘挠跋欤扑憬峁砻鳎杂逞≡裥匀【鲇?R)和(S)两个对映体? 叫蟹从Φ乃俾食Ｊ龋盋(4)和C(5)位上的取代基呈顺式时，所得对映体以(R) 型为主．对映选择性的高低与噁唑硼烷环上不同位置原子连接的取代基基团的大? ∮泄兀扑憬峁胧笛樽芙岢龅慕崧巯辔呛希? $601 $AThe influence of substituents on the enantioselectivity in asymmetric branched-oxazaborolidine-catalyzed reductions of phenyl- ethyl ketone has been studied by using AMI MO method and transition state theory. The results show that the enantioselectivity is determined by the ratio of the rate constants of two parallel reactions conducting to spatial configurations (R) and (S). When the substituents connecting with C(4) and C(5) are in cis-form the reduction products of phenyl-ethyl ketone in the reactions are mainly of configuration ( R). In asymmetric boron-catalyzed reduction reactions the higher or lower magnitude for enantioselectivity and reaction barrier are governed by various substituents connecting with atoms of oxazaborolidine ring. The computational results are in consistence with experiments.     

吡咯烷并手性噁唑硼烷催化芳香酮的不对称还原机理的量子化学研究

不对称催化还原;吡咯烷并手性噁唑硼烷催化芳香酮的不对称还原机理的量子化学研究