《手性合成英》PPT课件.ppt

Elias J. Corey Autobiography,1928 born in Methuen，Massachusetts 1944 entered M.I.T. 参与合成青霉素 1950 completed doctoral work joined University of Illinois 1956 became Professor of Chemistry 1959 work in Harvard,1957年 Elias J. Corey 提出了他的想法：,The Logic of Chemical Synthesis,retrosynthetic analysis 逆合成法,简单的原料,复杂的分子,transform,synthesis,反合成分析法 retrosynthetic analysis,Retrosynthetic tree,树根目标分子,树枝原料,Best Choice?,位置控制,保护基 活化基 桥连因子,To build “left- or right handed“ molecules,Herbert C. Brown,USA Purdue University West Lafayette, IN, USA 1912 -,Georg Wittig,Federal Republic of Germany University of Heidelberg Heidelberg, Germany 1897 - 1987,The Nobel Prize in Chemistry 1979,Laureates: Herbert C. Brown Georg Wittig,“ for their development of the use of boron- and phosphorus-containing compounds, respectively, into important reagents in organic synthesis“,Boron compounds,Herbert C Brown sodium boro-hydride(硼氢化钠) -the reagent of choice for reduction of carbonyl compounds Organoboranes(B2H6) (the most versatile reagents ever created in organic chemistry),can be used for reductions, rearrangements and additions and have opened up a range of new possibilities for linking carbon atoms to each other. 还原 重排 加成,Wittig reaction,organic phosphorus compound with a formal double bond(含双键的有机磷化合物，双键在P和C之间) between phosphorus and carbon react with a carbonyl compound(羰基化合物). The oxygen of the carbonyl compound is exchanged for carbon, the product being an olefin(烯烃)。,这是我们熟悉的Wittig试剂，用于双键化合物的制备,A carbonyl compound(羰基化合物),organic phosphorus compound with a formal double bond between phosphorus and carbon,olefin(烯烃),Fig. 1. Formation of a diradical 被削弱的C-C键,demetalization,有机金属锂化合物,diradical,Formation and characterization of compound 9,zinc dust distillation.,芳基质子作为取代基的不稳定性 惊人发现：umpolung 规则 或极性逆转规则 F 的特异性,Reversal of polarity (umpolung) 极性逆转,Mechanism of formation of o-lithiobiphenyl,Proof of the intermediate occurrence of dehydrobenzene in the reaction of 14 C-labeled chlorobenzene with potassium amide in liquid ammonia,Fig. 8. Proof of the existence of dehydrobenzene through the formation of 10,苯炔中间体存在的证实： 在反应过程中加入二烯体呋喃，分离出产物10,a Diels-Alder addition：,经证实，苯炔中间体存在的时间为：20 milliseconds.,Thermal decomposition reactions used to determine the lifetime of dehydrobenzene in the gas phase,四烷基铵盐上的碳上的氢是否也有不稳定性？,通过： 氯化四甲基铵,甲基锂,五甲基氮,失败！,Formation of Nylides,ylide,Formation of P-ylides,N-ylide(氮叶立德),The semipolar nature of the N-C bond Its ability to add to benzophenone（二苯甲酮）,P-ylide（磷叶立德）,triphenylphosphinemethylene,triphenylphosphineoxide,1，1-diphenylethylene,Fig. 13. Steps in the reaction of triphenylphosphinemethylene with benzophenone,四元环过度态,应用：vitamin A的合成,硼也可以作为 tetracoordinate central atom,参考文献,E.J. Corey, X.-M. Cheng: The Logic of Chemical Synthesis, Wiley Interscience, 1989. E.J. Corey, A.K. Long, S.D. Rubenstein: Computer-Assisted Analysis in Organic Synthesis, Science, Vol 228, 1985, pp 408-418. The Royal Swedish Academy of Sciences, Information about the Nobel Prize in Chemistry 1990 (press release).,Further reading,G. Wittig and M. Rieber, ibid. 562, 187 (1949). G. Wittig and K Clauss, ibid. 577, 26 (1952); ibid. 578,136 (1952). G. Wittig and K. Torssell, Acta Chem. Stand. 7, 1293 (1953). H. Pommer, Angew.