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

The logic of chemical synthesis

简单的原料 复杂的分子

transform

synthesis

反合成分析法retrosynthetic analysis

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 Brownsodium 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)

O

CR R

NaBH4 C

H

RR

OH

H

HH

CH3

B2H6 +H

H

CH

H

CH3

3

B

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 ) 。

(C6H5)3P=CH2 + R2C=O (C6H5)3P=O + R2C=CH2

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 bondbetween 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

CX

Formation of P-ylides

N-ylide( 氮叶立德 )

The semipolar nature of the N-C bondIts 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 ato

m

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. Chem. 89,437 (1977).

R. W. Hoffmann, Dehydrobenzae and Cycloalkynes (Academic Press, New York, 1967).

《有机合成设计》 [ 英 ] S 特纳 化学工业出版社

《叶立德化学》 黄文芳 华中师范大学出版社

《极性转换及其在有机合成中的应用》

刘志昌 科学出版社