10.1002/anie.199013201
Crossref journal-article
Wiley
Angewandte Chemie International Edition in English (311)
Abstract

AbstractThis review article is an attempt to sketch the important developments in organic synthesis during the past 25 years, and to project them into the future.—The primary motivations that once induced chemists to undertake natural product syntheses no longer exist. Instead of target structures themselves, molecular function and activity now occupy center stage. Thus, inhibitors with an affinity for all the important natural enzymes and receptors have moved to the fore as potential synthetic targets.—New syntheticmethodsare most likely to be encountered in the fields of biological and organometallic chemistry. Enzymes, whole organisms, and cell cultures for enan‐tioselective synthesis of specific substances have already been incorporated into the synthetic arsenals of both research laboratories and industry. In addition, designing appropriate analogues to transition states and intermediates should soon make it possible, with the aid of the mammalian immune system and gene technology, to prepare catalytically active monoclonal antibodies for almost any reaction; perhaps, more important, such processes will increasingly come to be applied on an industrial scale.‐The discovery of truly new reactions is likely to be limited to the realm of transition‐metal organic chemistry, which will almost certainly provide us with additional “miracle reagents” in the years to come. As regards main group elements (“organoelemental chemistry”), we can surely anticipate further stepwise improvements in experimental procedures and the broader application of special techniques, leading to undreamed of efficiency and selectivity with respect to known procedures. The primary center of attention for all synthetic methods will continue to shift toward catalytic and enantioselective variants; indeed, it will not be long before such modifications will be available with every standard reaction for converting achiral educts into chiral products. Analysis, spectroscopy, structure determination, theory, and electronic data processing have all become indispensable in organic synthesis. Only with the aid of these “tools” will the methods of organic chemistry permit selective syntheses of ever larger and more complex systems on both the molecular and supramolecular levels.—Examples have been introduced throughout this discourse to illustrate its many themes, and a very comprehensive bibliography should help the interested reader become more familiar with important keywords and authors.[The list of references is also available upon request in the form of a Microsoft Word© file on diskette.]—This article will have served its intended purpose if it changes the minds of some of those who claim organic chemistry is amature science, and if it causes students to discover the vitality and forcefulness with which organic synthesis is meeting new challenges and attempting to fulfill old dreams.Er zeigt uns so in seinem wissenschaftlichen Leben, daß die Chemie nicht von einer Theorie, nicht von einer Methode aus zu erschöpfen ist, und daß Erkenntnis und Nutzen in ihr untrennbar verwoben sind.“He showed us through his scientific life that chemistry cannot be exploited fully with the aid of asingletheory or asinglemethodology, and that it is a field in which knowledge and application are inextricably linked.” G. Bugge:Das Buch der großen Chemiker, Vol. 2, 4th reprint, Verlag Chemie, Weinheim 1974.R. Koch, writing about Louis Pasteur

Bibliography

Seebach, D. (1990). Organic Synthesis—Where now? Angewandte Chemie International Edition in English, 29(11), 1320–1367. Portico.

Authors 1
  1. Dieter Seebach (first)
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  239. there were two symposia on organofluorine compounds with the titles "Symposium on Modern Synthetic Methods in Fluorine Chemistry" and "Symposium on Biologically Active Organofluorine Compounds" (The 1989 International Chemical Congress of Pacific Basin Societies Book of Abstracts II). The following fluorine symposia were arranged in the course of 1990 ACS conventions: 199th National ACS Meeting 22-27 April 1990 Boston MA: Symposium on the Effects of Selective Fluorination on Reactivity Symposium on Fluorine Containing Polymeric Materials
  240. 200th National ACS Meeting 21-31 Aug. 1990. Washington. D.C.: Symposium on Mass Spectrometry of Fluorinated Compounds Symposium on Fluorine Chemistry for Organic Chemists.
  241. The growing interest in fluorine chemistry is documented by the steadily increasing number of publications in the area. The following diagram was constructed on the basis of publications covered byChemical Abstractsin the period from Jan. 1967 to March 1990 (solid bars: total number in units of 100; dotted bars: publications indexed under “fluorine”; black line: contribution of “fluorine” publications in terms of percent).
  242. {'key': 'e_1_2_1_91_2', 'volume-title': 'Chemistry of Organic Fluorine Compounds', 'author': 'Hudlicky M.', 'year': '1976'} / Chemistry of Organic Fluorine Compounds by Hudlicky M. (1976)
  243. {'key': 'e_1_2_1_91_3', 'volume-title': 'Fluorine in Organic Chemistry', 'author': 'Chambers R. D.', 'year': '1973'} / Fluorine in Organic Chemistry by Chambers R. D. (1973)
  244. {'key': 'e_1_2_1_91_4', 'first-page': '141', 'volume-title': 'Molecular Structure and Energetics', 'author': 'Smart B. E.', 'year': '1986'} / Molecular Structure and Energetics by Smart B. E. (1986)
  245. {'key': 'e_1_2_1_91_5', 'volume-title': 'Fluorine‐Containing Molecules—Structure, Reactivity, Synthesis and Applications', 'author': 'Liebman J. F.', 'year': '1988'} / Fluorine‐Containing Molecules—Structure, Reactivity, Synthesis and Applications by Liebman J. F. (1988)
  246. {'key': 'e_1_2_1_91_6', 'volume-title': 'Fluorine in Bioorganic Chemistry', 'author': 'Welch J. T.', 'year': '1990'} / Fluorine in Bioorganic Chemistry by Welch J. T. (1990)
  247. {'key': 'e_1_2_1_92_2', 'first-page': '134', 'volume': '39', 'author': 'Haas A.', 'year': '1985', 'journal-title': 'Chimia'} / Chimia by Haas A. (1985)
  248. {'key': 'e_1_2_1_92_3', 'first-page': '305', 'volume': '39', 'author': 'Vyplel H.', 'year': '1985', 'journal-title': 'Chimia'} / Chimia by Vyplel H. (1985)
  249. 10.1002/0471264180.or035.03 / Org. React. (N. Y.) by Hudlicky M. (1988)
  250. 10.1016/S0022-1139(00)85279-3
  251. 10.5059/yukigoseikyokaishi.47.27
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  253. 10.2533/chimia.1990.120 / Chimia by Aucr K. (1990)
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  255. 10.5059/yukigoseikyokaishi.45.664
  256. (j) “New Catalytic Reactions of the Hydrolytic Enzymes in Fluorine Chemistry”:T.Kilazume T.Yamazaki 45(1987)888–897; (10.5059/yukigoseikyokaishi.45.888)
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  258. {'key': 'e_1_2_1_92_13', 'first-page': '97', 'volume': '10', 'author': 'Imperiali B.', 'year': '1988', 'journal-title': 'Adv. Biotechnol. Processes'} / Adv. Biotechnol. Processes by Imperiali B. (1988)
  259. As an outsider one has the impression that specialists take it for granted that reactions of “normal” compoundswon'twork with fluorine derivatives; if they do succeed the astonishing news warrants immediate publication! A few personal experiences would suggest that one should be prepared for anything with even the simplest reactions—a thrilling prospect; see [94–97] (cf. also Chapter 4. “Aliphatic Fluoronitro Com‐pounds” in [105a]).
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  762. I wish to thank ProfessorEdwin Vedejsfor providing me with a manuscript copy.
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  944. For applications of the Suzuki coupling see [341e].
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  958. see also: “Recent Developments in Organocopper Chemistry”. Tetrahedron Symposia‐in‐Print Number 35:
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  966. (d) for the use of silylcuprates in the Michael addition of Si‐groups see [293 294];
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  1001. G.Bold R.Duthaler P.Herold W.Lottenbach K.Oertle M.Riediker G.Rihs A.Togni Lectures at theHerbstversammlung der Schweizerischen Chemischen Gesellschaft Bern. October 1989 Abstract Volume pp. 20 21 22. (10.1002/chin.198930105)
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  1017. I wish to thank ProfessorRyoji Noyorimost sincerely for providing me with manuscript copies prior to their publication [432 433] as well as for the chromatogram in Fig. 13 and permission to include these findings here.
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  1019. We suggested [352] in 1980 use of the abbreviation “EPC synthesis” as a generic term for the preparation of enantiomericallypurecompounds. While there might be disagreement over the definition of “purity” (which is dependent above all on the sensitivity of the analytical methods employed) the terminology is otherwise unambiguous. Expressions like “homochiral compounds” [437] or “isochiral compounds” [438] are unfortunate in several respects. Thus “homochiral” has long been used in comparing the chirality oftwosimilar compounds or a pair of chiral molecules in the unit cell of a crystal but it is now considered appropriate for describing a flask full of (+ )‐tartaric acid (1023molecules per mole)! Expressions like “chiral synthesis” and “racemic synthesis” have also become common; while these may be permissible in English (which also tolerates combinations like “married name” and “fishing pond”) they certainly cannot be translated directly into German. The equally correct expression “chiral not racemic” is more awkward than “enantiomerically pure”. Finally let me urge that the matter not be carried too far; in most cases all that is required is judicious use ofRorS!
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  1022. Isochiral:Under discussion with respect to the preparation of a new edition of the classic textbook of stereochemistry byE. L.Eliel
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  1027. “Industrial Application of Asymmetric Synthesis” is the announced theme of the following conference:2nd Int. IUPAC Symp. Org. Chem. Technological Perspectives(Baden‐Baden April 1991).
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  1033. “Chiralily Recognition in Synthesis” (Fine Chemicals Group Society of Chemical Industry. London 1988). “Synthesis from Natural Homochiral Precursors” (Fine Chemicals Group Society of Chemical Industry. London 1990). “Second International Symposium on Chiral Discrimination” (Rome 1991).
  1034. Chemistry in Britain. 1989
  1035. As if there were not already enough periodicals‐and it were not already possible to present every good piece of work on the subject in one of the standard national or international chemical journals!
  1036. Twenty years ago everything known about stereoselective reactions could be presented together in the single book byJ. D.MorrisonandH. S.Mosher:Asymmetric Organic Reactions Prentice Hall 1971 (ca. 450 pp.).
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  1087. “Synthesis of Chiral Non‐Racemic Compounds” Tetrahedron Symposia‐in‐Print Number 15:
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  1100. {'issue': '11', 'key': 'e_1_2_1_483_3', 'first-page': '88', 'volume': '1981', 'journal-title': 'Spektrum Wiss.'} / Spektrum Wiss.
  1101. 10.1126/science.221.4608.351
  1102. Even a general‐circulation newspaper like DIE ZEIT (R. Schwerthöffer Die ZeitNo. 10 2 March 1990 p. 96) recently devoted a half page in its science section to the subjectThe Art of Catalysis(“Die Chemie nutzt natürliche Vorbilder”) mentioning among other thingsCorey's“Chemzymes”.
  1103. Previously cited books and reviews covering biological‐chemical synthetic methods [79 114 125 126 241 354] A few additional more recent articles: (a) “Enzymes in Organic Syntheses”: J. B. Jones in F. E. C. S. Int. Conf. Chem. Biotechnol. Biol. Act. Nat. Prod. (3.) VCH Verlagsgesellschaft Weinheim 1987 pp. 18–39;
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  1110. {'key': 'e_1_2_1_487_2', 'first-page': '545', 'volume': '2', 'author': 'Levene P. A.', 'year': '1943', 'journal-title': 'Coll.'} / Coll. by Levene P. A. (1943)
  1111. {'key': 'e_1_2_1_487_3', 'first-page': '428', 'volume': '3', 'author': 'Helferich B.', 'year': '1955', 'journal-title': 'Coll.'} / Coll. by Helferich B. (1955)
  1112. {'key': 'e_1_2_1_487_4', 'first-page': '1', 'volume': '63', 'author': 'Seebach D.', 'year': '1985', 'journal-title': 'Coll.'} / Coll. by Seebach D. (1985)
  1113. {'key': 'e_1_2_1_487_5', 'first-page': '10', 'volume': '63', 'author': 'Jones J. B.', 'year': '1985', 'journal-title': 'Coll.'} / Coll. by Jones J. B. (1985)
  1114. {'key': 'e_1_2_1_487_6', 'first-page': '56', 'volume': '68', 'author': 'Mori K.', 'year': '1989', 'journal-title': 'Coll.'} / Coll. by Mori K. (1989)
  1115. {'key': 'e_1_2_1_487_7', 'first-page': '19', 'volume': '69', 'author': 'Eberle M.', 'year': '1990', 'journal-title': 'Coll.'} / Coll. by Eberle M. (1990)
  1116. {'key': 'e_1_2_1_488_2', 'first-page': '269', 'volume': '2', 'author': 'Fischli A.', 'year': '1980', 'journal-title': 'Mod. Synth. Method'} / Mod. Synth. Method by Fischli A. (1980)
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  1118. {'key': 'e_1_2_1_489_2', 'volume-title': 'Biotransformations in Preparative Organic Chemistry (The Use of Isolated Enzymes end Whole Cell Systems in Synthesis)', 'author': 'Davies H. G.', 'year': '1989'} / Biotransformations in Preparative Organic Chemistry (The Use of Isolated Enzymes end Whole Cell Systems in Synthesis) by Davies H. G. (1989)
  1119. Previously cited books and reviews on the topic of organometallic catalysis (263b 388 390 394 400 402 405–407 433 435) above all the articles byJ. K.Stille L. S.HegedusandR.Scheffoldin [389] and citations in Scheme 17.
  1120. {'key': 'e_1_2_1_490_3', 'first-page': '654', 'volume': '1988', 'author': 'Brunner H.', 'journal-title': 'Synthesis'} / Synthesis by Brunner H.
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  1125. {'key': 'e_1_2_1_491_2', 'volume-title': 'Catalysis of Organic Reactions', 'author': 'Blackburn D. W.', 'year': '1990'} / Catalysis of Organic Reactions by Blackburn D. W. (1990)
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  1127. In other words biotechnology really is just an “old hat with new feathers” (H. Metz inMerck‐Spektrum.Switzerland No. 2. 1987).
  1128. For example shikonin from the firm Mitsui Petrochemical Industries. Ltd. Iwakuni Yamaguchi‐ken 740 (Japan).
  1129. {'key': 'e_1_2_1_495_2', 'first-page': '1001', 'volume': '25', 'author': 'DiCosmo F.', 'year': '1989', 'journal-title': 'Chem. Br.'} / Chem. Br. by DiCosmo F. (1989)
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  1132. {'key': 'e_1_2_1_497_3', 'volume-title': 'Microbial transformations on non‐steroid cyclic compounds', 'author': 'Kieslich K.', 'year': '1976'} / Microbial transformations on non‐steroid cyclic compounds by Kieslich K. (1976)
  1133. Only papers of interest to the synthetic chemist have been considered [488b].
  1134. 10.1002/hlca.19830660209
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  1137. One need only consider the many possible conditions for an aldol addition (see [331] and Scheme 26) or for reduction with a complex hydride M1(M2H4‐nXn)b. in which M1= Li Na K Zn Bu4N M2= B Al X = RO RCOO R2N with n = 1–3 (there are entire books on the subject!).
  1138. 10.1021/ja00356a041
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  1140. {'key': 'e_1_2_1_504_2', 'first-page': '172', 'volume': '40', 'author': 'Ehrler J.', 'year': '1986', 'journal-title': 'Chimia'} / Chimia by Ehrler J. (1986)
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  1142. For extensive competent discussions of the subject containing numerous literature citations see [486b e; 488b].
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  1148. Cubes of concentrated cell masses of the anaerobic microorganismThermoanaerobium brockiican be kept wrapped in aluminum foil in a freezer—like baker's yeast in a refrigerator—for long periods of time without loss of reductase activity [506b].
  1149. Proteinogenic amino acids are produced in Japan either by fermentative techniques or by the enantioselective cleavage of amino acid derivatives with immobilized microorganisms or peptidase enzymes: “Production of Optically Active Amino Acids Using Immobilized Biocalalysts”:T.Tosa Int. Chem. Congr. Pacific Basin Societies 17–22 Dec. 1989 Honolulu HI. Abstr. ORGN 615.
  1150. Degussa utilizes membrane techniques [233] cf. also [511]. Nevertheless much of the Degussa amino acid output is derived from protein hydrolyzates (animal skin hair horn hoof or feathers or protein‐containing material from plants) [233].
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  1166. Another case I would prefer to regard as a “youthful sin” (cf. Scheme 24b) is my suggestion [352]–taken up by many others as well–that this process be designated the “mesotrick”. Such expressions really should be confined to the—important! —realm of laboratory jargon.
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  1187. …. or might one here employ the adjectivepromiscuous?Cf. the classical picture of the “key and keyhole”.
  1188. 10.1021/ja00538a077
  1189. 10.1021/ja00410a053
  1190. {'key': 'e_1_2_1_537_4', 'first-page': '194', 'volume-title': 'Asymmetric Synthesis', 'author': 'Rossiter B. E.', 'year': '1985'} / Asymmetric Synthesis by Rossiter B. E. (1985)
  1191. “Asymmetric Epoxidation of Allylic Alcohols: The Sharpless Epoxidation”;
  1192. 10.1055/s-1986-31489
  1193. 10.1002/nadc.19890371210
  1194. 10.1021/jo00360a058
  1195. 10.1021/ja00230a045
  1196. 10.1021/jo00293a001
  1197. This has been designated us “reagent control” [437]—in contrast to “substrate control”. In German it would have to be expressed as “durch das Reagens gesteuert”. I well remember the sermons on a similar theme by my thesis advisorRudolf Criegee who was at that time editor of “Chemische Berichte:es muß heißen kinetisch oder thermodynamichgesteuerte.nicht kontrollierte Reaktion; Kontrolle hat im Deutschen cine vom Englischen ‘control’ verschiedene Bedeutung!” From the fact that the term “stereocontrol” is about to replace “stereoselectivity” we must conclude that now everything is “under control”.
  1198. “Asymmetric Synthesis using Organometallic Catalysts”:H. B.Kaganin [388] Vol. 8 chap. 53. pp. 463–498 and the original literature cited therein.
  1199. 10.1016/B978-0-08-092493-9.50011-6
  1200. 10.1002/ange.19870990304
  1201. 10.1002/anie.198701901
  1202. 10.1021/cr00098a001
  1203. 10.1021/ja00188a089
  1204. 10.1021/jo00230a017
  1205. 10.1021/ja00365a030
  1206. 10.1021/jo00211a039
  1207. 10.1016/S0040-4039(00)98780-X
  1208. 10.1021/ja00214a053
  1209. 10.1021/ja00280a056
  1210. 10.1016/S0040-4039(00)82336-9
  1211. 10.1021/ja00196a045
  1212. {'key': 'e_1_2_1_547_2', 'first-page': '1', 'volume-title': 'Organic Synthesis‐Theory and Applications, A Research Annual', 'author': 'Taschner M. J.', 'year': '1989'} / Organic Synthesis‐Theory and Applications, A Research Annual by Taschner M. J. (1989)
  1213. 10.1002/nadc.19870350307
  1214. see also the article byHelmchenet al. [462]:
  1215. 10.1021/jo00268a001
  1216. 10.1021/ja00187a093
  1217. One should also note that it has become common to speak of Lewis acid‐catalyzed reactions even when equimolar amounts or even lame excesses of SnCl4. TiX4. or BF3—ether are added in which case the Lewis acid could be regarded as part of the solvent!
  1218. 10.1016/B978-0-08-092493-9.50007-4
  1219. See for example the semicorrin ligand proposed for transition‐metal‐catalyzed reactions byA. Pfaltz[490e] as well as B and C in Scheme 32.
  1220. 10.1021/ja00279a083
  1221. 10.1016/S0040-4039(00)96695-4
  1222. 10.1021/jo00290a002
  1223. 10.1016/S0040-4039(00)99546-7
  1224. 10.1021/ja00248a045
  1225. {'key': 'e_1_2_1_553_3', 'first-page': '1302', 'volume': '1987', 'author': 'Yamada J.', 'journal-title': 'J. Chem. Soc. Chem. Commun.'} / J. Chem. Soc. Chem. Commun. by Yamada J.
  1226. 10.5059/yukigoseikyokaishi.45.101
  1227. With few exceptions lithium also docs not exceed the limit of four tetrahedrally oriented ligands; sec (172) and references cited therein. Higher coordination numbers with this element appear to result largely from ionic interactions.
  1228. Mean lengths for the bonds [Å] between N C and O and a number of the metals that are important in synthetic applications.Commentary: The average bond length for pure B/C/N/O‐compounds are taken from [102a]. Average bond lengths for Ti and Zn compounds are derived from [102h] and apply to compounds containing a metal bonded to a methyl group or complexes with aliphatic amines or aliphatic ethers. In the case of the Ti‐CH3 group only two widely divergent values have been reported (1.969 and 2.206 Å). The rest of the data resulted from a search in the CSD [189] for comparable bonds (only trimethyl compounds in the case of Al‐C and Sn‐C). If more than twenty values were found the average has been supplemented (in parentheses) with the standard deviation applicable to the last reported digit. Since the reported values were obtained on the basis of differing criteria they should be regarded only as points of reference.
  1229. 10.1021/ja00187a061
  1230. {'key': 'e_1_2_1_557_3', 'first-page': '49', 'volume-title': 'Stere‐ochemistry of Organic and Bioorganic Transformations, Workshop Conferences Hoechst', 'author': 'Masamune S.', 'year': '1987'} / Stere‐ochemistry of Organic and Bioorganic Transformations, Workshop Conferences Hoechst by Masamune S. (1987)
  1231. E. J.Corey Proc. 31st Natl. Org. Symp. Am. Chem. Soc.June 1989 pp. 1–14
  1232. 10.1021/ja00252a056
  1233. 10.1021/ja00259a075
  1234. 10.1016/S0040-4039(01)93796-7
  1235. 10.1016/S0040-4039(00)94578-7
  1236. 10.1021/jo00247a044
  1237. 10.1016/S0040-4039(00)94581-7
  1238. 10.1016/S0040-4039(00)82359-X
  1239. 10.1021/ja00219a059
  1240. 10.1016/0040-4039(88)85121-9
  1241. 10.1016/S0040-4039(01)93871-7
  1242. 10.1002/hlca.19770600202
  1243. The prophetic observations ofWoodwardin his famous 1956 essay on the subject of “Synthesis” [39] remain just as valid today. On the other hand it was left to a magician like Stork to propose a time scale: “So it is not surprising that organic synthesis is far from the level that many people assume. Progress is continuing hut there will not be any dramatic developments. It is more like a glacier that gradually moves forward until it has finally covered an entire region but it will still becenturiesbefore synthesis has acquired the status that many people already ascribe to it today” [44].
Dates
Type When
Created 21 years, 8 months ago (Dec. 31, 2003, 4:03 a.m.)
Deposited 1 year, 7 months ago (Jan. 11, 2024, 3:23 p.m.)
Indexed 2 days, 16 hours ago (Sept. 3, 2025, 5:50 a.m.)
Issued 34 years, 10 months ago (Nov. 1, 1990)
Published 34 years, 10 months ago (Nov. 1, 1990)
Published Online 21 years, 8 months ago (Dec. 22, 2003)
Published Print 34 years, 10 months ago (Nov. 1, 1990)
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@article{Seebach_1990, title={Organic Synthesis—Where now?}, volume={29}, ISSN={0570-0833}, url={http://dx.doi.org/10.1002/anie.199013201}, DOI={10.1002/anie.199013201}, number={11}, journal={Angewandte Chemie International Edition in English}, publisher={Wiley}, author={Seebach, Dieter}, year={1990}, month=nov, pages={1320–1367} }