Editing Enantioselective synthesis (section)

===Modern age (since 1965)===
The Cahn–Ingold–Prelog priority rules (often abbreviated as the [[CIP system]]) were first published in 1966; allowing enantiomers to be more easily and accurately described.<ref>{{Cite journal |author1= Robert Sidney Cahn |author2-link=Christopher Kelk Ingold |author2=Christopher Kelk Ingold |author3-link=Vladimir Prelog |author3=Vladimir Prelog | title = Specification of Molecular Chirality | journal = [[Angewandte Chemie International Edition]] | volume = 5 | issue = 4 | pages = 385–415 | year = 1966 | doi = 10.1002/anie.196603851|author1-link=Robert Sidney Cahn }}</ref><ref>{{cite journal |author1= Vladimir Prelog |author2=Günter Helmchen  | title = Basic Principles of the CIP-System and Proposals for a Revision | journal = [[Angewandte Chemie International Edition]] | volume = 21 | issue = 8 | pages = 567–583 | year = 1982 | doi = 10.1002/anie.198205671|author1-link=Vladimir Prelog }}</ref>
The same year saw first successful enantiomeric separation by [[gas chromatography]]<ref>{{cite journal|last=Gil-Av|first=Emanuel|author2=Feibush, Binyamin |author3=Charles-Sigler, Rosita |title=Separation of enantiomers by gas liquid chromatography with an optically active stationary phase|journal=Tetrahedron Letters|year=1966|volume=7|issue=10|pages=1009–1015|doi=10.1016/S0040-4039(00)70231-0}}</ref> an important development as the technology was in common use at the time.

Metal-catalysed enantioselective synthesis was pioneered by [[William S. Knowles]], [[Ryōji Noyori]] and [[K. Barry Sharpless]]; for which they would receive the 2001 [[Nobel Prize in Chemistry]]. Knowles and Noyori began with the development of [[asymmetric hydrogenation]], which they developed independently in 1968. Knowles replaced the achiral [[triphenylphosphine]] ligands in [[Wilkinson's catalyst]] with chiral [[phosphine ligand]]s. This experimental catalyst was employed in an asymmetric hydrogenation with a modest 15% [[enantiomeric excess]]. Knowles was also the first to apply enantioselective metal catalysis to industrial-scale synthesis; while working for the [[Monsanto Company]] he developed an enantioselective hydrogenation step for the production of [[L-DOPA]], utilising the [[DIPAMP]] ligand.<ref>{{cite journal|last=Vineyard|first=B. D.|author2=Knowles, W. S. |author3=Sabacky, M. J. |author4=Bachman, G. L. |author5= Weinkauff, D. J. |title=Asymmetric hydrogenation. Rhodium chiral bisphosphine catalyst|journal=Journal of the American Chemical Society|year=1977|volume=99|issue=18|pages=5946–5952|doi=10.1021/ja00460a018|bibcode=1977JAChS..99.5946V }}</ref><ref>{{cite journal|last=Knowles|first=William S.|title=Asymmetric Hydrogenations (Nobel Lecture) |journal=Angewandte Chemie International Edition|year=2002|volume=41|issue=12|pages=1999–2007|doi=10.1002/1521-3773(20020617)41:12<1998::AID-ANIE1998>3.0.CO;2-8|pmid=19746594}}</ref><ref>{{cite journal|last1=Knowles|first1=W. S.|title=Application of organometallic catalysis to the commercial production of L-DOPA|journal=Journal of Chemical Education|date=March 1986|volume=63|issue=3|pages=222|doi=10.1021/ed063p222|bibcode=1986JChEd..63..222K}}</ref>

{| align="center"
|- 
|[[File:Hydrogenation-Knowles1968.png|350px]]
|width="100px"|
|[[File:AsymmetricSynthesisNoyori.png|350px]]
|-
!align="center"|Knowles: Asymmetric hydrogenation (1968)
|width="100px"|
!align="center"|Noyori: Enantioselective cyclopropanation (1968)
|}

Noyori devised a copper complex using a chiral [[Schiff base]] ligand, which he used for the [[Intermolecular metal-catalyzed carbenoid cyclopropanations|metal–carbenoid cyclopropanation]] of [[styrene]].<ref>{{cite journal | title = Homogeneous catalysis in the decomposition of diazo compounds by copper chelates: Asymmetric carbenoid reactions | journal = [[Tetrahedron (journal)|Tetrahedron]] | volume = 24 | issue = 9 | year = 1968 | pages = 3655–3669 |author1=H. Nozaki |author2=H. Takaya |author3=S. Moriuti |author4=R. Noyori | doi = 10.1016/S0040-4020(01)91998-2}}</ref>  
In common with Knowles' findings, Noyori's results for the enantiomeric excess for this first-generation ligand were disappointingly low: 6%. However continued research eventually led to the development of the [[Noyori asymmetric hydrogenation]] reaction.

[[File:Sharpless Oxyamination Scheme.png|thumb|left|250px|The Sharpless oxyamination]]
Sharpless complemented these reduction reactions by developing a range of asymmetric oxidations ([[Sharpless epoxidation]],<ref>{{cite journal|last=Katsuki|first=Tsutomu|author2=Sharpless, K. Barry|title=The first practical method for asymmetric epoxidation|journal=Journal of the American Chemical Society|year=1980|volume=102|issue=18|pages=5974–5976|doi=10.1021/ja00538a077|bibcode=1980JAChS.102.5974K }}</ref> [[Sharpless asymmetric dihydroxylation]],<ref>{{cite journal|last=Jacobsen|first=Eric N.|author2=Marko, Istvan. |author3=Mungall, William S. |author4=Schroeder, Georg. |author5= Sharpless, K. Barry. |title=Asymmetric dihydroxylation via ligand-accelerated catalysis|journal=Journal of the American Chemical Society|year=1988|volume=110|issue=6|pages=1968–1970|doi=10.1021/ja00214a053|bibcode=1988JAChS.110.1968J }}</ref> [[Sharpless oxyamination]]<ref>{{cite journal|last=Sharpless|first=K. Barry|author2=Patrick, Donald W. |author3=Truesdale, Larry K. |author4= Biller, Scott A. |title=New reaction. Stereospecific vicinal oxyamination of olefins by alkyl imido osmium compounds|journal=Journal of the American Chemical Society|year=1975|volume=97|issue=8|pages=2305–2307|doi=10.1021/ja00841a071|bibcode=1975JAChS..97.2305S }}</ref>) during the 1970s and 1980s. With the asymmetric oxyamination reaction, using [[osmium tetroxide]], being the earliest.

During the same period, methods were developed to allow the analysis of chiral compounds by [[NMR]]; either using chiral derivatizing agents, such as [[Mosher's acid]],<ref>{{cite journal | author = J. A. Dale, D. L. Dull and [[Harry S. Mosher|H. S. Mosher]] | title =α-Methoxy-α-trifluoromethylphenylacetic acid, a versatile reagent for the determination of enantiomeric composition of alcohols and amines | year = 1969 | journal = [[J. Org. Chem.]] | volume = 34 | issue = 9 | pages = 2543–2549 | doi = 10.1021/jo01261a013}}</ref>
or [[europium]] based shift reagents, of which Eu(DPM)<sub>3</sub> was the earliest.<ref>{{cite journal|last=Hinckley|first=Conrad C.|title=Paramagnetic shifts in solutions of cholesterol and the dipyridine adduct of trisdipivalomethanatoeuropium(III). A shift reagent|journal=Journal of the American Chemical Society|year=1969|volume=91|issue=18|pages=5160–5162|doi=10.1021/ja01046a038|pmid=5798101|bibcode=1969JAChS..91.5160H }}</ref>

Chiral auxiliaries were introduced by [[E.J. Corey]] in 1978<ref>{{cite journal|last=Ensley|first=Harry E.|author2=Parnell, Carol A. |author3=Corey, Elias J. |title=Convenient synthesis of a highly efficient and recyclable chiral director for asymmetric induction|journal=The Journal of Organic Chemistry|year=1978|volume=43|issue=8|pages=1610–1612|doi=10.1021/jo00402a037}}</ref> and featured prominently in the work of [[Dieter Enders]]. Around the same time enantioselective organocatalysis was developed, with pioneering work including the [[Hajos–Parrish–Eder–Sauer–Wiechert reaction]].
Enzyme-catalyzed enantioselective reactions became more and more common during the 1980s,<ref>{{cite journal|last=Sariaslani|first=F.Sima|author2=Rosazza, John P.N.|title=Biocatalysis in natural products chemistry|journal=Enzyme and Microbial Technology|year=1984|volume=6|issue=6|pages=242–253|doi=10.1016/0141-0229(84)90125-X}}</ref> particularly in industry,<ref>{{cite journal|last=Wandrey|first=Christian|author2=Liese, Andreas |author3=Kihumbu, David |title=Industrial Biocatalysis: Past, Present, and Future|journal=Organic Process Research & Development|year=2000|volume=4|issue=4|pages=286–290|doi=10.1021/op990101l}}</ref> with their applications including [[asymmetric ester hydrolysis with pig-liver esterase]]. The emerging technology of [[genetic engineering]] has allowed the tailoring of enzymes to specific processes, permitting an increased range of selective transformations. For example, in the asymmetric hydrogenation of [[statin]] precursors.<ref name="statin" />