Editing Enantioselective synthesis (section)

===Inception (1815–1905)===
In 1815 the French physicist [[Jean-Baptiste Biot]] showed that certain chemicals could rotate the plane of a beam of polarised light, a property called [[optical activity]].<ref>{{cite book | editor= Lakhtakia, A. | title=Selected Papers on Natural Optical Activity (SPIE Milestone Volume 15) |publisher=SPIE | year=1990}}</ref>
The nature of this property remained a mystery until 1848, when [[Louis Pasteur]] proposed that it had a molecular basis originating from some form of ''dissymmetry'',<ref>{{cite journal|last1=Gal|first1=Joseph|title=Louis Pasteur, language, and molecular chirality. I. Background and Dissymmetry|journal=Chirality|date=January 2011|volume=23|issue=1|pages=1–16|doi=10.1002/chir.20866|pmid=20589938}}</ref><ref>{{cite book | author= Pasteur, L. | title=Researches on the molecular asymmetry of natural organic products, English translation of French original, published by Alembic Club Reprints (Vol. 14, pp. 1–46) in 1905, facsimile reproduction by SPIE in a 1990 book | year=1848}}</ref>
with the term ''chirality'' being coined by [[Lord Kelvin]] a year later.<ref>{{cite journal |title=Tracing the Origins and Evolution of Chirality and Handedness in Chemical Language |author=Pedro Cintas |journal=Angewandte Chemie International Edition |volume=46 |issue=22 |pages=4016–4024 |doi=10.1002/anie.200603714 |year=2007 |pmid=17328087}}</ref>
The origin of chirality itself was finally described in 1874, when [[Jacobus Henricus van 't Hoff|Jacobus Henricus van&nbsp;'t Hoff]] and [[Joseph Le Bel]] independently proposed the [[tetrahedral]] geometry of carbon.<ref>{{cite journal|last1=Le Bel|first1=Joseph|title=Sur les relations qui existent entre les formules atomiques des corps organiques et le pouvoir rotatoire de leurs dissolutions|journal=Bull. Soc. Chim. Fr.|date=1874|volume=22|pages=337–347|url=http://gallica.bnf.fr/ark:/12148/bpt6k2819715/f341.image|trans-title=On the relations which exist between the atomic formulas of organic compounds and the rotatory power of their solutions}}</ref><ref>van 't Hoff, J.H. (1874) [https://babel.hathitrust.org/cgi/pt?id=hvd.32044106337231;view=1up;seq=479 "Sur les formules de structure dans l'espace"] (On structural formulas in space),  ''Archives Néerlandaises des Sciences Exactes et Naturelles'', '''9''' :  445–454.</ref> Structural models prior to this work had been two-dimensional, and van&nbsp;'t Hoff and Le Bel theorized that the arrangement of groups around this tetrahedron could dictate the optical activity of the resulting compound through what became known as the [[Le Bel–van 't Hoff rule]].
[[File:MarckwaldAsymmetricSynthesis.svg|thumb|right|600px|Marckwald's brucine-catalyzed enantioselective decarboxylation of 2-ethyl-2-methyl[[malonic acid]], resulting in a slight excess of the [[levorotary]] form of the 2-methylbutyric acid product.<ref name=Koskinen2012>{{cite book|last1=Koskinen|first1=Ari M.P.|title=Asymmetric synthesis of natural products|date=2013|publisher=Wiley|location=Hoboken, N.J.|isbn=978-1-118-34733-1|pages=17, 28–29|edition=Second}}</ref>]]

In 1894 [[Hermann Emil Fischer]] outlined the concept of [[asymmetric induction]];<ref>{{cite journal|last=Fischer|first=Emil|title=Synthesen in der Zuckergruppe II|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1 October 1894|volume=27|issue=3|pages=3189–3232|doi=10.1002/cber.189402703109|url=https://zenodo.org/record/1425760}}</ref> in which he correctly ascribed selective the formation of <small>D</small>-glucose by plants to be due to the influence of optically active substances within chlorophyll. Fischer also successfully performed what would now be regarded as the first example of enantioselective synthesis, by enantioselectively elongating sugars via a process which would eventually become the [[Kiliani–Fischer synthesis]].<ref>{{cite journal|last=Fischer|first=Emil|author2=Hirschberger, Josef|title=Ueber Mannose. II|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1 January 1889|volume=22|issue=1|pages=365–376|doi=10.1002/cber.18890220183|url=https://zenodo.org/record/1425553}}</ref>
[[Image:Brucine2.svg|thumb|right|200px|Brucine, an [[alkaloid]] [[natural product]] related to [[strychnine]], used successfully as an [[organocatalyst]] by Marckwald in 1904.<ref name=Koskinen2012/>]]

The first enantioselective chemical synthesis is most often attributed to [[Willy Marckwald]], [[Humboldt-Universität zu Berlin|Universität zu Berlin]], for a [[brucine]]-catalyzed enantioselective [[decarboxylation]] of 2-ethyl-2-methyl[[malonic acid]] reported in 1904.<ref name=Koskinen2012/><ref>{{cite journal | doi = 10.1002/cber.19040370165 | title = Ueber asymmetrische Synthese | year = 1904 | author = Marckwald, W. | journal = Berichte der Deutschen Chemischen Gesellschaft | volume = 37 | pages = 349–354| url = https://zenodo.org/record/1426100 }}</ref> A slight excess of the levorotary form of the product of the reaction, 2-methylbutyric acid, was produced; as this product is also a [[natural product]]—e.g., as a side chain of [[lovastatin]] formed by its diketide synthase (LovF) during its [[biosynthesis]]<ref>{{cite journal|last1=Campbell|first1=Chantel D.|last2=Vederas|first2=John C.|title=Biosynthesis of lovastatin and related metabolites formed by fungal iterative PKS enzymes|journal=Biopolymers|date=23 June 2010|volume=93|issue=9|pages=755–763|doi=10.1002/bip.21428|pmid=20577995|doi-access=free}}</ref>—this result constitutes the first recorded total synthesis with enantioselectivity, as well other firsts (as Koskinen notes, first "example of [[asymmetric catalysis]], [[enantioselectivity|enantiotopic selection]], and [[organocatalysis]]").<ref name=Koskinen2012/> This observation is also of historical significance, as at the time enantioselective synthesis could only be understood in terms of [[vitalism]]. At the time many prominent chemists such as [[Jöns Jacob Berzelius]] argued that natural and artificial compounds were fundamentally different and that chirality was simply a manifestation of the 'vital force' which could only exist in natural compounds.<ref>{{citation | editor-last = Cornish-Bawden | editor-first= Athel | title = New Beer in an Old Bottle. Eduard Buchner and the Growth of Biochemical Knowledge | publisher = Universitat de València | year = 1997 | pages = 72–73 | url = https://books.google.com/books?id=HFrBP8S7my4C&q=Berzelius+vitalism+1815&pg=PA73| isbn= 978-84-370-3328-0}}</ref> Unlike Fischer, Marckwald had performed an enantioselective reaction upon an achiral, ''un-natural'' starting material, albeit with a chiral organocatalyst (as we now understand this chemistry).<ref name=Koskinen2012/><ref>Much of this early work was published in German, however contemporary English accounts can be found in the papers of [[Alexander McKenzie (chemist)|Alexander McKenzie]], with continuing analysis and commentary in modern reviews such as Koskinen (2012).</ref><ref>{{cite journal|last=McKenzie|first=Alexander|title=CXXVII.Studies in asymmetric synthesis. I. Reduction of menthyl benzoylformate. II. Action of magnesium alkyl haloids on menthyl benzoylformate|journal=J. Chem. Soc. Trans.|date=1 January 1904|volume=85|pages=1249–1262|doi=10.1039/CT9048501249|url=https://zenodo.org/record/1567059}}</ref>