Editing Enantioselective synthesis (section)

==Overview==
[[File:Energy diagram for enantioselective synthesis.png|300px|thumb|An [[Energy profile (chemistry)|energy profile]] of an enantioselective addition reaction.]]

Many of the building blocks of biological systems such as [[sugar]]s and [[amino acid]]s are produced exclusively as one [[enantiomer]]. As a result, living systems possess a high degree of [[Chirality (chemistry)|chemical chirality]] and will often react differently with the various enantiomers of a given compound. Examples of this selectivity include:
* '''Flavour:''' the [[artificial sweetener]] [[aspartame]] has two enantiomers. <small>L</small>-aspartame tastes sweet whereas <small>D</small>-aspartame is tasteless.<ref>{{cite journal|last=Gal|first=Joseph|title=The Discovery of Stereoselectivity at Biological Receptors: Arnaldo Piutti and the Taste of the Asparagine Enantiomers-History and Analysis on the 125th Anniversary|journal=Chirality|year=2012|volume=24|issue=12|pages=959–976|doi=10.1002/chir.22071|pmid=23034823}}</ref>
* '''Odor:''' ''R''-(–)-[[carvone]] smells like [[spearmint]] whereas ''S''-(+)-carvone smells like [[caraway]].<ref>{{cite journal | doi = 10.1021/jf60176a035 | title=Chemical and sensory data supporting the difference between the odors of the enantiomeric carvones |author1=Theodore J. Leitereg |author2=Dante G. Guadagni |author3=Jean Harris |author4=Thomas R. Mon |author5=Roy Teranishi | journal=[[J. Agric. Food Chem.]] | volume=19 | issue=4 | year=1971 | pages=785–787| bibcode=1971JAFC...19..785L }}</ref>
* '''Drug effectiveness:''' the [[antidepressant]] drug [[Citalopram]] is sold as a [[racemic]] mixture. However, studies have shown that only [[Escitalopram|the (''S'')-(+) enantiomer]] is responsible for the drug's beneficial effects.<ref name="pmid15107657">{{cite journal |vauthors=Lepola U, Wade A, Andersen HF | title = Do equivalent doses of escitalopram and citalopram have similar efficacy? A pooled analysis of two positive placebo-controlled studies in major depressive disorder | journal = Int Clin Psychopharmacol | volume = 19 | issue = 3 | pages = 149–55 |date=May 2004 | pmid = 15107657 | doi = 10.1097/00004850-200405000-00005 | s2cid = 36768144 }}</ref><ref>{{cite journal|last=Hyttel|first=J.|author2=Bøgesø, K. P. |author3=Perregaard, J. |author4= Sánchez, C. |title=The pharmacological effect of citalopram resides in the (''S'')-(+)-enantiomer|journal=Journal of Neural Transmission|year=1992|volume=88|issue=2|pages=157–160|doi=10.1007/BF01244820|pmid=1632943|s2cid=20110906}}</ref>
* '''Drug safety:''' [[Penicillamine|<small>D</small>‑penicillamine]] is used in [[chelation therapy]] and for the treatment of [[rheumatoid arthritis]] whereas <small>L</small>‑penicillamine is toxic as it inhibits the action of [[pyridoxine]], an essential B vitamin.<ref>{{cite journal|last=JAFFE|first=IA|author2=ALTMAN, K |author3=MERRYMAN, P |title=The Antipyridoxine Effect of Penicillamine in Man.|journal=The Journal of Clinical Investigation|date=Oct 1964|volume=43|issue=10|pages=1869–73|pmid=14236210|doi=10.1172/JCI105060|pmc=289631}}</ref><ref>{{cite journal |last1=Smith |first1=Silas W. |title=Chiral Toxicology: It's the Same Thing...Only Different |journal=Toxicological Sciences |date=July 2009 |volume=110 |issue=1 |pages=4–30 |doi=10.1093/toxsci/kfp097 |pmid=19414517 |doi-access=free}}</ref>

As such enantioselective synthesis is of great importance but it can also be difficult to achieve. Enantiomers possess identical [[Enthalpy of formation|enthalpies]] and [[Entropy|entropies]] and hence should be produced in equal amounts by an undirected process – leading to a [[racemic]] mixture. Enantioselective synthesis can be achieved by using a chiral feature that favors the formation of one enantiomer over another through interactions at the [[transition state]]. This biasing is known as [[asymmetric induction]] and can involve chiral features in the [[Substrate (chemistry)|substrate]], [[reagent]], [[catalyst]], or environment<ref>{{GoldBookRef|title=asymmetric induction|file = A00483}}</ref> and works by making the [[activation energy]] required to form one enantiomer lower than that of the opposing enantiomer.<ref>{{Clayden}}Page 1226</ref>

Enantioselectivity is usually determined by the relative rates of an enantiodifferentiating step—the point at which one reactant can become either of two enantiomeric products. The [[rate constant]], ''k'', for a reaction is the function of the [[activation energy]] of the reaction, sometimes called the ''energy barrier'', and is temperature-dependent. Using the [[Gibbs free energy]] of the energy barrier, Δ''G''*, means that the relative rates for opposing stereochemical outcomes at a given temperature, ''T'', is:

:<math>\frac{k_1}{k_2} = 10^\frac{\Delta \Delta G^*}{T \times 1.98 \times 2.3}</math>

This temperature dependence means the rate difference, and therefore the enantioselectivity, is greater at lower temperatures. As a result, even small energy-barrier differences can lead to a noticeable effect.

:{| class="wikitable"
|-
! ΔΔ''G''* (kcal)
!colspan=2 |{{sfrac|''k''<sub>1</sub>|''k''<sub>2</sub>}} at 273&nbsp;K
!colspan=2 |{{sfrac|''k''<sub>1</sub>|''k''<sub>2</sub>}} at 298&nbsp;K
!colspan=2 |{{sfrac|''k''<sub>1</sub>|''k''<sub>2</sub>}} at 323&nbsp;K)
|-
| style="text-align:center;" | 1.0
| {{decimal cell|6.37}}
| {{decimal cell|5.46}}
| {{decimal cell|4.78}}
|-
| style="text-align:center;" | 2.0
| {{decimal cell|40.6}}
| {{decimal cell|29.8}}
| {{decimal cell|22.9}}
|-
| style="text-align:center;" | 3.0
| {{decimal cell|259}}
| {{decimal cell|162}}
| {{decimal cell|109}}
|-
| style="text-align:center;" | 4.0
| {{decimal cell|1650}}
| {{decimal cell|886}}
| {{decimal cell|524}}
|-
| style="text-align:center;" | 5.0
| {{decimal cell|10500}}
| {{decimal cell|4830}}
| {{decimal cell|2510}}
|}