Talk:Enantioselective synthesis

Proposal to rename

I propose that this article be renamed asymmetric synthesis, which is (in my experience) the more usual term. Are the two terms completely synonymous, as I believe, or is there some subtle difference I'm unaware of? A Google search gives around 400,000 hits for "asymmetric synthesis", which is ten times the number found for "chiral synthesis". Comments, anyone? Walkerma 05:51, 6 March 2006 (UTC)

Agreed. Chirality is a property of a compound, object, or geometrical construct. Other comments about the article:

- would more clearly define asymmetric synthesis as the production of one enantiomer of a desired compound, rather than a racemate. - the approach where one starts from a cheap, naturally available material is called the "chiral pool" approach - the diagram is odd. perhaps a more conventional wedged and dashed bond diagram? - the term "chiral catalysis" is unusal. the more typical term is "catalytic, asymmetric", with the same arguments applying to catalysis as synthesis. it may, or may not be more efficient than the chiral pool approach, depending on a number of factors. for example, one enantiomer of the ligand may be very expensive. - synthesis of a racemate, followed by resolution, should probably be considered a form of asymmetric synthesis, although this process is not made clear in the article - the term "Sharpless bishydroxylation" is unusal; more typically, one sees it referred to as a "dihydroxylation" - the mechanism of how chiral ligands works is vague. i recommend not mentioning the mechanism of action at all. there may be electronic factors at work at well. see the review on the conservation of helicity at phil baran's webpage at scripps. - epimerization does not necessarily occur through an isotropic intermediate; SN1 reactions may proceed via a planar carbocation, but this does not mean the molecules itself becomes planar; SN2 substitution may or may not invert the chirality--there may be no chirality to begin with - there need to be more examples to illustrate the points made in this article, preferably with chemdraw schemes Eugene Kwan 16:32, 6 March 2006 (UTC)

Asymmetric synthesis is by far a more common term than chiral synthesis (and more precise too) among those that actually do asymmetric synthesis. As to Eugene's comments, they all sound like great suggestions to me. They should be incorporated into the article. Edgar181 18:29, 8 March 2006 (UTC)

I'll request a move (can't move because of the redirect) --Rifleman 82 03:19, 1 December 2006 (UTC)

Page moved. Cheers. -GTBacchus^(talk) 04:36, 1 December 2006 (UTC)

From the words of Eliel...

"Asymmetric Synthesis. This term is probably too deeply embedded in the chemical nomenclature to be eradicated. Nonetheless two problems with this term should be pointed out. First of all, the term, in its most general sense, applies to dissymmetric (or, as we now say, chiral) reagents, catalysts, products, and chiral auxiliaries. In fact, some of the most effective chiral auxiliaries have C2 symmetry, i.e., they are not asymmetric at all! Secondly, of course, it is the catalysts, products, etc., that are chiral (not necessarily asymmetric!), not the syntheses as such. (We shall find this kind of wrong apposition in many of the other examples below.) The proper term to use, in lieu of "asymmetric synthesis" would be "enantioselective synthesis" (if one of two enantiomers is produced in predominance) or, in some cases, "diastereoselective synthesis" when one of two or more diastereomers is produced predominantly. (This, also, has been called an asymmetric synthesist i.e., when both starting material and product are enantiopure or enantioenriched, for example in the hydride reduction of cholestanone to 33-cholestanol where a new chiral center is introduced stereoselectively at C(3). Such dual use of "asymmetric synthesis" is, in this author's opinion, confusing.)"

Eugene Kwan 05:20, 21 January 2007 (UTC)

I'm guessing you are quoting from [http://www.amazon.com/Basic-Organic-Stereochemistry-Ernest-Eliel/dp/0471374997/sr=1-2/qid=1169357116/ref=sr_1_2/102-9306392-1519307?ie=UTF8&s=books this Eliel], is that right? While I can see his points, we all know that chemistry in general (and organic chemistry in particular) has the most confusing naming systems and cunventions. I have always taken the term "asymmetric synthesis" to be shorthand for "the synthesis of an asymmetric product in enantiomerically pure or enriched form." OK, maybe we should say dissymmetric to be precise, but we're stuck with the rather sloppy term that is widely used. Wikipedia follows the name that is widely used, not the one we might like to have instead! Walkerma 05:35, 21 January 2007 (UTC)

I quote Eliel purely for interest's sake, not to suggest any nomenclature eradication. Eugene Kwan 00:56, 23 January 2007 (UTC)

Mistake in the structure of DiPAMP, in Knowles' L-DOPA Synthesis

There is a serious mistake in the reaction scheme of the L-DOPA synthesis. DiPAMP is a diphosphine, in which the chirality is actually born by the Phosphorus atoms. In the current drawing, the chirality was mistakenly drawn as born by a supplementary neighbouring atom. I enclose a new PNG drawing, send me your suggestions.

comment was added by AlChimini (talk) 11:20, 18 May 2008 (UTC)

Have incorporated the change, let me know what you think of it. Cheers! comment was added by AlChimini (talk) 12:38, 24 May 2008 (UTC)

Thanks! I'm on holiday and can't check the literature, but I'm pretty sure you're right. I'll let V8rik know, to confirm it. Cheers, Walkerma (talk) 23:16, 25 May 2008 (UTC)

see [1] in [2] which seems at least to be now the correct structure of the ligand -- Quantockgoblin (talk) 00:51, 26 May 2008 (UTC)

Thanks for your feedback, guys. What do You think of the idea of creating a new category "chiral ligands", probably as a subcategory of "organometallic chemistry" and starting a series of short pages on the most important chiral ligands for this subcategory, with their enantioselective synthesis and a list of references for some examples of their uses (pages for BINAP, BINOL, BOX already exist. In my opinion, deeply missed are the oxaborolidine ligands for CBS reduction, TADDOL, DIOP, DIAB, DuPhos, the Solvias MandyPhos and TaniaPhos, Buchwald's X-Phos, Helmchen's ligands, the Bolm ferrocenyl ligands... and probably many more). Do You think there is an audience for this? Anyway, I'd like to try and start working on it anytime soon. If anybody wants to collaborate, let me know... comment added by AlChimini (talk) 08:48, 26 May 2008 (UTC)

Sounds like a great idea, it would be great to cover these ligands, in fact I'm a little surprised there is such a gap on wiki in this regard ... sounds like you're the chap to get the ball rolling on this! Thanks and happy editing -- Quantockgoblin (talk) 10:17, 26 May 2008 (UTC)

Yes, it sounds good to me. Walkerma (talk) 20:46, 26 May 2008 (UTC)

confusing paragraph

The following paragraph is confusing:

For example, a SN1 substitution reaction converts a molecule that is chiral by merit of non-planarity into a planar molecule, which has no handedness. (To visualise, draw the outlines of both of your hands on paper, and cut the images out. You can now superimpose the images, even if the hands themselves do not superimpose.) In a SN2 substitution reaction on the other hand the chirality inverts, i.e. when you start with a right-handed mixture, you'll end up with left-handed one. (A visualization could be inverting an umbrella. The mechanism looks just the same.)

Explanation:

SN1 generates a racemate (mixture of chiral, *nonplanar* molecules), and the "planar molecule" (carbocation) is only a transient species. The word "mixture" in the following sentence about SN2 should rather be replaced with "molecule"/"system"/"compound". —The preceding unsigned comment was added by 87.105.129.208 (talk) 20:48, 17 February 2007 (UTC).

Garbled English

What is meant by "trajectory" in the second paragraph?

Asymmetric induction can also occur intramolecularly when given a chiral starting material. This chirality transfer can be exploited, especially when the goal is to make several consecutive chiral centers to give a specific enantiomer of a specific diastereomer. Aldol reaction, for example, is inherently diastereoselective; if the aldehyde is enantiopure, the resulting aldol adduct is diastereomerically and enantiomerically pure.

One such strategy is the use of a chiral auxiliary which forms an adduct to the starting materials and physically blocks the other trajectory for attack, leaving only the desired trajectory open. Assuming the chiral auxiliary is enantiopure, the different trajectories are not equivalent, but diastereomeric.

77.98.79.252 02:24, 29 March 2007 (UTC)

Nothing fancy here, just the usual meaning of trajectory: the direction or path of motion. DMacks 02:28, 29 March 2007 (UTC)

William S. Knowles

According to the Nobel info Knowles was the first with chiral ligands in 1968. I have also been reading other articles completely ignoring Knowles so I am wondering what is going on. The article

Design of chiral ligands for asymmetric catalysis: From C2-symmetric P,P- and N,N-ligands to sterically and electronically nonsymmetrical P,N-ligands Andreas Pfaltz and William J. Drury III PNAS, April 20, 2004 vol. 101 no. 16 5723-5726 doi:10.1073/pnas.0307152101

credits Kagan (1972) as the originator and continues

The design principles that led Dang and Kagan to this ligand had a marked influence on the course of research in asymmetric catalysis, and many diphosphine ligands that were introduced subsequently were patterned after DIOP. Knowles (7), for example, prepared a dimeric analogue of one of his previously synthesized monophosphines, which he termed DiPAMP

with a reference (7) from 2003 (!). Is this a falsification of history? V8rik 22:15, 28 July 2007 (UTC)

As I recall, Bredig provided the earliest known example of asymmetric catalysis, when he used cinchona alkaloids to catalyse the asymmetric synthesis of cyanohydrins. I don't have the original reference, but Trost discusses it in Proc Natl Acad Sci USA 2004, 101, 5348-5355.

Knowles' prize was for catalytic asymmetric hydrogenation, NOT asymmetric catalysis in general. Ziqquratu (talk) 06:24, 14 October 2010 (UTC)

Willy Marckwald

Willy Marckwald lifed from 1864 til 1942. Willy Marckwald discovered Polonium in 1902 and called it radio­tellurium.

• Rassow (1925). "Willy Marckwald zum sechzigsten Geburtstage, gewidmet von Freunden und Schülern. 5. Dez. 1924. Verlag Chemie, G. m. b. H., Leipzig-Berlin". Zeitschrift für Angewandte Chemie. 38 (22): 508. doi:10.1002/ange.19250382213.
• H. W. Kirby (1971). "The Discovery of Actinium". 62 (3): 290–308. {{cite journal}}: Cite journal requires |journal= (help)
• doi:10.1524/ract.2000.88.3-4.123doi:10.1002/cber.190603901118doi:10.1038/070627a0doi:10.1002/cber.19340670647doi:10.1002/cber.19380710515

Asymmetric ester hydrolysis with pig-liver esterase

There is an article on asymmetric ester hydrolysis with pig-liver esterase. It's an orphan article. I'm a high school dropout and can understand basically nothing in either articles, but does someone know of a place to mention asymmetric ester hydrolysis with pig-liver esterase in this article so that it is no longer an orphan? Thank you. Ceaseless (talk) 08:57, 15 January 2013 (UTC)

• Done! V8rik (talk) 17:56, 15 January 2013 (UTC)

Clean-up/rewrite?

I feel this page is in need of a clean-up as it and includes information which doesn't really belong here and links to several niche articles without providing much context (unbalanced?). For example chiral pool synthesis isn't really a form of enantioselective synthesis; you're not creating any new enatiomers, you're just retaining them. This is only my opinion though and I'm not going to make major edits without checking with others. I've written up and new version of the page here, feedback of any sort is very welcome. Project Osprey (talk) 15:20, 12 February 2013 (UTC)

• The whole section Enantioselective catalysis has vanished in your proposal. Also, if you want to exclude chiral pool synthesis here, at what point in the information tree should it be introduced? V8rik (talk) 18:27, 12 February 2013 (UTC)

The section has been separated into its component methods so all that's vanished is the title "Enantioselective catalysis" and 3 historical references. Frankly I don't see that they belong here but once you remove them there's virtually nothing left on enantioselective metal catalysis, so that section has actually been expanded somewhat. I see your point on chiral pool synthesis but strictly speaking it isn't a type of enantioselective synthesis (at least not as IUPAC define it). A section on alternative methods might be an idea though? Project Osprey (talk) 23:52, 12 February 2013 (UTC)

I do not see why the historical references should be removed. You also removed the image of an example of an enantioselective synthesis top right in your proposal. Like having an article on bicycles without showing any image of a bicycle. We agree on the chiral pool synthesis bit but how do we make sure people will still find a reference to it? With respect to niche topics: any article should start with the basics and then move to details or have links to more specialised articles. So links to what you call niche articles are perfectly acceptable. With respect to balanced content you seem to have misconceptions. The bicycle article does mention unicycles for a good reason. V8rik (talk) 22:22, 13 February 2013 (UTC)

You're right, perhaps I was hasty to remove the history. My desire was to give an at-a-glance view of the topic by giving a simple but concise description of each process. My motivation being a presumption: I think that a lot of people reading this page will be novice chemists. Context is always of use though, so I shall try to add the following sections to my draft.

1. A brief history of enatioselective synthesis: So that we're telling the 'why' as well as the 'how'. Be warned however; it will probably focus on pharmacuticals a lot (Thalidomide etc)
2. A section on alternative methods: Chiral pool, chiral resolution etc.
3. A section on the analysis of enatiomers: A overview of the difficulties and solutions

Does that seem better to you? Project Osprey (talk) 13:49, 14 February 2013 (UTC)

• thanks for your consideration, I am looking forward to the end result V8rik (talk) 21:35, 14 February 2013 (UTC)

I disagree. I would say that if classifying different types of synthesizing enantiopure materials, then chiral resolution and chiral pool synthesis would be in the list. There is a difference between "enantio-agnostic" and enantioselective synthesis even if the starting material is already enantiopure, because each subsequent step must be diastereoselective. The chiral centers are often modified and possibly inverted, for instance, consider the commercial oseltamivir synthesis. I would say that it's a distinction in a very technical sense only if one understands "enantioselective synthesis" only as a synthesis step where asymmetric induction is accomplished. On the other hand, in the interest of limiting article length, parts should be separated if the article grows too long. The article has developed a lot since I started it, to a considerable improvement. -- vuo (talk) 13:21, 15 February 2013 (UTC)

• Thanks for joining the discussion Vuo. Interesting question: is the Oseltamivir synthesis an example of enantioselective synthesis? You have to preserve the chiral centres throughout the sequence. I would agree. I would not agree that chiral resolution is a type of enantioselective synthesis. And why drag in thalidomide? It is one of those urban chemistry myths anyway (http://www.nature.com/nchem/journal/v2/n8/full/nchem.750.html). In terms of the information tree, some content should be handled by the chirality article, more specialized content by the enantiomer article and even more specialized content by articles such as enantioselective synthesis and chiral resolution. V8rik (talk) 22:50, 16 February 2013 (UTC)

• As I understand it; it took a while for the debate surrounding the potentially tetrogenic enantiomer of thalidomide to be settled. This resulted in the rules for drugs being tightened to encourage enantio-pure products, just be be on the safe side. So to that extent it seems worth mentioning, even if the theory was wrong (this is just what I've been told though, if I can't find the right references I'll drop it). With regards to chiral pool synthesis; I do see your point. Inversion or modification of a pre-existing stereocentre, like in an S_N2 reaction, can clearly be enatioselective. However this is different from processes where a new stereocentre is generated via asymmetric induction. As it stands I'm simply going to place the 2 types into separate sections. Project Osprey (talk) 02:08, 17 February 2013 (UTC)

Second draft now ready (here); apologies for the long delay. For comparison the first draft is here. I've done my best to address the points raised last time but if people still have major issues then I'll probably just stop here. Project Osprey (talk) 11:09, 21 April 2013 (UTC)

• I am happy with it, I am glad to see the Nobel Prize winning work made it into the new version. V8rik (talk) 14:01, 21 April 2013 (UTC)

New version transfered across. Links to my sandbox now have been removed. Project Osprey (talk) 13:05, 1 May 2013 (UTC)