Talk:Asymmetric transfer hydrogenation

Proposed BINAP-Ru scheme[edit]

The newly proposed BINAP-Ru scheme (1:1 replacement of existing one) was deemed to large and with errors. Size can be remedied like below. I have checked both versions and can find no immediate errors. I am used to clockwise cycles?. V8rik (talk) 21:02, 3 July 2014 (UTC)[reply]

BINAP-Ru catalytic pathway	BINAP-Ru catalytic pathway stereoselectivity

These issues come to the mind of an organometallic chemist:

1) As is normal for Ru, this catalyst hydrogenates without change in oxidation state, but this scheme invokes Ru(I) as the products of steps C and D.
2) it would probably be more instructive to show stepwise transfer of hydride in the enantioselecting step, followed by separate hydrogenolysis of the Ru-alkoxide to regenerate the starting hydrido chloride. The scheme invokes coupled protonation and hydride transfer.
3) In the current scheme, catalyst regeneration is achieved by addition of H dot. Often sign of a problem.

Picky things that might bother experts:

H2 generates the pro-catalyst by hydrogenolysis of a Ru-Cl bond. H2 then is consumed catalytically. The double arrow from H2 is confusing because it implies that both reaction channels consume H2 comparably, but they don’t of course. Double arrows, except in the case of resonance structures, confuse to non-experts and are distracting to experts.
~~typically ketone hydrogenation (vs transfer hydrogenation) proceeds via h²-ketone, not O-bonded ketones as invoked here. Otherwise the hydride can’t reach the carbon.~~

Most generally:

A mechanistic review doi:10.1016/j.ccr.2004.04.007 is more circumspect about the mechanism than the scheme above. So to me, the above scheme verges on original research or conjecture, intriguing nonetheless.
My guess (only that) is that the Ru(BINAP)HCl(solv)2 and BINAPRuX2(diamine) systems have been eclipsed by the cymeneRu(TsDPEN) system. The latter, like the diamine catalyst, operates by transfer hydrogenation. The Ru-TsDPEN system probably merits mention.--Smokefoot (talk) 02:34, 8 July 2014 (UTC)[reply]

Thank you for your comments. The original mechanism suffers from many of the same problems, then, yes? I don't have access to the article (getting it through interlibrary loan, soon), what changes can we make to the mechanism to make both the original and the redesign mechanistically accurate? I did wonder about the distance and hydride reaching the carbon, but assumed the original mechanism to be accurate.Azmanam (talk) 13:37, 8 July 2014 (UTC)[reply]

Well, I dont think that the mechanism needs the BINAP shown since it does not change throughout the cycle: the resulting Ru-H catalyzed hydrogenation, the resulting image would be more compact. I agree that the eta-2 ketone is not typically shown. The bigger issue is that this is one of three (that I know of) major catalyst types invented by the Nagoya group. --Smokefoot (talk) 13:55, 8 July 2014 (UTC)[reply]

I compared the scheme above with the one described by Noyori in a 2001 review (doi:10.1002/1521-3773(20010105)40:1<40::AID-ANIE40>3.0.CO;2-5) and I would say it is 100% consistent. Quoting from the review:

"Scheme 3 presents our proposed mechanism for the asymmetric reaction of b-keto esters.[10c] The hydrogenation probably proceeds via a RuII monohydride 2 formed by the heterolysis of a hydrogen molecule by the ruthenium dichloride 1. The Ru hydride 2 interacts reversibly with the keto ester to form the chelating complex 3. Protonation of the keto oxygen changes the geometry of 3 from the s to the p complex and, at the same time, increases the electrophilicity of the carbonyl carbon, facilitating intramolecular hydride transfer.[ 25, 26] The resulting Ru ± hydroxy ester complex 4 readily releases the chiral product by the action of solvent molecules. The cationic ruthenium species 5 reacts with hydrogen to revert back to 2, completing the catalytic cycle" V8rik (talk) 11:44, 19 July 2014 (UTC)[reply]

Thanks for sticking with this issue and thanks for the citation to the Noyori and Ohkuma (N&O) review. Great diligence. The main problem, as indicated in my opening remarks above, is oxidation states. Oxidation state is a big deal to the organometallic folks, but you can see from their review that the focus is on products not mech, that is the reason that a more organometallic review for those interested in details. Even N&O are careful oxidation states as indicated by charge on the proposed intermediates. N&O follow various presentation aspects that might be useful style guides, like not drawing huge ligands in each step, avoiding double arrows. But those aspects are a matter of taste. Cheers, --Smokefoot (talk) 15:48, 19 July 2014 (UTC)[reply]

Desire to get this article to C-class standard.[edit]

I am interested in getting this article to a C-Class standard. I plan to work on it in the coming days. @Smokefoot you seem to be active on this page so I would appreciate running certain edits here by you first to avoid reverts.

I see that in the past there have been several reverts on discussions concerning BINAP ligands. Could you elaborate a bit more why these were unwelcome? I do believe there is sufficient literature on the mechanism to justify a greater discussion of their effects.

Balonlon (talk) 09:08, 28 November 2023 (UTC)[reply]

Step 1: determine the scope and definition of the topic. There is no "Noyori asymmetric hydrogenation" as I tried to explain to hard-headed V8rik many years ago. There are:

asymmetric hydrogenation, a topic where Noyori contributed
transfer hydrogenation, another topic where Noyori contributed

Let me move this imperfectly titled article to asymmetric transfer hydrogenation. Then we're good. --Smokefoot (talk) 14:28, 28 November 2023 (UTC)[reply]

Hey @Smokefoot, glad to see your speedy reply.

I agree, I see you have already gone ahead and moved the page over. I also see that Asymmetric hydrogenation is quite a well written article already. I will also put some comments on it's talk page separately.

With regards to ATH (asymmetric transfer hydrogenation), if my understanding is correct, the difference between them is such that in this case the proton transfer refers to the specific formation of a hydride and a proton by the metal complex from a source that is no H2, followed by a hydrogenation of the C=X bond (X being a hetero-atom). The difference with AH is that in AH there is a direct hydrogenation of the C=C (or occasionally C=X) bond with diatomic hydrogen. If you agree with this distinction, then I can move on to some more concrete re-writes to the article.

That said, looking at transfer hydrogenation raises the question of the need for this page in the first place. It would appear that between them they cover the topic quite well?

Balonlon (talk) 14:56, 28 November 2023 (UTC)[reply]

It may take you a while to figure out the landscape because a lot of articles may exist on related topics. But it is worthwhile looking around. For example, there is this thing Enantioselective reduction of ketones, which is not so great. In addition to these "methods" articles, there are articles on individual catalysts and ligands. ATH is a subset of asymmetric hydrogenation (AH), i.e. they are both asymmetric and both hydrogenation. AH and ATH are always implementations of homogeneous catalysis. Usually AH uses H2 and acts on C=C. ATH uses alcohols (usually) as sources of H2 and mainly focuses on polar bonds like C=O and C=N. Noyori was a big player in both topics, but there were many big players. Anyway readers are not interested in personalities, but in the science and technology. I agree that ATH might be usefully merged into transfer hydrogenation (TH).

--Smokefoot (talk) 15:17, 28 November 2023 (UTC)[reply]

Looking at the page as it stands now the last comment appears even more so of relevance. All pictured reactions use H₂ as the hydrogen source. The whole principle of transfer hydrogenation is that it is taken from an alternative source. To me, this suggests a need to transfer a lot of the contents of this article to the "Platinum-group metals" section of the Asymmetric hydrogenation article and then either commit to writing this page from scratch based on other examples or to remove it altogether.

I also agree that expanding the section relating to ATH on the transfer hydrogenation article is something that can be done. Specifically, under the section "Organometallic catalysts".

Balonlon (talk) 15:21, 28 November 2023 (UTC)[reply]

The plan would be to move almost all the content from this article into AH. The material dealing with H2.

Then the small mechanism section would move to TH

Finally Asymmetric transfer hydrogenation would be converted into a redirect to Transfer hydrogenation, which would have a section on the asymmetric version.

--Smokefoot (talk) 15:51, 28 November 2023 (UTC)[reply]

@Christian75 I appreciate that you've (plural) already re-linked the page but it would have been nice if you had waited a bit so I could have more easily accessed it while determining which parts need to move there. That's ok, I'll just use the archived versions I guess... Balonlon (talk) 12:04, 29 November 2023 (UTC)[reply]

Relinked what page? Christian75 (talk) 12:14, 29 November 2023 (UTC)[reply]

Sorry I'm catching up with the change logs now. It's more @Smokefoot that I need to talk to about this, sorry for tagging you. Balonlon (talk) 12:17, 29 November 2023 (UTC)[reply]