Talk:Flippin–Lodge angle

Untitled

The Burgi-Dunitz entry has beautiful diagrams. Any chance that this entry could get similar treatment? —Preceding unsigned comment added by 89.243.31.97 (talk) 15:55, 14 January 2011 (UTC)

Not improved

This

The Flippin-Lodge angle is the lateral angle of nucleophilic attack to a carbonyl or similar, i.e. in the same plane as the carbonyl and its substituents, when Bürgi-Dunitz angle is the angle in the perpendicular plane.

Stereoselectivity increases with a lower Flippin-Lodge angle, which is determined by the steric bulk of the substituents of the carbonyl. Thus, aldehydes have lowest selectivity, and tert-butyl ketones highest.

was replaced by this

The Flippin-Lodge angle is one angle of attack of a nucleophile on a carbonyl, R1-C(O)-R2, or related pi system, that, with the Bürgi-Dunitz angle fully describes the angular geometry of that attack.

One can describe a vector that is created by the reactive atom of the nucleophile, Nu:, and the carbonyl carbon. The Bürgi-Dunitz angle describes the angle made between this vector and the plane determined by the carbonyl >C=O and its R1 and R2 substituents; specifically, it is the Nu-C-O angle where C-O lies in the described plane. This angle is theorized and observed to be an obtuse angle (>90 deg), originally set at 105 +/- 5 deg, with more recent estimates set at 107 deg. This angle, sometimes referred by the Greek letter theta, can be understood as a measure of the degree to which the attack of the nucleophile is necessarily offset from directly above (i.e., perpendicular to) the carbonyl carbon in its plane, for reasons arising from the molecular orbitals of nucleophile and carbonyl.

A further line can be described which contains the C=O bond of the carbonyl, and therefore lies in the plane described above; this line bisects the R1-C-R2 angle of the carbonyl. The Flippin-Lodge angle is the angle between a projection onto the R1-C(O)-R2 plane of the Nu-C vector (described above) and this line bisecting the R1-C-R2 angle of the carbonyl. This angle, sometimes referred by the Greek letter psi, can be understood as a measure of the degree to which the attack of the nucleophile is offset toward R1 or R2 from directly behind the carbonyl carbon (i.e., offset from the second, perpendicular plane also containing the C-O bond of the carbonyl). The reasons for such offset lie in attractions and repulsions (steric, electrostatic) between the nucleophile, and the R1 and R2 substituent structures.

For images making this description clearer, the reference should be consulted.

while deleting the main motivation used by Flippin and Lodge, namely differences in stereoselectivity, as "inaccurate". If there's no objection, I'll simply revert this. What is really necessary is a diagram. --vuo (talk) 22:53, 8 February 2011 (UTC)

I undid a edit made by Dr Lee Flippin yesterday because I thought it was just vandalism, but it is their opinion that the tag could be removed now. I'm do not know the material, but I wanted to make sure that their opinion was involved as it might be valuable. They also left an explanation for this on my talk page that is way above my head if you wanna hear their argument. Cafkafk (talk) 11:11, 12 September 2021 (UTC)

Status of article, and need for F-L figure

The original two line text describing the Flippin–Lodge angle was ambiguous -- lateral is not a description that makes sense in describing chemical trajectories in three dimensions.

The long description that I wrote is accurate but is admittedly somewhat difficult to follow; it was introduced **in lieu of a figure** to clearly describe the BD and FL planes and angles. I fully agree that a figure is needed. See below regarding known figures; I invite people with knowledge of this area to broadcast, here, if other good FL figures exist.

The two published figures of which I am aware (Jan 2012) -- apart from anything in the original, older literature -- are (a) the simple one in the teaching text of Ian Fleming at Cambridge that is currently cited in this article, which is the simplest figure, in a text that provides best chemical teaching context and is also well referenced, and (b) that of Radisky and Koshland, Jr, in a biochemical context, which uses the concept but fails to identify the angle as FL, or to cite relevant literature (PNAS 2002, 99:10316–10321). Neither figure is in the public domain.

Apart from the paucity of available figures, there is a nomenclature issue. Fleming's representation uses theta and psi for the BD and FL angles, respectively. Psi, for its various other uses, including in Ramachandran-type dihedrals, makes its application here an unfortunate choice, and I am not going to propagate it further (though I wrote psi it into this Wiki text). Koshland's use of theta-sub-x and theta-sub-y are, unfortunately, geometrically ambiguous (as well as being unattached, in a scholarly sense, to the FL literature). This needs to be resolved in the primary literature, and I am in the process of contributing something that will do that.

As well, I am currently working on a figure based on FL and BD original figures, and on Fleming and Koshland (for a publication related to my and my collaborators research). I intend that the figure will go in the public domain before I submit the manuscript for publication (which will result in the manuscript's figures and other content being copyrighted). If this is possible, there will be a good BD and FL figure, soon in Wikipedia. THEN, we can remove the long descriptive text that currently appears (which, while accurate, is not as an effective a tool as the good figure will be).

Reiterating, I strongly encourage people with knowledge of this area, to let everyone if other good FL figures exist. Meanwhile, I hope my "day job" will produce one that is useful. Prof D. Meduban (talk) 17:07, 20 January 2012 (UTC)

I've done a simple diagram in the mean time, just so readers know what angle we're talking about. It's based on Ian Fleming's book. --Ben (talk) 21:24, 20 January 2012 (UTC)

Explanation of tags, and general good and welfare

Four closing points: (1) I added a tag calling for references to the stereoselectivity paragraph, because, after searching in the one article reference (Fleming), I could not find the information in that article. Unless I am mistaken, it is not on pages 214-215, and perhaps is not in Fleming at all. This needs to be rectified, hence the tag. (2) The same paragraph is well-written, but because of time, I could not review for content accuracy. Will do this after the reference appears. (3) Encourage continuing review of this section, to improve quality (but with citation, to make expert editing efficient vis-a-vis time). (4) Generally, propose we stay away from titles that present an individual's judgement regarding quality. I find that imprecise language regarding geometric descriptions of reaction trajectories to be unhelpful. Another finds careful description of geometries to be unhelpful. Neither need be stated; we agree that a picture is worth many words, and time is best spent creating or finding that picture (see preceding and next talk sections). Prof D Meduban (talk) 18:31, 20 January 2012 (UTC)

Further helpful Flippin-Lodge citation, including with regard to stereoselectivity of reactions

RE Gawley and J Aube, 1996, Principles of Asymmetric Synthesis (Tetrahedron Organic Chemistry Series, Vo. 14), pp. 121-130, esp. pp. 127f.

http://books.google.com/books?id=-T3l1Me9LrMC&pg=PA128&lpg=PA128&dq=%22Flippin-Lodge%22+angle&source=bl&ots=EPP1OE22FN&sig=YmSipTvymjFDcsEdF2HZREHYSPU&hl=en&sa=X&ei=X6wZT7TmJc_yggfMzajUCw&ved=0CCAQ6AEwADgK#v=onepage&q=%22Flippin-Lodge%22%20angle&f=false

Perusal of this reference, which is in itself dated, suggests the last paragraph as it exists in the article is inaccurate, taking only into account steric effects, and ignoring orbital interactions. In short, there appears literature and text infomration which indicates the generalizations in this paragraph to be only applicable to limited cases.

Meduban (talk) 18:41, 20 January 2012 (UTC)

Changes to FL article, where response is invited

Ben, vuo, please review the changes made. Also open the BD article, and look at the parallel construction.

The verbosity, especially in the figure legend, is because of the 3D nature of the FL, versus the 2D appearance and implications of the current figure (without any clarifying explanation).

Have a look at the Aldrichimica Acta article for the way CHH presented this angle in the article where he coined the term -- the system is viewed on-edge of the carbonyl plane, down the C=O bond; his is the way I am presenting this in a MSS going in this month.

In re: nomenclature, CHH declined to weigh in (too fully beyond it, he said), but was encouraged by Prof IF in efforts to clarify the use of the BD and FL nomenclature -- both as representing **observations in each system** and not ideals, and vis-a-vis the symbol used -- in our upcoming MSS's (and so it appears here). The matter of the angles representing **observations** rather than a theoretical ideal has always been more obvious for the FL than the BD, so it will potentially be more controversially there. In terms of nomenclature, we'll publish soon listing the BD as alpha-sub-BD (to return to the alpha used by B & D), and accordingly, will use alpha-sub-FL for this angle. Others being consulted, let you know how they respond.

Ben, please consider contacting me, at my wiki login name (7 characters, m.....n, plus ATnorthwestern.edu, soon, and perhaps you can help me translate even better pictures into this and the BD article.

Any change in chemistry substance, let's chat. Note the book section by Jeff Aube (probably visible on Amazon) could be summarized to close this article. But we need tight language, specific language about diastereoselection, tied to reference. Enough garbage descriptions are about, and noone has time to check descriptions not based on reference. Base ours on the best -- original papers or books like Jeff's.

As for any desired change to format and wiki-suitability -- have at it. Prof D. — Preceding unsigned comment added by 67.173.94.53 (talk) 20:08, 16 June 2012 (UTC)

diastereoselection redact, to request more work

Guys, this paragraph, which has been unreferenced since appearing...

Stereoselectivity of attack on α-substituted ketones increases with a lower Flippin–Lodge angle, which is affected by the steric bulk of the substituents of the carbonyl. Thus, aldehydes with the highest Flippin–Lodge angle have lowest selectivity, and tert-butyl ketones the highest selectivity with the smallest Flippin–Lodge angle. Aldehydes have a hydrogen substituent that produces the least steric hindrance, occluding the least space on the syn face of the ketone, allowing for higher Flippin–Lodge angles of attack, resulting in more syn attack and lower syn:anti selectivity. In contrast, a bulky substituent such as tert-butyl occludes more space around both faces, which keep the Flippin–Lodge angle small; this trajectory is much more sterically hindered on the syn face than in an aldehyde, resulting in higher syn:anti selectivity.

...doesn't make easy, clear sense to me as a practicing chemist and prof (and introduces nomenclature without pictures). Can you have another pass at it, connecting more directly with Aube, or Heathcock, or some relevant ref, and then stick it back in? In particular, I'd recommend reading:

• what i wrote to simplify huge swaths of observations,
• E.P. Lodge & C.H. Heathcock (1987) Steric effects, as well as sigma*-orbital energies, are important in diastereoface differentiation in additions to chiral aldehydes, J. Am. Chem. Soc., 109:3353-3361.
• RE Gawley and J Aube, 1996, Principles of Asymmetric Synthesis (Tetrahedron Organic Chemistry Series, Vo. 14), pp. 121-130, esp. pp. 127f.
• and articles citing these, or any other reputable source you can find that is more recent (harvard/scripps notes particularly good, if up to date).

... before trying a one paragraph summary of these complex issues. Cheers.

Nucleophile side: Heathcock and Flippin discussed the attack of an R2-enolate on an α-methyl-R1-aldehyde. It was found that the larger (sterically) the enolate structure is, the more selective the reaction is; the best enolate was the TBDMS enolate from t-butyl acetate. Lithium enolates were an order of magnitude less selective. 10.1021/ja00344a050

Carbonyl side: Lodge and Heathcock explained the observation that when asymmetric (α-methylbenzyl)(R)ketones were reduced by lithium aluminium hydride, the selectivity of α-methyl-hydroxyl being syn was a function of R-group size, since the R group would sterically force a better FL angle when larger. DOI: 10.1021/ja00243a042

I think both make the issue clear and unambiguous. If there's something elementary missing from my summary, please notify. --vuo (talk) 08:05, 17 June 2012 (UTC)

Sorry but I have to say that the edits on BD and FL articles have not been improvements. Namely, the current revision doesn't mention diastereoselectivity, even though the main evidence - and indeed motivation - for the research into these angles has been exactly that. I am fully aware of the theoretical, computational, and experimental difficulties associated with reaction mechanism studies. This does not mean that rather simple observations, like the stereoselectivities of attack onto carbonyl compounds with moieties differing by size, could not be presented to illustrate the principle. Moreover, even science articles should be of the style and register suitable for the general interest or undergraduate level, not that of a physical chemistry review article. The current revision is pondering, uses scare quotes, and uses too long, convoluted and confusing sentences. (Exempli gratia: "These angles are generally best construed to mean the angle observed/measured for a given system, and not an historically observed value range (e.g., as the BD angle and the original Bürgi–Dunitz aminoketones), or an idealized value computed for a particular system (such as the 0° for hydride addition to formaldehyde, image at right). I.e., the BD and FL angles of the hydride-formadehyde system have one pair of values, while the angles observed for other systems are expected to vary.") Furthermore, the article suffers from the wall-of-text phenomenon: it is essentially a very long lede/introduction that deters casual reading, makes cursory reading difficult and doesn't come to a definite conclusion. The best way to reorganize it would be to present a condensed definition, an ideal example, each of the different pieces of evidence and their merits, and each of the chemical nonidealities separately, each in a separate section. --vuo (talk) 20:55, 5 September 2012 (UTC)

vuo, Great summary of points from the Flippin and Lodge papers, more on this in following. Also agree fully (a) that restructuring of the text into sections is long overdue, and that (b) the first draft text could be turned into shorter and more active prose. I would also add that the FL angle image is at best preliminary, and (as one who has had his students determine these from crystallographic data), the image requires the long and convoluted legend to make clear how the angle measurements are actually derived in relation to the image. "Picture is worth a thousand words." Lacking a better picture, we are left with the many words of the legend.

Note as introduction the goals of writing this FL and the related BD "stub" were, (i) to get it done, with important references, (ii) to make the relationship/complementarity between the BD and FL angles clear; (iii) to make clear that the BD angle is not 107 deg any more than the FL is 0 deg (hydride-HCHO calc'd values), but that, rather, it is a characteristic of each reactive experimental system, with more or less clustering/convergence about particular values, see next goal; (iv) to make fully clear from the literature how the VdW/steric and orbital influences of nucleophile and electrophile are distinctly different in determining the observed BD anf FL values, (v) to begin to make clear the breadth of the applicability of the two angles (including, in the FL case, diastereoslectivity, but not limited to that separate, and poorly developed Wikipedia concept, see below), and (vi) to make first mention of BD and FL in relation to biochemical systems, which were first brought in by B-D but never by F-L-H, where the concept clearly applies but is either generally misused (BD) or is wholly ignored (FL).

This said, your aims are accepted, encouraged, and I hope will be achieved in time. The Stub accomplishes only what its goals were, and then imperfectly.

Next, while I take issue with your contention that the main evidence and motivation for the BD come from studies of diastereoselectivity, what you say is clearly true for the FL angle. But just as critical (in my view): Do you not perceive that the FL angle is under-appreciated? That it is only appreciated with respect to the development of new diasteroselective reactions, though it has been equally important (though a silent partner) in nearly every experimental case where the the BD has been described and discussed down the years, though the FL received nary a mention? Part of the point of the FL and BD articles is to step back from any one application or use of either angle, to show their comparable conceptual basis, the differences in the structural contributions determining each of their values, and (only) then to note ways in which the two angles can be applied. (It is this last goal you address, and it can certainly use further beefing up.)

Otherwise, how might you further generalize your extracts from the Flippin and Lodge papers, in an encyclopedic manner, as Heathcock attempted to do in the Aldrichimica review (since WIkipedia prefers secondary sources, and accessibility to as broad and general an audience as possible)? Perhaps you can edit the three bullet points in the FL article, on the effects of substituents on observed FL angle values (derived from these same two papers)? In considering this, though your extracts are, even as they stand, completely valid and on point to a researcher in these areas—please note, references to R2-enolates, α-methyl-R1-aldehydes, t-butyl acetate-derived TBDMS enolates, etc. are bound to throw people. Even something as simple (to an advanced UG/G OChem student) as your original reference to syn/anti selectivity must be clearly laid out, with images, somewhere in the encyclopedia, in order for it to appear here in summary form in this article. Bottom line, professionals and specialists will likely understand regardless of how you you extract and summarize; but this is not the audience for whom we are writing.

Finally, the current FL article does mention diastereoselectivity (and the BD mentions it indirectly through citation)—the problem being that there is currently no Wikipedia article on this important synthetic organic subject. Are you interested in creating some text here (you can place it here in Talk, and we and others can assist with the Wiki end of things), or would you be interested in submitting a diastereoselectivity stub yourself? I would start with Carey and Sundberg / Lowry and Richardson / March level of definition with a simple example, to suffice as the first pass stub—don't even try to tackle all of the content of Evans, Boger, etc. lecture notes, and certainly not Flippin and Lodge, etc. (Before beginning, search diastereoselectivity at Wikipedia, and you will see it making appearances at Stereoselectivity and Diastereomer, and you will see a couple of mildly applicable figures; then search Felkin-Ahn and any other models that already appear in Wikipedia, but be prepared for possible gnashing of teeth.)

After creating your stub, in the talk section of that new article, you could generate a first broad outline including all of the detail, which you and other interested parties could flesh out, with high quality, over time. I strongly encourage you to consider this—you clearly have the interest and background. Even a stub with a decent definition of the term, and a decent scheme with an example, would be a major contribution to Wikipedia organic chemistry content. (My firm opinion.)

Bottom line, without a place to go for clear definition (with appropriate history and images), dropping standard advanced OChem terms repeatedly does no more than introduce jargon that reader cannot hope to understand. (And if I could not easily follow your initial prose, knowing the literature and what you meant, how could my students?) As well, focusing on any one area does not further the goal to have the reader appreciate that this angle applies everywhere that a nucleophile is approaching a trigonal electrophilic center, even if this aspect of trajectory (approach geometry) has yet to be fully described. North and South America were discovered by a few specific transoceanic explorers, but the meaning and importance of these as subjects are much broader than the context of their initial description/discovery. The focus, to date, of these stubs has not been on the very important and successful applications of either BD or FL understanding (such as diastereoselectvity, which deserves full article attention), the application paragraph/subsection of the article can clearly be improved. Meanwhile, I hope that we have covered the geometric and VdW/steric and orbital overlap principles underlying the influence of FL on diastereoselectivity. In short, I agree fully with your leaning, agree with the importance of the topic you suggest, but ask, how can we get the basics of diastereoseletivity into Wikipedia, and then further develop them as examples here? Cheers. LeProf — Preceding unsigned comment added by 50.179.92.36 (talk) 07:29, 26 November 2013 (UTC)

Work on lede and on sectioning body

I wrote an approachable lead for the article, sectioned the body (a first pass). PLease reply here with any comments and suggestions. Same will occur shortly at the Burgi-Dunitz article, so commenting here soon will help a lot. Thanks. Le Prof — Preceding unsigned comment added by 12.40.94.210 (talk) 22:47, 11 December 2013 (UTC)

General improvements begun. Please expand applications with good text, figures

I began the improvements called for above. The article still focuses on concepts, and the relationship of FL to BD. So, Heatchcock's diastereoselection work is referenced, but it and any later work citing the FL is still under-represented in the text. (And, no aldol figures!) Someone with background in aldol reactions can improve it. Can someone add applications, and especially provide examples consistent with the summary in the "Steric and orbital contributions..." section? Thank you. — Preceding unsigned comment added by 12.40.94.210 (talk) 23:48, 11 December 2013 (UTC)

Started condensing the figure legend.

But will stay a little long. We need a figure that shows the projection of Nu to the >C=O plane (illustrating Nu', etc.). — Preceding unsigned comment added by 12.40.94.210 (talk) 23:56, 11 December 2013 (UTC)

Image temporarily made larger.

This makes the legend mode readable--not a long column. — Preceding unsigned comment added by 12.40.94.210 (talk) 23:59, 11 December 2013 (UTC)

Need for edit buttons on each section...

...can someone do this? LeProf — Preceding unsigned comment added by 50.179.245.225 (talk) 04:21, 6 January 2014 (UTC)

I laugh when I look back at this, understanding now that they automatically appear. Cheers. Le Prof Leprof 7272 (talk) 21:28, 27 May 2014 (UTC)

Tidying work on added text

Some text was added to the Applications that tried to simplify and generalize the meaning in nucelophilic attack at aldehydes and ketones. The problem was the looseness of the language, and I tried to address this. Note, in general, few have attempted to measure FL angles (though my group has, and I am encouraging others to as well). Unlike the BD angle, FL angles are inferred, based on reaction outcomes, or are computed based on theoretical studies. This means one has to be careful how the description of these studies is presented. You can't imply that a parameter was measured when it really was not; when we infer mechanisms from ratios of diastereomers, we are doing just that—inferring what must be happening in something we cannot see (the approach of the nucelophile to the electrophile in solution) via something we can see (carefully derived quantities of products whose structures we have determined with confidence). We both need to appreciate the difference between FL experiments and the early BD approach, and we have to try to get it across to lay readers. Le Prof Leprof 7272 (talk) 21:27, 27 May 2014 (UTC)

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