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Consider the two molecules below.

enter image description here

A chemical drawing software that I won't name says that the one on the left is chiral with configuration R at sulphur, whereas the one on the right isn't.

I checked this with the software developers, and their answer was "Sulfur atoms with three single bonds are not perceived as having stable tetrahedral stereo".

I suspect what they actually meant was that the molecule on the right could be seen as a sulphur with 4 bonds, like:

enter image description here

which is obviously not possible when O is alkylated.

Still, this topic came up because I found an O-akylated sulphoxide similar to the one above in our corporate database (I cannot disclose the exact molecule for confidentiality reasons).

So, if such a molecule can exist, and its registrars thought it appropriate to use a wedge to mark it as a specific enantiomer, what can I conclude?

Can such a sulphoxide have stable stereochemistry, unlike the software developers claimed, or were the registrars wrong, i.e. there is no possible stereochemistry, and they should have used a plain bond?

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2 Answers 2

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More as illustrated comment on this interesting question, than an answer: at least formally, O-alkylated sulfoxides can be chiral. Marvin (test page) for example assigns to your salt the chemical name of (R)-ethyl(methoxy)methylsulfanium chloride:

enter image description here

where CIP rules assign the non-bonding electron pair of sulfur priority zero (i.e. even lower, than a hydrogen) as the sulfoxide group can be written as below:

enter image description here

(source Wikipedia).

Some sketchers outright notify the user if a sulfoxide (not O-alkylated) is depicted in an ambiguous form, e.g. DataWarrior:

enter image description here

and trade similarly the O-alkylated sulfoxide, too:

enter image description here

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  • $\begingroup$ Thanks! So, as I suspected, the software I am unfortunately having to use is just wrong, as it often is, and the developers are probably just stating their own prejudice or ignorance rather than any fundamental chemical truth. I am just amazed that there should be no evidence in the literature (I looked for it before posting of course) of such compounds. I will have a look in Scifinder maybe. $\endgroup$ Commented Apr 5 at 12:20
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    $\begingroup$ OK Scifinder finds 1029 O-alkylated sulphoxides, 34 of which are supposedly commercial. 51404-81-0 is reported as chiral with 'R' configuration. So are 59710-97-3, 51404-82-1, 134297-13-5, and several more. Either all these people were wrong depicting such compounds with stereo wedges, or O-alkylated sulphoxides can have stereo at the S atom. $\endgroup$ Commented Apr 5 at 12:32
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    $\begingroup$ OK, I understand that people may not 'know' about something, but then when a paying customer reports an inconsistency of their software to them (which BTW causes wrong suppression of stereochemistry in corporate databases), instead of making such claims/statements like the one I reported ('not perceived as having stable tetrahedral stereo'), they should just acknowledge that they are wrong and plan a fix of their software for a future release (and thank the customer). Sorry for the rant, but it has really been a constant attitude from them to always say the customer is wrong. Enough. $\endgroup$ Commented Apr 5 at 12:35
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    $\begingroup$ But before responding in this sense to them, I at least took the step to check with this expert community whether I was actually wrong or not. So thanks for your input and research, it is really appreciated. $\endgroup$ Commented Apr 5 at 12:38
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    $\begingroup$ offers), only a few were lucky enough to have some deeper insight -- not by mere training, but because they were advisors to these projects. But a) these chemists either soon or already are retired, and b) the big players (Elsevier, ACS [equally involved in the digitization of Chemisches Zentralblatt]; to some degree Thieme [Houben-Weyl -> Science of Synthesis) are even less open how the inner of their products are designed and work. And c) today's AI (too often used shot gun like) isn't always easy understood in the old (critically curated) way of if cause A, then result B, either. $\endgroup$
    – Buttonwood
    Commented Apr 5 at 13:45
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There is not a pi interaction that makes the molecule planar (and this actually applies to both molecules, with and without the alkylation on the oxygen). Rather, because one of the "substituents" attached to the apparent stereocenter (sulfur) is a nonbonding pair, it can undergo umbrella inversion like the nitrogen atom in a simple amine. Thus while either conformation would be chiral, the observed compound would racemize and lose its chirality in experimental observation.

We can recover the chirality of an individual conformation in either of two ways. One method is to lower the temperature so that the umbrella inversion (which requires some activation energy) is kinetically hindered. The other method is to incorporate the chiral sulfoxide structure into rings that mechanically prevent the inversion.

As an aside: the use of the "R" in the left molecule to indicate orientation at the sulfur (apparently failing to recognize umbrella inversion) is misleading because "R" is standard nomenclature for an alkyl group. The software should have used a distinct font or markings such as parentheses to clarify the meaning.

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  • $\begingroup$ Thanks; I don't understand however what makes the O-alkylated case different from the simple sulphoxide. And I can report that the original molecule I was referring to was indeed cyclic, if that makes any difference. $\endgroup$ Commented Apr 5 at 10:11
  • $\begingroup$ The left molecule appears to have an R group attachrd to sulfur, whivh takes away the lone pair ans stops the inversion. Without tge R group the sulfoxide would again undergo umbrella inversion. $\endgroup$ Commented Apr 5 at 10:34
  • $\begingroup$ No, sorry, that 'R' is just the tag the drawing software puts there to indicate the configuration of the stereocenter. This is just a standard sulphoxide. The question remains for me: can both these molecules form stable stereoisomers? I know sulphoxides do, I just do not know about O-alkylated ones, as I don't recall coming across them before. $\endgroup$ Commented Apr 5 at 10:56
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    $\begingroup$ Sorry, I don't know what 'Sheesh!' means. I can only reiterate the point that standard sulphoxides are known to have fairly stable stereoisomers, as explained here "The energy barrier required to invert this stereocenter is sufficiently high that sulfoxides are optically stable near room temperature. That is, the rate of racemization is slow at room temperature.". And I repeat, the molecule on the right is the one I am in doubt about, and the original one I cannot disclose is cyclic. $\endgroup$ Commented Apr 5 at 12:17
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    $\begingroup$ @OscarLanzi While I agree of chiral sulfoxides can happen, I would disagree that it is as easy (or as rapidly) as for the smaller nitrogen atom if they are not constrained e.g., by rings (like spartein). They are researched for some time (e.g., Guy Solladie et al.), are used in catalysis and occur in nature (examples in this open access ChemRev). $\endgroup$
    – Buttonwood
    Commented Apr 5 at 12:20

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