Treatment of the dichloride A under the conditions indicated gives B with retention of configuration, while treatment of dichloride C gives D with inversion of configuration.

enter image description here

I am having difficulty drawing out the inversion ring product to find out if the s lone pair can attack from anti to the $\ce{C-Cl}$ σ* bond on the vertical ring. If it does, then, there is retention of product in the first reaction after the $\ce{N3-}$ attacks.

Can someone please help using diagrams?

  • 1
    $\begingroup$ See also Converso, A.; Burow, K.; Marzinzik, A.; Sharpless, K. B.; Finn, M. G. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane:  A Privileged, Bivalent Scaffold for the Display of Nucleophilic Components. J. Org. Chem. 2001, 66 (12), 4386–4392. (dx.doi.org/10.1021/jo015632y) and Díaz, D. D.; Converso, A.; Sharpless, K. B.; Finn, M. G. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane: Multigram Display of Azide and Cyanide Components on a Versatile Scaffold. Molecules 2006, 11, 212–218. (dx.doi.org/10.3390/11040212); pdf $\endgroup$ – Loong Dec 27 '15 at 15:41
  • $\begingroup$ Is there a typo in compound C? Should those oxygens be there? $\endgroup$ – jerepierre Dec 27 '15 at 15:49
  • $\begingroup$ @jerepierre i thought that too... But i dont think its a typo. $\endgroup$ – justbehappy Dec 27 '15 at 15:54
  • 3
    $\begingroup$ C looks OK, but shouldn't the oxygens also be on D? $\endgroup$ – ron Dec 27 '15 at 18:26
  • 4
    $\begingroup$ A reacts at low T due to NGP. The sulfur lone pair displaces the Cl, that's the first SN2 and you have inversion of configuration at carbon. Then the azide displaces the sulfur, a second SN2 again with inversion. The net result of 2 inversions is retention of configuration at the carbon initially bound to Cl. In C there are no lone pairs on sulfur, no NGP, higher activation energy, higher temperature needed to get the azide to react via an SN2 with inversion of configuration. $\endgroup$ – ron Dec 27 '15 at 23:00

The only difference between substrates A and C is disulfide vs sulfone nature at 9-position. Actually, that is good enough to display this major stereochemical outcome. As explained in Ref.1, the disulfide nature at 9-position of A has an advantage of having two lone pair on sulfur, one of which is proximate enough to attack backwardly on $\ce{C-Cl}$ bond ($\mathrm{S_N2}$ in nature) to give an episulfide ring (see following diagram and the extended comment of ron). The reaction center must have an inversion of configuration since the mechanism is $\mathrm{S_N2}$.

Reaction Mechanism

This episulfide intermediate undergoes ring opening backward attack by the intended nucleophile (e.g.,$\ce{N3-}$) to give the final product under 2nd $\mathrm{S_N2}$ mechanism. This stepwise replacement of chlorine by a nucleophile, the first substitution being considerably faster than the second, was first observed by E. J. Corey and E. Block (Ref.2). The nucleophile of their reaction was methoxy group of methanol (solvolysis). However, although they are the first group to suggest the 1,2-epi-sulfonium ion intermediates in these reactions, it was suggested for the initial dichloro compound A formation, not for the solvolysis by methanol. These types of neighboring group participation (NGP; or anchimeric assistance) have been observed previously for bridging carbon, nitrogen, and boron, all for the bicyclooctane series. In mechanistic point of view, this double inversion process preserves stereochemistry in substitution reactions on 2,6-Dihalosubstituted-9-thiabicyclo[3.3.1]nonanes (Ref.3).

Finally, C cannot follow the fast double inversion process due to the lack of a lone pair on $\ce{S}$ bridge, yet undergoes usual $\mathrm{S_N2}$ transformation (slow because the leaving group is $\ce{Cl}$) under the given conditions.


  1. D. D. Díaz, A. Converso, K. B. Sharpless, M. G. Finn, “2,6-Dichloro-9-thiabicyclo[3.3.1]nonane: Multigram Display of Azide and Cyanide Components on a Versatile Scaffold,” Molecules 2006, 11(4), 212–218 (doi: 10.3390/11040212).
  2. E. J. Corey, E. Block, “New Synthetic Approaches to Symmetrical Sulfur-Bridged Carbocycles,” J. Org. Chem. 1966, 31(6), 1663–1668 (DOI: 10.1021/jo01344a001).
  3. A. Converso, K. Burow, A. Marzinzik, K. B. Sharpless, M. G. Finn, “2,6-Dichloro-9-thiabicyclo[3.3.1]nonane: A Privileged, Bivalent Scaffold for the Display of Nucleophilic Components,” J. Org. Chem. 2001, 66(12), 4386–4392 (DOI: 10.1021/jo015632y).

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.