1. Stereoinversion of tertiary alcohols to tertiary
alkyl isonitriles and amines
Sergey V. Pronin, Christopher A. Reiher, Ryan A. Shenvi
The Scripps Research Institute, La Jolla, California.
Nature 501, 2013, 195–199.

2. Ryan A. Shenvi
B.S in chemistry at Penn State with Prof. Raymond L. Funk
Ph.D. from The Scripps research Institute with Prof. Phil S. Baran
Postdoctoral fellowship in Harvard University with Prof. Elias J. Corey
Assistant Professor ( ),
Department of Chemistry,
The Scripps Research Institute.
Research Interests: Total synthesis of terpenes, Alkaloids and natural
products targeting neglected tropical diseases

3. Isonitrile containing secondary terpenoid metabolites

4. Common methods to access isonitriles

5. tert-Isonitrile synthesis in Natural products

6. A direct conversion of alcohols to isonitriles
Kitano, Y.; Kazuhiro, C. Tada, M.; Tet. Lett ,

7. Lewis acid modification

8. Lewis acid screening

9. Lewis acid modification

10. Substrate Scope

11. Substrate Scope

12. Transformations of formed isonitriles

13. Limitations

14. Mechanistic rationale

15. Increase in fluorination of the substrate ester has an effect on the selectivity
towards inversion
Use of TMSOTf instead of Sc(OTf)3 did promote any reaction.
Addition of 2-6-di-t-butyl pyridine (3:1 with catalyst) did not inhibit product formation,
which excludes Bronsted acid catalysis.
Addition of stoichiometic TMSOTf did not affect the reaction
Reaction seems to be unique to TMSCN as nucleophile/solvent No reaction when MeCN
is used as nucleophile, TMSN3 and TMSSCN gave complex mixtures

16. Conclusions
The methodology can be used for
Stereoslective conversion of 3 o alcohols to isonitriles and amines
Is chemoselective to 3 o alcohols in the presence of 1 o and 2 o alcohols
Works best with minmally branched acylic alcohols and conformationally
inflexible alicyclic alcohols

17. Other examples from literature for SN2 at tert-center