Can acyclic conformational control be achieved via a sulfur-fluorine gauche effect?

C Thiehoff; M C Holland; C Daniliuc; K N Houk; R Gilmour

doi:10.1039/c5sc00871a

Can acyclic conformational control be achieved via a sulfur-fluorine gauche effect?

Chem Sci. 2015 Jun 1;6(6):3565-3571. doi: 10.1039/c5sc00871a. Epub 2015 Apr 17.

Authors

C Thiehoff¹, M C Holland^{1

2}, C Daniliuc¹, K N Houk², R Gilmour^{1

3}

Affiliations

¹ Organisch Chemisches Institut, and Excellence Cluster EXC 1003 , Cells in Motion , Westfälische Wilhelms-Universität Münster , Corrensstrasse 40 , Münster , Germany . Email: ryan.gilmour@uni-muenster.de.
² Department of Chemistry and Biochemistry , University of California Los Angeles , 607 Charles E. Young Drive East , Los Angeles 90095-1569 , USA . Email: houk@chem.ucla.edu.
³ Excellence Cluster EXC 1003 , Cells in Motion , Westfälische Wilhelms-Universität Münster , Münster , Germany.

Abstract

The gauche conformation of the 1,2-difluoroethane motif is known to involve stabilising hyperconjugative interactions between donor (bonding, σ_C-H) and acceptor (antibonding, σ*C-F) orbitals. This model rationalises the generic conformational preference of F-C_β-C_α-X systems (φ_FCCX ≈ 60°), where X is an electron deficient substituent containing a Period 2 atom. Little is known about the corresponding Period 3 systems, such as sulfur and phosphorus, where multiple oxidation states are possible. Conformational analyses of β-fluorosulfides, -sulfoxides and -sulfones are disclosed here, thus extending the scope of the fluorine gauche effect to the 3rd Period (F-C-C-S(O) _n ; φ_FCCS ≈ 60°). Synergy between experiment and computation has revealed that the gauche effect is only pronounced in structures bearing an electropositive vicinal sulfur atom (S⁺-O^-, SO₂).