Corrigendum: Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial‐F Preference

The authors became aware that the values of free enthalpy differences (ΔG) and dipole moments (μ) of some compounds (1A, 3A, 4A, 5C, 9A, 11A, 12A, 13, 14, 15) given in the main manuscript were reported incorrectly. Although the mentioned values are presented correctly in the Supporting Information, the corrected Schemes (Scheme 2 and 3) and Tables (Table 1 and 2) are shown below to avoid any future confusion. This correction does not alter in any way the analysis and conclusions drawn in the article. The authors apologize for this error and for any inconvenience caused.

Scheme 1.

The conformational preferences of 3‐fluoropiperidine (1) and 3,5‐difluoropiperidine (2) and their TFA‐(A), HCl‐(B), and NH‐(C)‐analogues. The free enthalpy differences between the equatorial conformer to the axial conformer (ΔG) are presented as follows: ΔG Solvent (ΔG Gas Phase). The ΔG values for TFA‐, and for both HCl‐, and NH‐analogues are given in chloroform and water, respectively. All values are given in kcal mol⁻¹. Experimentally, all analogues of 1 and 2 showed high axial preference. In NH‐analogues 1C and 2C, we were unable to determine the orientation of the N−H bond because of a fast H/D exchange in solution. [a] Both computational analysis and experimental observation were carried out in toluene.

Scheme 2.

The conformational preferences of cis‐3‐fluoro‐4‐methylpiperidine (3) and its TFA‐(A), HCl‐(B), and NH‐(C)‐ analogues. All values are given in kcal mol⁻¹. The experimental observation is based on ³ J(¹⁹F,¹H) values. See the Supporting Information for more details.

Table 1.

Conformational behavior of all‐cis‐(multi)fluorinated piperidines.^[a]

	$\Delta G^{298}(a\to e)$ [kcal mol−1]
Compd.	Gas phase	H2O	CHCl3	Exptl.
1, A	−0.4	–	+ 0.1[b]	axial
B	+4.8	+1.8	–	axial
C	0.0	+0.1	–	axial
2, A	−1.4	–	+0.9	axial
B	+8.6	+3.9	–	axial
C	−0.3	+0.8	–	axial
3, A	+1.8	–	+2.3	axial
B	+6.2	+3.6	–	axial
C	+2.1	+2.2	–	axial
4, A	−1.7	–	−1.2	equatorial
B	+2.9	−0.4	–	equatorial
C	−1.9	−2.0	–	equatorial
5, A	−4.3	–	−3.7	equatorial
B	+6.2	+3.3	–	axial
C	+2.0	+2.1	–	axial
6, A	−3.7	–	−3.3	equatorial
B	+6.8	+3.5	–	axial
C	+2.5	+2.7	–	axial
7, A	−6.0	–	−4.4	equatorial
B	+7.7	+5.2	–	axial
C	+1.3	+2.1	–	axial
8, A	+0.2	–	+0.6	axial
B	+4.2	+1.1	–	axial
C	+0.4	+0.3	–	axial
9, A	+0.1	–	+2.2	axial
B	+9.5	+5.1	–	axial
C	+1.7	+2.8	–	axial
10, A	+0.7	–	+0.4	axial
B	+3.0	+1.0	–	equatorial
C	−0.9	−0.4	–	equatorial
11, A	+1.8	–	+1.7	axial
B	+3.9	+2.3	–	axial
C	+0.5	+1.1	–	axial
12, A	+3.7	–	+3.6	axial
B	+0.4	−1.7	–	equatorial
C	−3.7	−3.7	–	equatorial

[a] The conformational preferences of fluorinated piperidine (1–12) and its R=TFA‐(A), HCl‐(B), and NH‐(C)‐analogues. The ΔG values for TFA‐ and for both HCl‐, and NH‐analogues are given in chloroform and water, respectively. All values are given in kcal mol⁻¹. [b] This compound was measured in toluene.

Table 2.

The conformational preferences of 3,5‐difluoropiperidine derivatives.^[a]

Compd.	Solvent	$\Delta G^{298}(a\to e)$ [Kcal mol−1]	μ (a)	μ (e)	Exptl.
R=TFA (2A)	none	−1.4	6.6	2.2	–
	C6H6	+0.1	8.1	2.7	axial
	CHCl3	+0.9	8.9	3.0	axial
	CH2Cl2	+1.4	9.3	3.2	axial
	DMSO	+2.0	9.8	3.3	axial
R=AC (13)	none	−1.6	5.8	2.8	–
	CHCl3	+0.4	8.1	3.8	axial
	DMSO	+1.1	8.9	4.2	axial
R=Piv (14)	none	−2.3	5.2	2.8	–
	CHCl3	−1.0	7.6	3.8	equatorial
	DMSO	+0.5	8.4	4.2	axial
R=Boc (15)	none	−2.4	4.2	2.4	–
	CHCl3	−1.0	5.9	3.1	equatorial
	DMSO	+0.7	6.5	3.3	axial

[a] All values are given in kcal mol⁻¹. The experimental observation is based on ³ J(¹⁹F,¹H) values. See the Supporting Information for more details.