Chiral Benzylic Carbocations: Low-Temperature NMR Studies and Theoretical Calculations

Abstract

The alpha-chiral secondary and tertiary benzylic carbocations 19-30 were generated from the corresponding benzylic alcohols 1, 2, and 5-14 by treatment with FSO(3)H or FSO(3)H/SbF(5) in SO(2)ClF as the solvent at -70 degrees C and characterized by one- and two-dimensional NMR spectroscopy. Coupling constants and NOESY measurements suggest a preferred conformation in which the alpha-hydrogen atom occupies the 1,3-allylic-strain position and the diastereotopic faces of the cations are differentiated by the alkyl substituent and a functional group (FG). The existence of this preferred conformation is further supported by calculations using a DFT method at the B3LYP/6-311+G** level. Quenching experiments with an arene nucleophile showed a preferential attack from the less shielded diastereotopic face delivering high diastereomeric ratios, supporting the hypothesis that these carbocations are involved as intermediates in previously studied S(N)1 reactions. A strong shielding effect at the benzylic carbocationic center is observed for most of the secondary benzylic carbocations (derived from precursors 5-13) investigated, indicating a strong mesomeric distribution of the positive charge to the carbon atom in the para-position of the anisyl substituent. For alpha-halogen-substituted carbocations (5-7, 12), no neighboring halogen participation leading to halonium ion formation was observed.

Monitoring Mechanistic Details in the Synthesis of Pyrimidines via Real-Time, Ultrafast Multidimensional NMR Spectroscopy

“…A mechanism capable of rationalizing all the observed peaks is depicted in Figure 8. The HSQC series recorded on the 1.54 - 2.87 ppm, 1 H; 23.7 - 33.7 ppm, 13 C aliphatic window, indicate that the reaction starts with an electrophilic attack of the S-atom of one of the SO 2 groups of triflic anhydride on the O-atom of the carbonyl group of acetophenone ( 7 ) leading to the rapid formation of an intermediate ( 8 ), whose presence we have detected in the past by ultrafast 2D HMBC experiments,13c,19 but whose cross-peaks fall outside the window targeted here. Evolution of ( 8 ) by nucleophilic capture by acetonitrile- d 3 leads to the complex ( 11 ), which evolve to the nitrilium-salt intermediate ( 12 ) 20,21.…”

Computational NMR of charged systems

“…The carbocationic center of 71 was found to be strongly deshielded (275.9 ppm), in analogy with the T A B L E 1 1 13 C NMR chemical shifts of 2-(trifluoromethyl)cyclopentyl carbocation (61), isomeric primary nonclassical structures 62, 63, and 66, cyclobutyl (difluoromethyl)methyl cation (64), and cyclobutyl (fluoromethyl)methyl cation (65) Note: Compiled from Reddy et al [60] related static tertiary carbocations, the former being substantially trivalent (i.e., "classical") in nature, with the expected charge delocalization into the cyclopropyl rings. The classical nature of the carbocation 71 was also confirmed by its experimental 13 C NMR chemical shifts demonstrating that the carbocation existed in solution mainly as the Cs symmetric bisected conformer.…”

“…The structures and salient bond lengths (in Angstroms) of 2-(trifluoromethyl)cyclopentyl carbocation (61), isomeric primary nonclassical structures 62, 63, and 66, cyclobutyl (difluoromethyl)methyl cation (64), and cyclobutyl (fluoromethyl)methyl cation (65), optimized at the MP2/cc-pVTZ level. Reproduced with minor editing privilege from Reddy et al [60] under the Creative Commons Attribution 4.0 International Public License…”

“…A number of more complex, structurally diverse carbocations were generated in superacidic media at low temperatures and studied by means of the high-level quantum chemical calculations in Olah's group, which is exemplified by chiral benzylic carbocations, [64] chiral propargylic cations, [65] and long-lived (pentafluorosulfanyl)phenyl-substituted carbocations. [66] For more details, readers are kindly forwarded to the original publications given above.…”

Silylium‐Catalyzed Carbon–Carbon Coupling of Alkynylsilanes with (2‐Bromo‐1‐methoxyethyl)arenes: Alternative Approaches

“…Next, the benzylic nature of the leaving group would favor the formation of the reactive carbocation II. [13] Scheme 2. Hypothesis behind the proposed alkynylation without bromine lost.…”