Chiral Propargylic Cations as Intermediates in S_N1-Type Reactions: Substitution Pattern, Nuclear Magnetic Resonance Studies, and Origin of the Diastereoselectivity

Abstract

Nine propargylic acetates, bearing a stereogenic center (-C*HXR(2)) adjacent to the electrophilic carbon atom, were prepared and subjected to SN1-type substitution reactions with various silyl nucleophiles employing bismuth trifluoromethanesulfonate [Bi(OTf)3] as the Lewis acid. The diastereoselectivity of the reactions was high when the alkyl group R(2) was tertiary (tert-butyl), irrespective of the substituent X. Products were formed consistently with a diastereomeric ratio larger than 95:5 in favor of the anti-diastereoisomer. If the alkyl substitutent R(2) was secondary, the diastereoselectivity decreased to 80:20. The reaction was shown to proceed stereoconvergently, and the relative product configuration was elucidated. The reaction outcome is explained by invoking a chiral propargylic cation as an intermediate, which is preferentially attacked by the nucleophile from one of its two diastereotopic faces. Density functional theory (DFT) calculations suggest a preferred conformation in which the group R(2) is almost perpendicular to the plane defined by the three substituents at the cationic center, with the nucleophile approaching the electrophilic center opposite to R(2). Transition states calculated for the reaction of allyltrimethylsilane with two representative cations support this hypothesis. Tertiary propargylic cations with a stereogenic center (-C*HXR(2)) in the α position were generated by ionization of the respective alcohol precursors with FSO3H in SO2ClF at -80 °C. Nuclear magnetic resonance (NMR) spectra were obtained for five cations, and the chemical shifts could be unambiguously assigned. The preferred conformation of the cations as extracted from nuclear Overhauser experiments is in line with the preferred conformation responsible for the reaction of the secondary propargylic cations.

Effect of conformational rigidity on the stereoselectivity of nucleophilic additions to five-membered ring bicyclic oxocarbenium ion intermediates

“…Representations of the transition structures for inside and outside attack are shown in Scheme 5; three-dimensional representations of these structures are provided as supporting information. Critical parameters, such as the length of the developing carbon–carbon bond (ranging between 2.4 and 2.5 Å), agree with values obtained from transition structures identified for allylation of propargylic cations 53 . The carbon–silicon bond is anti-periplanar to the developing carbon–carbon bond, which would be expected because of stabilization of the incipient carbocationic center by the carbon–silicon σ-bond 54,55 .…”

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.…”

Catalytic Oxidation of Primary C–H Bonds in Alkanes with Bioinspired Catalysts

“…[46,47,50,[57][58][59][60][61][62][63][64][65][66] Products 2a and 2b were prepared according to literature protocols. [67][68][69][70]…”