Hydrogen bonding shuts down tunneling in hydroxycarbenes: a gas-phase study by tandem-mass spectrometry, infrared ion spectroscopy, and theory

Hydroxycarbenes can be generated and structurally characterized in the gas phase by collision-induced decarboxylation of α-keto carboxylic acids, followed by infrared ion spectroscopy. Using this approach, we have shown earlier that quantum-mechanical hydrogen tunneling (QMHT) accounts for the isomerization of a charge-tagged phenylhydroxycarbene to the corresponding aldehyde in the gas phase and above room temperature. Herein, we report the results of our current study on aliphatic trialkylammonio-tagged systems. Quite unexpectedly, the flexible 3-(trimethylammonio)propylhydroxycarbene turned out to be stable-no H-shift to either aldehyde or enol occurred. As supported by density functional theory calculations, this novel QMHT inhibition is due to intramolecular H-bonding of a mildly acidic α-ammonio C-H bonds to the hydroxyl carbene's C-atom (C:···H-C). To further support this hypothesis, (4-quinuclidinyl)hydroxycarbenes were synthesized, whose rigid structure prevents this intramolecular H-bonding. The latter hydroxycarbenes underwent "regular" QMHT to the aldehyde at rates comparable to, e.g., methylhydroxycarbene studied by Schreiner et al. While QMHT has been shown for a number of biological H-shift processes, its inhibition by H-bonding disclosed here may serve for the stabilization of highly reactive intermediates such as carbenes, even as a mechanism for biasing intrinsic selectivity patterns

Asymmetric synthesis of sultones and sulfonic acid derivatives

A highly efficient diastereo- and enantioselective route to alpha, gamma-substituted gamma-sultones via alpha-allylation of lithiated sulfonates bearing 1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose as a chiral auxiliary has been developed. High asymmetric inductions of the alpha-allylations were achieved along with good to excellent yields. In all cases the diastereomerically pure allylated sulfonates could be obtained by recrystallization (de = 98%). Successive acid-catalyzed cleavage of the chiral auxiliary and subsequent diastereoselective ring closure of the sulfonic acid intermediates were accomplished following a one-pot procedure leading to the title compounds in good to excellent yields and excellent diastereo- and enantiomeric excesses (de, ee = 98%). The ring-opening reactions of these sultones were studied intensively with the purpose to develop an efficient asymmetric route to pharmacologically interesting sulfonic acid derivatives. In total, we have achieved facile and highly efficient enantioselective syntheses of alpha,gamma-substituted gamma-alkoxy, gamma-hydroxy and gamma-amino sulfonates in excellent diastereo- and enantiomeric excesses (de, ee = 98%) in all cases via ring-opening reaction of these gamma-sultones with alcohols, water and sodium azide, respectively as key steps. We have proven that the ring-opening of gamma-sultones proceeded via a SN2 mechanism with inversion of configuration at the attacked gamma-carbon atom. Furthermore, we have gained access to alpha, beta-substituted gamma-hydroxy and gamma-amino sulfonates in moderate yields with excellent diastereo- and enantiomeric excesses from chiral gamma-nitro sulfonates, which were synthesized via an asymmetric Michael addition of chiral lithiated sulfonates to nitroalkenes

St. John's Daily Star, 1916-01-03

The St. John's Daily Star was published daily except Sunday between 17 April 1915 - 23 July 1921