One-pot synthesis of tropinone by tandem (domino) ene-type reactions of acetone silyl enol ethers

Abstract

A synthetic approach for tropane alkaloids on the basis of tandem (domino) ene-type reactions of acetone silyl enol ethers with iminium ions is shown to be triggered by intermolecular ene-type reactions followed by 6-(2,5) silatropic ene-type cyclizations.

Biomimetic Synthesis of Ornithine/Arginine and Lysine‐Derived Alkaloids: Selected Examples

“…Questions interfacing biosynthesis and chemistry arose continuously concerning tropane alkaloids; they were compiled and analyzed by O'Hagan and Humphrey in a review article [67]. The use of siloxy(allyl)silane was also reported in place of acetonedicarboxylates (avoiding thereby the double thermal decarboxylation step) and afforded tropinone in good yield [69]. By way of an example, a solid-phase version was developed as an interesting means of generating tropane analogs in a combinatorial way [68].…”

Trimethylsilyl Trifluoromethanesulfonate

“…114 The tropane alkaloid skeleton can be accessed in one pot via domino ene-type reactions of acetone silyl enol ether, the first one of them being intermolecular, with catalytic use of TMSOTf (eq 79). 116 Alternatively, asymmetric tropinones can be reached by cyclization of 1,3-bis-silyl enol ethers with acyliminium triflates. 117 TMSOTf is effective in both stoichiometric and catalytic modes to promote the [4 + 3] cycloaddition of dienes to 1,1-dimethoxyacetone-derived silyl enol ethers (eq 80).…”

“…Other Lewis acids such as germanium(IV) chloride proved to be even more efficient for such transformation. (116) The generation of thionium ions from sulfoxides bearing an α-hydrogen can be carried out by using TMSOTf-Et 3 N as initiator to afford Pummerer reaction products (eq 117 (117) Several coupling reactions have been activated by the addition of TMSOTf.…”

Formal (3+3) Cycloaddition of Silyl Enol Ethers Catalyzed by Trifric Imide: Domino Michael Addition-Claisen Condensation Accompanied with Isomerization of Silyl Enol Ethers

“…To the best of our knowledge, only limited studies of domino reactions consisting of two bondformation reactions based on the concept have been reported. [7][8][9][10] We have reported on a catalytic (2ϩ2) cycloaddition, in which silyl enol ethers 1 react with a,b-unsaturated esters 2 in the presence of triflic imide (Tf 2 NH) at Ϫ78°C giving siloxycyclobutanes 4. [11][12][13][14] In the process, the siloxonium intermediate 3 bearing a ketene silyl acetal moiety, which is formed as a transient intermediate by Mukaiyama-Michael addition, would undergo successive intramolecular aldol reaction (nucleophilic attack) at low temperatures to form a 4-membered ring (Fig.…”

“…Clovane and its related natural products possessing the tricyclo-[6.3.1.0 4,8 ]dodecane skeleton are widely found in essential oil extracted from the fresh leaves of Chamaecyparis. 22,23) We envisaged that the core skeleton would be constructed by the intramolecular (3ϩ3) cycloaddition.…”