Synthetic Studies on the MARDi Cascade: Stereoselective Synthesis of Heterocyclic Seven-Membered Rings

Abstract

[reaction: see text] A versatile stereoselective synthesis of substituted and functionalized heterocyclic seven-membered rings is described. The approach involves a formal two-carbon ring expansion of heterocyclic cyclopentanones through a base-induced anionic domino three-component transformation named the MARDi cascade leading either to oxa-, aza-, or thiacycloheptanes bearing up to five contiguous stereogenic centers.

Eight‐Membered‐Ring Lactams – New Scaffolds for Combinatorial Chemistry Prepared by Ring‐Expansion of 1,4‐Diketones with Primary Amines

“…A subsequent retro-Claisen reaction cleaves the central bond (between C-1 and C-5) of bicyclic 7 and forms a monocyclic eight-membered-ring product 4. Similar retroClaisen reactions of bicyclic intermediates were recently reported for the formation of heterocyclic seven-membered rings [12] (Scheme 3).…”

The MARDi Cascade: A Michael‐Initiated Domino‐Multicomponent Approach for the Stereoselective Synthesis of Seven‐Membered Rings

“…[29] From our previous results, we surmised that the MARDi cascade could allow a quick access to a variety of heterocyclic sevenmembered rings. [30] The hetero-MARDi cascade was first tested (see structures depicted below) in the oxygen series with furanone 17 a, obtained from methyl glycolate and methyl acrylate, [31] and the isomeric furanones 17 b-g, formed by rhodium-carbenoid insertion into the OH bond of the corresponding dhydroxy-b-ketoesters [32] or d-hydroxy-b-ketosulfone [33] . The study was initiated with furanone 17 a and the representative aldehydes 2 a,b and 2 g, which were allowed to react under the previously optimised conditions.…”

“…The experimental protocol and the characterization data for the heterocyclic seven-membered rings 21 a-e, 25 a-e, 26 a-d and 26 f have been reported previously (see reference [30]). The structures of compounds 13, 14, 20, 22 and 23 were determined by 13 C NMR and mass spectroscopy of the crude material and the products were not further characterised.…”

“…Thiepine trans-26 e: This compound has been prepared by treatment of the corresponding carboxylic acid 26 d with TMSCHN 2 as described in reference [30]. …”

1,3-Dicarbonyl compounds in stereoselective domino and multicomponent reactions

“…The MARDi cascade is very general and can also be realized starting from β-ketosulfones with complementary diastereoselectivity and reactivity 75 or in the heterocyclic series (Figure 3). 76 The reaction allows the control of up to five newly created stereocenters, and a complete chiral induction in the case an optically active β-ketoester precursor. An application of the MARDi cascade to the synthesis of the tricyclic ring system of guaianolide natural products was reported recently.…”