Multicomponent Cycloadditions:  The Four-Component [5+1+2+1] Cycloaddition of Vinylcyclopropanes, Alkynes, and CO

Abstract

Prompted by the view that intermediates of transition metal-catalyzed reactions could be intercepted by one or more additional components, studies in our laboratory have led to the design and development of new three-component [5+2+1], [4+2+1], and [2+2+1] cycloadditions. These continuing studies have now led to the identification of a fundamentally new four-component [5+1+2+1] cycloaddition reaction of vinylcyclopropanes, alkynes and CO, yielding hydroxyindanone products in generally good yields. Terminal alkynes bearing aryl or alkyl groups are tolerated well. Substitution at any position of the VCP leads predictably to substituted hydroxyindanone products. Using a bis-alkynyl substrate, the reaction can be carried out bi-directionally, forming 10 C-C bonds and four new rings from seven components in a single, operationally simple process.

Transition metals in organic synthesis: Highlights for the year 2005

“…Rhodium catalyzed a four-component cyclization of a alkenylcyclopropane, an alkyne and two carbon monoxides (Eq. (306)) [1403]. Rhodium catalyzed an enantioselective reductive cyclization of 1,6-enynes (Eq.…”

Iridium Catalyzed Carbocyclizations: Efficient (5+2) Cycloadditions of Vinylcyclopropanes and Alkynes

“…Formation of seven-membered carbocycles from vinylcyclopropanes (VCPs) and alkynes catalyzed by rhodium serves as an illustration. First reported by Wender in 1995, [1] this process has enabled streamlining complex molecule syntheses [2] and provided a mechanistic basis for developing new reactions including higher order cycloadditions [3] and (5 + 2) reactions with other 2p components.[4] Intramolecular versions catalyzed by ruthenium, [5] nickel, [6] and iron [7] have been reported, but the intermolecular reaction that benefits from simple and often commercially available substrates has remained exclusive to rhodium catalysis.[8] A remaining challenge towards improving the efficiency and cost, as well as providing new mechanistic opportunities for interception of intermediates, is the introduction of third-row transition metals as catalysts in this context. [9] To this end, we envisioned that comparatively inexpensive iridium would be a suitable candidate.…”

Use of β,γ‐Unsaturated α‐Ketocarbonyls for a Totally Regioselective Oxidative Multicomponent Synthesis of Polyfunctionalized Pyridines

“…[13] Recently, we reported a metal-free Michael addition initiated three-component substrate directed route to polysubstituted pyridines 4 from 1,3-dicarbonyls 1 that could solve part of the selectivity substitution problem (Scheme 1). [14] This simple and totally regioselective multicomponent reaction (MCR) combines molecular complexity and diversity [15] with economic [16] and environmental aspects. [17] However, this methodology was limited to the use of b-unsubstituted aldehydes and ketones 2 (R 3 , R 4 = H, alkyl), probably because of the reversibility of the Michael addition with hindered substrates; this prevents any access to 4-substituted pyridines and limits the functional diversity at the strategic 2-position.…”