Combined Transition‐Metal‐ and Organocatalysis: An Atom Economic C3 Homologation of Alkenes to Carbonyl and Carboxylic Compounds

Abstract

A combination of regioselective room-temperature/ambient-pressure hydroformylation (transition-metal catalysis) and decarboxylative Knoevenagel reactions (organocatalysis) allowed for the development of an efficient, one-pot C3 homologation of terminal alkenes to (E)-alpha,beta-unsaturated acids and esters, (E)-beta,gamma-unsaturated acids, (E)-alpha-cyano acrylic acids, and alpha,beta-unsaturated nitriles. All reactions proceed under mild conditions, tolerate a variety of functional groups, and furnish unsaturated carbonyl compounds in good yields and with excellent regio- and stereocontrol. Further, an iterative C2 homologation of (E)-alpha,beta-unsaturated carboxylic acids is possible through a combination of decarboxylative hydroformylation employing a supramolecular catalyst followed by decarboxylative Knoevenagel condensation with an organocatalyst.

Crystal structure of (E)-undec-2-enoic acid

“…For an adapted direct synthesis of the title compound following the procedure established by Knoevenagel (1898) and Doebner (1902), see: Bikulova et al (1988); Kemme et al (2010). For crystal structure determinations of related unsaturated ,-carboxylic acids, see, for acrylic acid: Higgs & Sass (1963); Chatani et al (1963); Boese et al (1999); Oswald & Urquhart (2011); see, for crotonic acid: Shimizu et al (1974); see, for (E)-pent-2-enoic acid: Peppel et al (2015a); see, for (E)-hex-2-enoic acid: Peppel et al (2015b).…”

Domino Reactions Triggered by Hydroformylation

“…More recently, Breit and coworkers [67] use a developed room temperature/ambient pressure HF methodology as the first step in a decarboxylative organocatalyzed Knovenagel reaction, producing an efficient one-pot C3 homologation of terminal alkenes to (E)-α,β-unsaturated acids 129, esters 131, and nitriles 133, (E)-β,γ-unsaturated acids 130, and (E)-α-cyano acrylic acids 132. Inspired from the fattyacid biosynthesis an iterative two-carbon homologation of the (E)-α,β-unsaturated acid 134 is possible using a supramolecular catalytic system (Scheme 29).…”

Combinations of Aminocatalysts and Metal Catalysts: A Powerful Cooperative Approach in Selective Organic Synthesis

“…In 2010, Breit and co-workers demonstrated a one-pot combination of a transition-metal-catalyzed hydroformylation with an aminocatalyzed Knoevenagel reaction. 327 Later on, the group of Christmann and Behr presented a similar strategy for the one-pot hydroformylation and S N 1 alkylation. 328 The The group of Jang demonstrated the formation of β-azido-αoxyaminated aldehydes through a tandem process that was catalyzed by a combination of FeCl 3 •6H 2 O and an aminocatalyst.…”