α-C–H Functionalization of π-Bonds Using Iron Complexes: Catalytic Hydroxyalkylation of Alkynes and Alkenes

Abstract

The discovery of catalytic systems based on earth-abundant transition metals for the functionalization of C–H bonds enables streamlined and sustainable solutions to problems in synthetic organic chemistry. In this Communication, we disclose an iron-based catalytic system for the functionalization of propargylic and allylic C–H bonds. Inexpensive and readily available cyclopenta­dienyliron­(II) dicarbonyl complexes were employed as catalysts for a novel deprotonative activation mode for C–H functionalization, an approach that allows for the direct union of unsaturated building blocks with aryl aldehydes and other carbonyl electrophiles to deliver a range of unsaturated alcohol coupling products under operationally simple and functional group tolerant reaction conditions.

Selective propargylic C(sp3)–H activation of methyl-substituted alkynes versus [2 + 2] cycloaddition at a titanium imido template

“…A precoordination of the alkyne to the titanium center to give an alkyne-titanium π-complex ( X ) is suggested to lower the p K a of the propargylic hydrogen atom(s) in the first place. 19 Even though this type of reactivity is very rare for titanium imido complexes, it was observed for reversible C(sp 3 )–H activation processes in the case of alkanes. 2 b ,20 Just recently, Tonks et al also observed propargylic C–H activation of 3-hexyne by a titanium bisamido complex.…”

Redox-Neutral Propargylic C–H Functionalization by Using Iron Catalysis

“…With a suitable catalyst and an operational catalytic system in hand, we sought to expand the electrophile scope to generate more synthetically applicable products. 46 We were drawn to aldehydes as starting materials due to the ready availability of the functional group and the synthetic versatility of the homopropargylic alcohol products that would result.…”

Gold-catalysed asymmetric net addition of unactivated propargylic C–H bonds to tethered aldehydes

“…The latter process is completely atom economic, avoids the use of stoichiometric metal and/or costly substrates and the generation of stoichiometric metal salt waste, and could be achieved via sequential deprotonation-propargylation-protonation in a catalytic manifold. This type of chemistry constitutes a catalytic asymmetric propargylic C-H functionalization 3 – 11 but to be the best of our knowledge has no literature precedent. In the recently-reported racemic case, 11 aldehyde substrates possessing α-C(sp 3 )-H bonds are not permitted.…”

“…This type of chemistry constitutes a catalytic asymmetric propargylic C-H functionalization 3 – 11 but to be the best of our knowledge has no literature precedent. In the recently-reported racemic case, 11 aldehyde substrates possessing α-C(sp 3 )-H bonds are not permitted. Such substrates are challenging and appear not conceptually feasible under typical basic conditions as the propargylic protons are much less acidic ( p Ka >30) than aldehyde α-hydrogens ( p Ka ~17) in an ionic reaction manifold ( Figure 1B ).…”