We report the synthesis and reactivity of a model of [Fe]-hydrogenase derived from an anthracene-based scaffold that includes the endogenous, organometallic acyl(methylene) donor. In comparison to other non-scaffolded acyl-containing complexes, the complex described herein retains molecularly well-defined chemistry upon addition of multiple equivalents of exogenous base. Clean deprotonation of the acyl(methylene) C–H bond with a phenolate base results in the formation of a dimeric motif that contains a new Fe–C(methine) bond resulting from coordination of the deprotonated methylene unit to an adjacent iron center. This effective second carbanion in the ligand framework was demonstrated to drive heterolytic H 2 activation across the Fe( ii ) center. However, this process results in reductive elimination and liberation of the ligand to extrude a lower-valent Fe–carbonyl complex. Through a series of isotopic labelling experiments, structural characterization (XRD, XAS), and spectroscopic characterization (IR, NMR, EXAFS), a mechanistic pathway is presented for H 2 /hydride-induced loss of the organometallic acyl unit ( i.e. pyCH 2 –CO → pyCH 3 +CO). The known reduced hydride species [HFe(CO) 4 ] − and [HFe 3 (CO) 11 ] − have been observed as products by 1 H/ 2 H NMR and IR spectroscopies, as well as independent syntheses of PNP[HFe(CO) 4 ]. The former species ( i.e. [HFe(CO) 4 ] − ) is deduced to be the actual hydride transfer agent in the hydride transfer reaction (nominally catalyzed by the title compound) to a biomimetic substrate ([ Tol Im](BAr F ) = fluorinated imidazolium as hydride acceptor). This work provides mechanistic insight into the reasons for lack of functional biomimetic behavior (hydride transfer) in acyl(methylene)pyridine based mimics of [Fe]-hydrogenase.
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Access to unsaturated bicyclic lactones by overriding conventional C(sp3)–H site selectivity
Transition metal catalysis plays a pivotal role in transforming unreactive C–H bonds. However, regioselective activation of distal aliphatic C–H bonds poses a tremendous challenge, particularly in the absence of directing templates. Activation of a methylene C–H bond in the presence of methyl C–H is underexplored. Here we show activation of a methylene C–H bond in the presence of methyl C–H bonds to form unsaturated bicyclic lactones. The protocol allows the reversal of the general selectivity in aliphatic C–H bond activation. Computational studies suggest that reversible C–H activation is followed by β-hydride elimination to generate the Pd-coordinated cycloalkene that undergoes stereoselective C–O cyclization, and subsequent β-hydride elimination to provide bicyclic unsaturated lactones. The broad generality of this reaction has been highlighted via dehydrogenative lactonization of mid to macro ring containing acids along with the C–H olefination reaction with olefin and allyl alcohol. The method substantially simplifies the synthesis of important bicyclic lactones that are important features of natural products as well as pharmacoactive molecules.
more » « less- Award ID(s):
- 2029932
- PAR ID:
- 10553776
- Publisher / Repository:
- Nature publishing group
- Date Published:
- Journal Name:
- Nature Chemistry
- Volume:
- 15
- Issue:
- 11
- ISSN:
- 1755-4330
- Page Range / eLocation ID:
- 1626 to 1635
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Herein, we report the palladium‐catalyzed direct arylation of unactivated aliphatic C−H bonds in free primary amines. This method takes advantage of an
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41557-023-01295-x
