Cobalt-catalyzed alkene hydrogenation by reductive turnover

Article abstract of DOI:10.1016/j.tetlet.2021.153047

Earth abundant metal catalysts hold advantages in cost, environmental burden and chemoselectivity over precious metal catalysts. Differences in reactivity for a given metal center result from ligand field strength, which can promote reaction through either open- or closed-shell carbon intermediates. Herein we report a simple protocol for cobalt-catalyzed alkene reduction. Instead of using an oxidative turnover mechanism that requires stoichiometric hydride, we find a reductive turnover mechanism that requires stoichiometric proton. The reaction mechanism appears to involve coordination and hydrocobaltation of terminal alkenes.

Full text of DOI:10.1016/j.tetlet.2021.153047

Tetrahedron Letters 72 (2021) 153047
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Cobalt-catalyzed alkene hydrogenation by reductive turnover
Vincent van der Puyl a, Ruairi O. McCourt b, Ryan A. Shenvi a,
⇑
a Department of Chemistry, Scripps Research, 10550 North Torrey Lines Road, La Jolla, CA 92037, United States
b Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, The University of Dublin, Dublin 2, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
Earth abundant metal catalysts hold advantages in cost, environmental burden and chemoselectivity over
precious metal catalysts. Differences in reactivity for a given metal center result from ligand field
strength, which can promote reaction through either open- or closed-shell carbon intermediates.
Herein we report a simple protocol for cobalt-catalyzed alkene reduction. Instead of using an oxidative
turnover mechanism that requires stoichiometric hydride, we find a reductive turnover mechanism that
requires stoichiometric proton. The reaction mechanism appears to involve coordination and hydrocobal-
tation of terminal alkenes.
Received 2 March 2021
Revised 23 March 2021
Accepted 26 March 2021
Available online 31 March 2021
This paper is dedicated to Dale Boger, a
trusted colleague, mentor, friend and
recipient of the 2020 Tetrahedron Prize.
Ó 2021 Elsevier Ltd. All rights reserved.
Keywords:
Cobalt
Hydrogenation
Reduction
Alkene
Manganese
Introduction
with b-diketonate ligands and substitution of isopropanol with a
more reactive silane hydride donor. We, in turn, adapted Mukaiya-
Hydrogenation of alkenes finds use across scales to introduce
saturation and stereocenters [1]. Precious metal catalysts (Rh, Pt,
Pd) and hydrogen gas can be limited, however, by catalyst cost or
availability, ignition of hydrogen/oxygen mixtures, and high-pres-
sure requirements. The canonical Horiuti–Polanyi mechanism for
precious metal-catalyzed hydrogenation [2] involves alkene coordi-
nation (adsorption), metal-hydride migratory insertion and reduc-
tive elimination: traditional inner-sphere elementary steps
(Fig. 1A). In contrast, hydride complexes of earth abundant metals
like manganese, iron and cobalt can undergo an outer-sphere ele-
mentary step of metal-hydride hydrogen atom transfer (MHAT)
[3]. During attempts to induce reductive turnover of MHAT hydro-
genation (Fig. 1B) [4], we discovered a simple alkene reduction pro-
tocol that uses cheap reagents, avoids hydrogen gas and operates at
standard pressure and temperature. In contrast to our recent inves-
tigations of Co- and Mn-catalyzed alkene hydrofunctionalization,
this reaction likely involves an alkene coordination step.
ma’s modification to effect a hydrogenation of alkenes by replace-
ment of O2 with TBHP as a stoichiometric oxidant. An unusual
paradigm underlies this hydrogenation: a stoichiometric hydride
source and an oxidant are necessary for catalyst turnover and
therefore must be mutually compatible (Fig. 1B). This dual require-
ment of a stoichiometric reductant and stoichiometric oxidant can
complicate the merger of these MHAT cycles with cross-coupling
cycles [6]. Therefore, we sought to replace the [HÀ]/[O] combina-
tion with an [eÀ]/[H+] combination, so that metal hydride might
be formed by protonation of
a low valent metal complex
(Fig. 1B). Herein we report a method that takes advantage of this
reaction design, albeit to effect a coordinative hydrogenation of
terminal olefins (Fig. 1C).
Results and discussion
Screening for reductive hydrogenation initiated with manganese
(III) complexes in combination with stoichiometric manganese(0)
reductant in a variety of solvents, utilizing 4-phenylbutene (1a) as
substrate. These efforts failed to deliver product and our attention
turned to cobalt complexes. The Co(II)(salen) class was initially
examined for its hydrogenation activity in the presence of stoichio-
metric reductants such as titanium(III) salts, manganese(0), zinc(0),
and magnesium(0). None of these conditions provided product
Our work originated in reports by Drago that cobalt salen
complexes in ethanol at reflux under an aerobic atmosphere could
catalyze alkene hydration [5]. This hydration system was adapted
by Mukaiyama to a more practical variant by replacement of salens
⇑
Corresponding author.
E-mail address: rshenvi@scripps.edu (R.A. Shenvi).
https://doi.org/10.1016/j.tetlet.2021.153047
0040-4039/Ó 2021 Elsevier Ltd. All rights reserved.

V. van der Puyl, R.O. McCourt and R.A. Shenvi
Tetrahedron Letters 72 (2021) 153047
Table 1
Substrate scope of the reaction.a
Fig. 1. Reaction design.
either. Lewis acids were considered to enhance ligand lability and
facilitate catalyst reduction. A brief screen of inexpensive aluminum
salts revealed AlCl3 as a suitable Lewis acid to effect reduction, but
reaction only occurred in protic solvent. Along with a Co(II)(salen)
catalyst and manganese(0) in isopropanol, this combination of
reagents proved able to effect the reaction at ambient temperature
and pressure, providing 84% hydrogenation of 1a (as observed by
1H NMR spectroscopy against an internal standard). Other reduc-
tants failed to deliver product under these conditions. A brief screen
of other cobalt salts revealed that Co(OAc)2Á4H2O served as a supe-
rior catalyst, providing 2a with an isolated yield of 96%.
With conditions in hand, we next examined the scope of the
reaction (Table 1). Allylbenzene 1b and allylether 1c could be
hydrogenated to the corresponding products (2b-c). A range of
N-allylbenzamides could also be hydrogenated under the reaction
conditions (2d-l). Halides that are prone to reduction with
heterogenous palladium(0) catalysts remain untouched over the
course of this reaction (2j-k). N-Allylsulfonamides 2m-o are also
reduced, as are N-allylalkylamides such as 2p. There are limita-
tions to the reaction. For example, the reaction fails to hydro-
genate some allylethers, allylamides, and styrenes. 1,1-
Disubstiuted and internal olefins are unaffected by the reaction.
The reaction also deprotects silyl ethers. Further details can be
found in the ESI. We noted that gas evolution occurs at the begin-
ning of the reaction and hypothesized that the HCl generated by
reaction of AlCl3 with alcohol was reduced by Mn powder. Indeed,
we found that AlCl3 could be replaced with only 2 equivalents of
HCl and led to similar yields for representative substrates (1a, 1j,
and 1l) (Table 2).
a
Reagents and conditions: 0.2 mmol 1, 30 mol% Co(OAc)2Á4H2O, 1 equiv. AlCl3, 3
equiv. Mn powder (-325 mesh), 2 mL i-PrOH, 22 °C, 12–24 h, isolated yield reported.
Table 2
Examples with HCl instead of AlCl3.a
a
Reaction conditions: 0.1 mmol 1, 30 mol% Co(OAc)2Á4H2O, 2 equiv HCl/i-PrOH
solution (1–2 M), 3 equiv Mn powder (-325 mesh), 1 mL i-PrOH, 22 °C, 18 h, 1H NMR
yield reported.
1. Solvent (isopropanol) coordinates to Co(II) and undergoes b-
hydride elimination to afford a Co(II)–H. Migratory insertion
into the olefin substrate forms an alkylcobalt(II) complex. The
Co(II)–C bond is then protonated to afford hydrogenation pro-
duct (Scheme 1). (excluded)
2. Co(II) is reduced by Mn(0) to Co(I). The Co(I) species is proto-
nated to Co(III)–H. This species undergoes MHAT to the olefin
to generate the free radical and a Co(II) species. The alkyl radical
abstracts a hydrogen atom from Co(III)–H or solvent to afford
the hydrogenation product (Scheme 2). (excluded)
We then turned our attention to the mechanism of this reaction.
A few observations guided hypothesis and experiment. First, no
reaction occurred in the absence of added acid. Second, no reaction
occurred in the absence of Co salt or Mn reductant. Third, Mn pow-
der could be replaced with Zn powder, but Zn caused significant
variations in yield between runs. Fourth, different cobalt salts were
competent in the reaction and likely formed CoCl2 in situ [based on
the formation of a blue alcoholic solution].
In light of these observations, several hypotheses seemed
plausible:
2

V. van der Puyl, R.O. McCourt and R.A. Shenvi
Tetrahedron Letters 72 (2021) 153047
3. Co(II) is reduced by Mn(0) to Co(0 or I). The cobalt(0 or I) spe-
cies is protonated to Co(II or III)–H. This species undergoes
migratory insertion into the olefin to afford a Co(II or III)–alkyl
species. Protonation of the Co–C bond affords hydrogenation
product and a Co(II or III) species that is reduced by Mn(0) to
close the catalytic cycle (Scheme 3).
4. Co(II) precatalysts are reduced in situ by Mn(0) to afford Co(0 or
I) capable of undergoing oxidative addition with hydrogen gas
generated by reaction of solvent with AlCl3, generating HCl that
goes on to react with Mn(0), affording H2 and MnCl2. The Co(II
or III) dihydride undergoes 1,2-insertion and reductive elimina-
tion sequence to afford hydrogenated product (Scheme 4).
(excluded)
Scheme 3.
5. Mn(0) reacts with the generated HCl to afford Cl–Mn(II)–H. This
species undergoes ligand exchange with Co(II) to afford a Co
(II)–H that undergoes 1,2-insertion with the olefin substrate.
Subsequent protonation of the Co(II)–C bond affords product
(Scheme 5). (excluded)
Subsequent experiments refute a number of these mechanisms.
Exclusion of manganese powder led to complete arrest of the
reaction, so mechanism 1 was excluded since this mechanism
had no obvious role for manganese. Substrate 3 failed to undergo
any cyclization (only product 4 is observed by GCMS) (Fig. 2A).
Therefore, either a radical never formed or the radical-metal cage
pair exhibited very high fractional cage efficiency (Fc). We recently
found that Co(salen) complexes undergo HAT to generate radical
pairs with apparently low Fc, leading to efficient radical cyclization
onto arenes. For this reason, the fastest reacting substrates tended
to be 1,1-disubstituted alkenes, which form tertiary radicals and
resist collapse to an organometallic. In contrast, these reductions
with Co(II) and Mn(0) only react with terminal alkenes, inconsis-
tent with an MHAT mechanism [7]. Thus, mechanism 2 may be
ruled out. When argon is bubbled through the reaction to remove
Scheme 4.
Scheme 1.
Scheme 5.
hydrogen gas before addition of olefin, product is still observed
(Fig. 2B). The reaction also fails to proceed in the presence of
catalytic manganese and hydrogen atmosphere (Fig. 2C). Therefore,
mechanism
4 may be ruled out. When MnCl2 is used in
combination with PhSiH3 instead of Mn(0)/HCl, the reaction fails
to proceed (Fig. 2D). On the basis of this observation and the ability
to replace Mn(0) with Zn(0), mechanism (5) may be excluded from
consideration (it is possible that the Si–H/Mn–Cl ligand exchange
is endergonic and does not proceed under the reaction conditions).
Put together, these experiments leave mechanism 3 as a plausible
pathway for this reduction. Further work is required to elucidate
the complete details, but this rough sketch may provide guidance
for future work in reductive protonation to LnCo-H complexes,
especially those with weak-field ligands [8].
Scheme 2.
3

V. van der Puyl, R.O. McCourt and R.A. Shenvi
Tetrahedron Letters 72 (2021) 153047
Appendix A. Supplementary data
Supplementary data (experimental procedures and characteri-
zation for new compounds) to this article can be found online at
https://doi.org/10.1016/j.tetlet.2021.153047.
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We have disclosed a method for the hydrogenation of terminal
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olefins catalyzed by cobalt and mediated by a stoichiometric
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(VWR/ ChemImpex): 0.085 $/g @ 1 kg; i-PrOH (anhydrous) (Acros):
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Declaration of Competing Interest
(c) S.A. Green, T.R. Huffman, R.O. McCourt, V.A. van der Puyl, R.A. Shenvi,
Hydroalkylation of olefins to form quaternary carbons, J. Am. Chem. Soc. 141
(2019) 7709–7714.
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
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isomerization, J. Am. Chem. Soc. 136 (2014) 16788–16791.
[8] S.L. Shevick, C.V. Wilson, S. Kotesova, D. Kim, P.L. Holland, R.A. Shenvi, Catalytic
hydrogen atom transfer to alkenes: a roadmap for metal hydrides and radicals,
Chem. Sci. 11 (2020) 12401–12422.
Acknowledgements
We are grateful for support by the NSF (CHE 1955922) and the
NIH (R35 GM122606) (R.A.S.), the Fulbright Scholarship Program
(R.O.M.) and the Skaggs Graduate School (V.v.d.P.).
4