C(sp3)-H functionalizations of light hydrocarbons using decatungstate photocatalysis in flow

Article abstract of DOI:10.1126/science.abb4688

Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community. Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically required to enable C(sp3)-H bond cleavage, barring potential applications in synthetic organic chemistry. Here, we report a general and mild strategy to activate C(sp3)-H bonds in methane, ethane, propane, and isobutane through hydrogen atom transfer using inexpensive decatungstate as photocatalyst at room temperature. The corresponding carbon-centered radicals can be effectively trapped by a variety of Michael acceptors, leading to the corresponding hydroalkylated adducts in good isolated yields and high selectivity (38 examples).

Full text of DOI:10.1126/science.abb4688

RESEARCH
fluorinations (21), arylations (22), and other
C–C bond formations (23). However, because
of the gaseous nature and the low solubility of
light alkanes in organic solvents, we reasoned
that the use of flow technology is indispens-
able to facilitate the gas-liquid decatungstate-
mediated processes (Fig. 1C) (24). The short
length scales in microflow reactors (typically
<1-mm optical path) provide a homogeneous
irradiation of the entire reaction medium,
allowing for the efficient generation of alkyl
radicals (25). Furthermore, by increasing the
pressure in the reactor through use of opera-
tionally simple back-pressure regulators, the
gaseous alkanes can be forced into the liquid
phase, increasing the odds of C(sp3)–H bond
activation through decatungstate photocatalysis
(26). Finally, flow processing of these combusti-
ble gases can be done safely in microreactors,
and the conditions can be readily scaled (27, 28).
Among all volatile alkanes, methane is the
hardest one to activate because of high BDE
of these C–H bonds (BDE = 105 kcal/mol)
(Fig. 1B) (29). However, if we can successfully
split methane bonds with decatungstate HAT
photocatalysis, cleaving the C–H bond in ethane
(BDE = 101 kcal/mol) and other volatile aliphatic
feedstock materials, such as propane (BDE =
99 kcal/mol) and isobutane (BDE = 96.5 kcal/
mol), should be within reach. Indeed, we car-
ried out trapping experiments with TEMPO
(tetramethylpiperidine-1-oxyl), a stable aminoxyl
radical, and the trapped adducts of methane,
ethane, propane, and isobutane gave credence
to the feasibility of our approach (Fig. 1D). No-
tably, because of the stability of the generated
radical and the lower BDE of the C–H bond,
high selectivity was observed for the formation
of secondary and tertiary C(sp3)–O bonds from
propane and isobutane, which is in contrast to
a recently reported HAT approach using alkoxy
radicals (14).
We began our investigation into the proposed
C(sp3)–H functionalization of light hydrocarbons
by exposing isobutane and benzylidenemalononi-
trile in the presence of tetrabutylammonium
decatungstate (TBADT) in acetonitrile:H2O
(7:1), which provides both good solubility and
good reactivity of the photocatalyst, to UV-A
light [365-nm light-emitting diodes (LEDs),
60 W]. For a number of substrates, limited
solubility was observed upon addition of water.
However, this could be circumvented by car-
rying out the reactions in neat acetonitrile.
Furthermore, acetonitrile, despite the relatively
low BDE (96 to 97 kcal/mol) of its C–H bonds
(30), is also inert under the given HAT reaction
conditions. This can be attributed to a polarity
mismatch between decatungstate and the
C(sp3)–H bonds in acetonitrile. All the experi-
ments were carried out in a standardized,
commercially available Vapourtec UV-150 pho-
tochemical flow reactor, which should enable
reproducibility of the results. After careful
ORGANIC CHEMISTRY
C(sp3)–H functionalizations of light hydrocarbons
using decatungstate photocatalysis in flow
Gabriele Laudadio1*, Yuchao Deng1,2,3*, Klaas van der Wal1, Davide Ravelli4, Manuel Nuño5,
Maurizio Fagnoni4, Duncan Guthrie5, Yuhan Sun2,3, Timothy Noël1†
Direct activation of gaseous hydrocarbons remains a major challenge for the chemistry community.
Because of the intrinsic inertness of these compounds, harsh reaction conditions are typically
required to enable C(sp3)–H bond cleavage, barring potential applications in synthetic organic chemistry.
Here, we report a general and mild strategy to activate C(sp3)–H bonds in methane, ethane, propane,
and isobutane through hydrogen atom transfer using inexpensive decatungstate as photocatalyst
at room temperature. The corresponding carbon-centered radicals can be effectively trapped by a
variety of Michael acceptors, leading to the corresponding hydroalkylated adducts in good isolated
yields and high selectivity (38 examples).
ne of the most challenging reactions in
organic synthesis is the selective func-
tionalization of C(sp3)–H bonds that
lack activation by proximal functional
groups (1). The conversion of light
can be easily converted into organometallic
reagents, which can be engaged as nucleophiles
in a variety of transition metal–catalyzed C–C
bond forming reactions (9).
O
A general synthetic strategy that enables the
selective and direct activation of a diverse set
of light hydrocarbons under mild reaction
conditions remains a challenge, suffering from
at least one drawback with regard to substrate
scope (10–13), practicality, and selectivity (14).
The development of such a transformation
would be particularly useful, given the broad
availability and the inexpensive nature of these
starting materials. Furthermore, the reduction
in synthetic steps would allow for streamlined
reaction sequences and decreased waste gener-
ation. However, we reasoned that two funda-
mental problems needed to be addressed to
succeed: First, a suitable transformation would
require the selective cleavage of very strong
aliphatic C–H bonds [bond dissociation energy
(BDE) = 96.5 to 105 kcal/mol] (Fig. 1B), and
second, the handling of these gaseous alkanes
presents several technological challenges to
bring them into close proximity with a suitable
catalyst and reaction partner.
alkanes to high–value added chemicals has
especially been a key objective for the synthetic
community in the past decades, yet with limited
success so far (2–4). Up to now, strategies to
introduce such alkyl fragments into organic
scaffolds necessitate prefunctionalization of
the hydrocarbons to increase their reactivity
(Fig. 1A). Volatile alkanes are typically con-
verted into alkyl electrophiles through halo-
genation by using chlorine or bromine gas at
elevated temperatures (>500°C) or by using
light activation (5, 6). These radical chain pro-
cesses result in low-yielding and unselective
transformations, with demands for subsequent
energy-intensive and elaborate purification and
recycling processes [for the effluent guidelines
in the chlorine and chlorinated hydrocarbon
manufacturing industry, see (7)]. Despite the
apparent drawbacks, these classical halo-
genation strategies are being carried out on a
multi–metric ton scale to prepare a variety of
halogenated compounds that are key for the
production of most pharmaceuticals, agrochem-
icals, materials, and other industrial chemicals
(8). In synthetic organic chemistry, alkyl halides
are widely used as electrophiles in nucleophilic
substitution reactions or serve as substrates for
elimination reactions to install double bonds
regioselectively. Furthermore, alkyl halides
Seeking to address these challenges, we
wondered if a photoexcited decatungstate
anion (*[W10O32]
4−) could sunder effectively
the strong and nonactivated C–H bonds of
light alkanes (Fig. 1A). W10O324− is a versatile
and inexpensive polyoxometalate-based hydro-
gen atom transfer (HAT) photocatalyst that can
abstract hydrogen atoms from C(sp3)–H frag-
ments upon activation by near–ultraviolet
(UV) light irradiation (~365 nm) (15–18). The
resulting carbon-centered radicals are nucleo-
philic and might be readily engaged in C–C
bond forming reactions, thereby effectively
bypassing the requirement for more-elaborate
reaction strategies while expanding the syn-
thetic toolbox of available alkyl reagents. To
1Micro Flow Chemistry and Synthetic Methodology,
Department of Chemical Engineering and Chemistry,
Eindhoven University of Technology, Eindhoven, Netherlands.
2School of Physical Science and Technology, ShanghaiTech
University, Shanghai 201210, P. R. China. 3Shanghai
Advanced Research Institute, Chinese Academy of Sciences,
Shanghai 201210, P. R. China. 4PhotoGreen Lab, Department
of Chemistry, University of Pavia, Pavia 27100, Italy.
5Vapourtec, Fornham St Genevieve, Bury St Edmunds,
Suffolk IP28 6TS, UK.
4−
date, W10O32 photocatalysis has enabled a
number of synthetically useful C(sp3)–H func-
tionalizations, including oxidations (19, 20),
*These authors contributed equally to this work.
†Corresponding author. Email: t.noel@tue.nl
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Fig. 1. Decatungstate enables the direct C(sp3)–H activation of light hydrocarbons. (A) Photocatalytic scission of strong C(sp3)–H bonds of volatile alkanes
allows us to generate nucleophilic alkyl radicals and to bypass the use of halogenated alkanes or organometallic reagents. (B) BDE of some common gaseous alkanes
(35). (C) Conversion of gaseous alkanes into functionalized alkanes by blending TBADT photocatalysis, the use of gases, and flow chemistry. liq., liquid. (D) TEMPO
trapping experiments showing the feasibility of the outlined strategy of HAT activation of aliphatic substrates (results obtained with GC-MS). Me, methyl.
optimization of the reaction conditions (sup-
plementary materials), we observed that the
targeted compound 1 could be obtained in
an excellent isolated yield of 91% by using
1 mol % of TBADT as a HAT photocatalyst
(Fig. 2). Critical to the success of the reaction
was the increase of the reaction pressure up
to 10 bar, which results in a complete liquefac-
tion of the gas and thus avoids gas-to-liquid
mass transfer limitations. Moreover, 4.3 equiv-
alents of isobutane were used to obtain opti-
mal yields, whereas larger amounts did not lead
to a further yield improvement (supplemen-
tary materials). Furthermore, classical conjugate
addition strategies require transition metal
catalysts and prefunctionalized nucleophilic
organometallic reagents (31). The stepwise and
lengthy procedure to prepare such nucleophilic
reagents stands in marked contrast to the
single-step HAT activation of gaseous alkanes
as shown herein.
radicals, yielding the targeted hydroalkylated
compounds in excellent isolated yields (82 to
93%) and very good selectivity for the install-
ment of a tertiary butyl group [tBu versus isobutyl
(iBu): ~96:4]. Halogenated benzylidene malono-
nitrile substrates (3 to 5) can be engaged in
the transformation as well, providing requisite
handles to be converted into diverse organic
molecules by using classical cross-coupling
strategies. Methyl trans-a-cyanocinnamate
is another efficient substrate for scavenging
tertiary butyl radicals, yielding the targeted
compound 8 in 85% isolated yield. Whereas
for isobutyl radicals both diastereomers were
formed in equal amounts, the trapping of the
more sterically demanding tertiary butyl radical
resulted in a relatively high diastereomeric
ratio (d.r. = 3.1:1). Other traps, such as triethyl
ethylenetricarboxylate, N-phenylmaleimide,
and 3-methylene-2-norbornanone, resulted in
the formation of synthetically useful building
blocks (9 to 11) in good to excellent isolated
yields (71 to 90%) and excellent selectivity in
favor of the tertiary butyl–appended molecules.
Complete endoselectivity was observed for
compound 11, which is consistent with a hy-
drogen back-donation from the reduced pho-
tocatalyst from the less hindered side of the
norbornane moiety (Fig. 3A). We did not ob-
serve any significant amount of by-products as
detected by gas chromatography–mass spec-
trometry (GC-MS) analysis (<2%) for a variety
of reasons. C–H abstraction from the starting
Michael acceptors is not a competitive process,
because in most cases, no labile hydrogens are
present. Furthermore, C–H cleavage in the al-
kylated products did not lead to another C–H
activation event, in part because of a polarity
mismatch (15). TBADT* has a marked prefer-
ence for the abstraction of nucleophilic hydro-
gens and avoids dissociating electrophilic C–H
bonds such as those present in a-position to
the electron-withdrawing functional groups.
Moreover, despite the presence of labile ben-
zylic hydrogens in some of the products, no by-
products are generated, because of a combi-
nation of the voluminous size of TBADT and
the steric hindrance at those benzylic posi-
tions (15). Finally, the presence of an excess of
gaseous alkanes prevents hydrogen abstrac-
tion from any other organic compound in the
reaction mixture.
With optimized reaction conditions in hand,
we next explored the scope of the transfor-
mation (Fig. 2). A variety of electronically dis-
tinct benzylidenemalononitriles (1 to 7) could
serve as highly efficient radical traps for the
photocatalytically generated carbon-centered
This protocol was also found to enable the ef-
ficient activation of propane, a key constituent
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Fig. 2. Scope of the decatungstate C(sp3)–H functionalizations of light hydrocar-
bons. All yields are those of isolated products (average of two runs). The reported
selectivities are determined with GC-MS. [*]Standard conditions for the decatungstate
C(sp3)–H functionalizations of isobutane: olefin (1 equiv, 0.1 M), isobutane (4.3 equiv),
TBADT (1.0 mol %), CH3CN:H2O (7:1), 10-bar pressure, 60 W of 365-nm LEDs, 4-hour
reaction time, room temperature. Reported selectivity reflects the tBu:iBu ratio.
[†]Standard conditions for the decatungstate C(sp3)–H functionalizations of propane:
olefin (1 equiv, 0.1 M), propane (4.1 equiv), TBADT (1.0 mol %), CH3CN:H2O (7:1), 10-bar
pressure, 60 W of 365-nm LEDs, 4-hour reaction time, room temperature. Reported
selectivity reflects the iPr:nPr ratio. [‡]Standard conditions for the decatungstate C(sp3)–H
functionalizations of ethane: olefin (1 equiv, 0.1 M), ethane (8 equiv), TBADT (2.0 mol %),
CH3CN:H2O (7:1), 25-bar pressure, 60 W of 365-nm LEDs, 8-hour reaction time, room tem-
perature. [§]Standard conditions for the decatungstate C(sp3)–H functionalizations
of methane: olefin (1 equiv, 0.02 M), methane (20 equiv), TBADT (5.0 mol %), CD3CN:H2O
(7:1), 45-bar pressure, 150 W of 365-nm LEDs, 6-hour reaction time, room temperature.
[¶]C(Michael acceptor) = 0.05 M. [#]Solvent: neat CH3CN. [**]Solvent: neat CD3CN. Et, ethyl.
Laudadio et al., Science 369, 92–96 (2020)
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RESEARCH
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Fig. 3. Proposed mechanism of the decatungstate C(sp3)–H functionalizations of light hydrocarbons. (A) Proposed mechanistic rationale based on our
observations. (B) Importance of photon flux and catalyst loading for the effectiveness of the decatungstate C(sp3)–H functionalization of propane.
of liquid petroleum gas. Propyl radicals could
be scavenged by a variety of Michael accep-
tors (12 to 22), affording the targeted hy-
droalkylated compounds in good to excellent
isolated yields (73 to 92%). A high selectivity
was obtained for the isopropyl derivative (iPr),
with selectivities similar to those obtained
in the TEMPO trapping experiments [iPr ver-
sus n-propyl (nPr): ~85:15] (Fig. 1D). The high
selectivity in the C–H cleavage is notable
despite the low difference in BDE between
secondary and primary hydrogens (99 ver-
sus 101 kcal/mol) and despite the unfavorable
relative abundance (six primary hydrogens ver-
sus two secondary ones). With methyl trans-
a-cyanocinnamate as the substrate, a significant
diastereomeric induction was observed for the
trapping of the isopropyl radical (d.r. = 2.7:1
versus d.r. = 1:1 for n-propyl), showcasing the
significance of sterical hindrance in the ob-
served selectivity.
Another notable gaseous hydrocarbon is
ethane, which is isolated from natural gas or
obtained as a petrochemical by-product of
petroleum refining. It is mainly used as a
feedstock for ethylene production, required for
the fabrication of polyethylene, which accounts
for 34% of the total plastics market. Similar
to isobutane and propane, ethane could be
engaged in the developed C(sp3)–H activation
protocol using 2 mol % of TBADT and 25 bar
of pressure to liquefy the gaseous hydrocarbon.
Good isolated yields (62 to 87%) were obtained
for a diverse set of hydroethylated compounds
(23 to 33).
though such a strategy would require cleaving
the strongest C(sp3)–H bond (BDE = 105 kcal/
mol), small changes in the reaction protocol
(45-bar pressure and 5.0 mol % TBADT) al-
lowed us to obtain synthetically useful amounts
of the corresponding adducts (34 to 38, 38 to
48%) in only 6 hours of residence time. Because
of the substantially weaker C–H bond of ace-
tonitrile (BDE = 93 kcal/mol) compared with
that of methane, the innate selectivity of deca-
tungstate, imparted by the electrophilic na-
ture of its excited state, could be overruled,
and substantial amounts of product derived
from CH3CN activation were observed as well
(supplementary materials). This problem could,
however, effectively be overcome by using d3-
acetonitrile as a solvent. Investigations to re-
place this rather exotic solvent with a cheaper
and greener alternative are currently ongoing
in our laboratory.
A plausible mechanism for the decatungstate
C(sp3)–H functionalizations of light hydrocar-
bons is outlined in Fig. 3A. Upon absorption
of UV-A light, decatungstate reaches a singlet
excited state, which rapidly relaxes to the
actual reactive state, wO (18). The reactivity of
wO originates from the formation of highly
electrophilic oxygen centers, which can ab-
stract hydrogen atoms yielding the desired
carbon-centered radicals. The power of the
light source in combination with a suitable
catalyst loading is extremely relevant in photo-
chemical processes (32), and this is especially
true for the challenging transformation reported
herein. As can be seen from Fig. 3B, the acti-
vation of propane is particularly slow when a
strip of 32-W UV-A LEDs was used. However,
the reaction can be boosted by using 60-W
UV-A LEDs, requiring only 4 hours to reach full
conversion. For more-challenging transforma-
tions, such as the activation of methane, an even
stronger light source of 150 W was required to
coax the C(sp3)–H functionalization process.
The nucleophilic carbon-centered radicals sub-
sequently undergo a conjugate addition onto a
suitable Michael acceptor. The carbon-centered
radicals could be trapped with TEMPO, provid-
ing isomeric ratios for propane and isobutane
similar to those observed in the final products
(Fig. 1D). The catalytic cycle is finally closed by
hydrogen back-donation, which affords the tar-
geted hydroalkylated product.
Given the straightforward preparation (33)
of the photocatalyst and the starting materials
and the mild reaction conditions, we believe
that the corresponding processes outlined herein
can be considered ideal from the vantage point
of feedstock upgrading. The ability to directly
engage gaseous hydrocarbons as coupling part-
ners in C–C coupling reactions removes the
requirement of prefunctionalization and in-
creases the atom efficiency of this important
class of transformations. Whereas the through-
put of a single microreactor is negligible from
a production standpoint, the use of intensi-
fied reactors, such as a photo-spinning disk
reactor, should enable higher production ca-
pacities (34).
REFERENCES AND NOTES
1. J. F. Hartwig, M. A. Larsen, ACS Cent. Sci. 2, 281–292
(2016).
2. J. F. Hartwig, J. Am. Chem. Soc. 138, 2–24 (2016).
3. H. Li, B.-J. Li, Z.-J. Shi, Catal. Sci. Technol. 1, 191–206
(2011).
4. R. H. Crabtree, J. Chem. Soc., Dalton Trans. 2001, 2437–2450
(2001).
5. M. Rossberg et al., in Ullmann's Encyclopedia of Industrial
Chemistry (Wiley, 2006).
Finally, we turned our attention to the ac-
tivation of methane, one of the most abun-
dantly available carbon-based feedstocks, using
this decatungstate-enabled HAT protocol. Al-
Laudadio et al., Science 369, 92–96 (2020)
3 July 2020
4 of 5

RESEARCH
| REPORT
6. D. J. Reed, in Kirk‐Othmer Encyclopedia of Chemical
Technology, vol. 6 (Wiley, 2000), pp. 226–253.
7. U.S. Environmental Protection Agency (EPA), Chlorine and
Chlorinated Hydrocarbon Manufacturing Industry (2004);
www.epa.gov/eg/chlorine-and-chlorinated-hydrocarbon-
manufacturing-industry
8. R. Lin, A. P. Amrute, J. Pérez-Ramírez, Chem. Rev. 117,
4182–4247 (2017).
9. C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 111, 1780–1824
20. D. M. Schultz et al., Angew. Chem. Int. Ed. 56, 15274–15278
(2017).
ACKNOWLEDGMENTS
We thank F. Gallucci (TU/e) for the kind donation of the light
alkanes. Funding: We acknowledge financial support from the
Dutch Science Foundation (NWO) for a VIDI grant for T.N.
(SensPhotoFlow, no. 14150). Y.D.’s stay at the Eindhoven University
of Technology was financially supported by the China Scholarship
Council (CSC). Author contributions: T.N., G.L., and M.F. conceived
the idea for this work. G.L., Y.D., and K.v.d.W. carried out the
experiments. T.N., Y.S., M.F., and D.R. provided guidance with
regard to the catalyst performance and the substrate scope. T.N.,
M.N., and D.G. provided direction for the flow experiments. T.N.
wrote the manuscript with input from all authors. Competing
interests: M.N. and D.G. both work at Vapourtec, the company
that developed the Vapourtec UV-150 used in this study. Data and
materials availability: All data are available in the main text or
the supplementary materials.
21. S. D. Halperin, H. Fan, S. Chang, R. E. Martin, R. Britton,
Angew. Chem. Int. Ed. 53, 4690–4693 (2014).
22. I. B. Perry et al., Nature 560, 70–75 (2018).
23. J. J. Murphy, D. Bastida, S. Paria, M. Fagnoni, P. Melchiorre,
Nature 532, 218–222 (2016).
24. M. B. Plutschack, B. Pieber, K. Gilmore, P. H. Seeberger,
Chem. Rev. 117, 11796–11893 (2017).
25. D. Cambié, C. Bottecchia, N. J. W. Straathof, V. Hessel, T. Noël,
Chem. Rev. 116, 10276–10341 (2016).
26. C. J. Mallia, I. R. Baxendale, Org. Process Res. Dev. 20,
327–360 (2016).
(2011).
10. Z. Jin et al., Science 367, 193–197 (2020).
11. G. Chen et al., Angew. Chem. Int. Ed. 58, 17528–17551
(2019).
12. A. Koppaka et al., Angew. Chem. Int. Ed. 58, 2241–2245 (2019).
13. H.-P. Deng, Q. Zhou, J. Wu, Angew. Chem. Int. Ed. 57,
12661–12665 (2018).
14. A. Hu, J.-J. Guo, H. Pan, Z. Zuo, Science 361, 668–672
(2018).
15. D. Ravelli, M. Fagnoni, T. Fukuyama, T. Nishikawa, I. Ryu,
ACS Catal. 8, 701–713 (2018).
27. B. Gutmann, D. Cantillo, C. O. Kappe, Angew. Chem. Int. Ed. 54,
6688–6728 (2015).
28. N. Kockmann, P. Thenée, C. Fleischer-Trebes, G. Laudadio,
T. Noël, React. Chem. Eng. 2, 258–280 (2017).
29. N. J. Gunsalus et al., Chem. Rev. 117, 8521–8573 (2017).
30. Y.-R. Luo, Handbook of Bond Dissociation Energies in Organic
Compounds (CRC Press, 2002).
31. K. Fagnou, M. Lautens, Chem. Rev. 103, 169–196 (2003).
32. H. E. Bonfield et al., Nat. Commun. 11, 804 (2020).
33. D. Ravelli, S. Protti, M. Fagnoni, Acc. Chem. Res. 49,
2232–2242 (2016).
SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/369/6499/92/suppl/DC1
Materials and Methods
Figs. S1 to S13
Tables S1 to S10
NMR Data
References (36–49)
16. L. Capaldo, D. Ravelli, Eur. J. Org. Chem. 2017, 2056–2071
(2017).
17. M. D. Tzirakis, I. N. Lykakis, M. Orfanopoulos, Chem. Soc. Rev.
38, 2609–2621 (2009).
18. C. Tanielian, Coord. Chem. Rev. 178-180, 1165–1181 (1998).
19. G. Laudadio et al., Angew. Chem. Int. Ed. 57, 4078–4082
(2018).
34. A. Chaudhuri et al., ChemRxiv [Preprint] (2020).
35. S. J. Blanksby, G. B. Ellison, Acc. Chem. Res. 36, 255–263
(2003).
26 February 2020; accepted 6 May 2020
10.1126/science.abb4688
Laudadio et al., Science 369, 92–96 (2020)
3 July 2020
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C(sp3)−H functionalizations of light hydrocarbons using decatungstate photocatalysis in flow
Gabriele Laudadio, Yuchao Deng, Klaas van der Wal, Davide Ravelli, Manuel Nuño, Maurizio Fagnoni, Duncan Guthrie,
Yuhan Sun and Timothy Noël
Science 369 (6499), 92-96.
DOI: 10.1126/science.abb4688
Using hydrocarbons as reagents
Adding small alkyl groups to complex molecules usually relies on alkyl halide reagents. Laudadio et al. now report
a convenient method to add ethane and propane directly across conjugated olefins with no prefunctionalization or
byproducts (see the Perspective by Oksdath-Mansilla). The C−H bond scission in this hydroalkylation is accomplished by
a decatungstate photocatalyst that also acts as a hydrogen atom transfer agent to complete the process. The reaction,
optimized under flow conditions, works with methane as well, albeit with lower efficiency.
Science, this issue p. 92; see also p. 34
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