Radical Carbonyl Propargylation by Dual Catalysis

Article abstract of DOI:10.1002/anie.202011996

Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl₃ could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.

Full text of DOI:10.1002/anie.202011996

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Radical Carbonyl Propargylation via Dual Catalysis
Authors: Huan-Ming Huang, Peter Bellotti, Constantin Daniliuc, and
Frank Glorius
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202011996
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
Radical Carbonyl Propargylation by Dual Catalysis
Huan-Ming Huang,[a] Peter Bellotti,[a] Constantin Daniliuc[a] and Frank Glorius[a]*
Dedicated to Professor Carsten Bolm on the occasion of his 60th birthday
[a] Dr. H.-M. Huang, Mr. P. Bellotti, Dr. C. Daniliuc and Prof. Dr. F. Glorius
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany
E-mail: glorius@uni-muenster.de
Supporting information for this article is given via a link at the end of the document.
Abstract: Carbonyl propargylation has been established as a
valuable tool in the realm of carbon-carbon bond forming reactions.
The 1,3-enyne moiety has been recognized as an alternative
pronucleophile in the above transformation through an ionic
mechanism. Herein, we report for the first time the radical carbonyl
propargylation via dual chromium/photoredox catalysis. A library of
valuable homopropargylic alcohols bearing all-carbon quaternary
centers could be obtained through
a catalytic radical three-
component coupling of 1,3-enynes, aldehydes and suitable radical
precursors (41 examples). This redox-neutral multi-component
reaction occurs under very mild conditions and shows high functional
group tolerance. Remarkably, bench-stable, non-toxic and
inexpensive CrCl3 could be employed as a chromium source.
Preliminary mechanistic investigations suggest
a radical-polar
crossover mechanism, which offers a complementary and novel
approach towards the preparation of valuable synthetic architectures
from simple chemicals.
Introduction
Addition reactions of organometallic reagents to carbonyls stand
among the most fundamental chemical transformations and
represent a pivotal synthetic strategy in organic chemistry since
their discovery by Victor Grignard, who received the Nobel prize
in 1912.[1] In this realm, carbonyl propargylation has been
established as the most straightforward strategy to construct
versatile homopropargylic alcohols.[2] Typically, organometallic
reagents such as propargyl or allenyl metal species have to be
used, thus hampering broad functional group compatibility and
often requiring relatively harsh conditions.[2] Alternatively, low-
Scheme 1. (A) Nozaki-Hiyama-Kishi reaction in carbonyl propargylation; (B)
1,3-Enyne as a pronucleophile in carbonyl reactions (ionic mechanism); (C)
This work: radical carbonyl propargylation via dual Cr/photoredox catalysis.
valent
metal-catalyzed
(mediated)
reductive
carbonyl
propargylation has become a popular class of methods.[2a] This
reactive pattern is epitomized by the Nozaki-Hiyama-Kishi (NHK)
reaction,[3] which has been widely explored since its discovery in
1977.[4] Thanks to the mild conditions and excellent functional
group compatibility, Cr(II) mediated carbonyl propargylation has
1,3-Enynes have been widely employed as alternative
pronucleophiles in the carbonyl addition chemistry (Scheme
1B).[13] Carbonyl dienylation could be successfully achieved
when rhodium[14] or nickel[15] are employed as catalysts (Scheme
1B - route I). In 2008, Krische and co-workers reported the first
example of reductive carbonyl propargylation using a ruthenium
catalyst.[16a] Moreover, elegant examples of enantioselective
enyne-mediated propargylation have also been successfully
achieved (Scheme 1B - route II).[16b-c] In 2013, a Ni-catalyzed
three-component coupling reaction of 1,3-enynes, carbonyls,
and dimethylzinc to construct allenyl alcohols was reported by
Kimura (Scheme 1B - route III).[17] Later on, the elegant cross
coupling reactions between 1,3-enynes and carbonyls using a
been widely investigated by Goré,[5] Nozaki
&
Hiyama,[6]
Knochel[7] and others.[3] Fostered by the remarkable contribution
in the development of catalytic NHK reactions by Fürstner and
co-workers,[4d-e] Cozzi & Umani-Ronchi developed the first
enantioselective chromium catalyzed carbonyl propargylation in
2000.[8] Later on, Nakada,[9] Kishi[10] and Sigman[11] further
explored in this area in regard to ligand design[9,11] and total
synthesis applications.[10] However, stoichiometric metallic
reductants and additives could not be avoided in chromium
catalyzed NHK reactions (Scheme 1A).[12]
1
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10.1002/anie.202011996
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RESEARCH ARTICLE
copper catalyst have been reported by Hoveyda[18a]
,
demonstrated that the process can tolerate wet solvents, higher
reaction temperatures and even scale-up (3.0 mmol) with
minimal to negligible effect on the yield. Furthermore,
commercially available dry solvents could be used under inert
atmosphere without the need of additional degassing, thus
simplifying the operational set-up (medium O2). On the other
hand, the absence of inert atmosphere, low light intensity and
reduced temperature caused a significant decrease in yield (see
radar diagram in Table 1).[25]
Buchwald[18b] and others (Scheme 1B - route IV).[18c-g] 1,3-
Enynes could also be used as radical acceptors to form
substituted allene (1,4-adducts) or alkyne (1,2-adducts)
derivatives.[19] However, catalytic radical carbonyl propargylation
between 1,3-enyne and aldehyde remains an unmet
challenge.[18g]
In recent years, dual catalytic manifolds have emerged as
attractive tools to promote energetically unfavorable reaction
steps and achieve synthetically valuable transformations under
increasingly mild conditions.[20] Since 2018, our group,[21a-b]
Kanai, Mitsunuma and co-workers[21c-d] have independently
achieved allylation of aldehydes using dual photoredox and
chromium catalysis.[21e] Compared to dual nickel/photoredox[20e-j]
or copper/photoredox[20k-n] catalysis, dual chromium/photoredox
catalytic mode is much less explored in synthetic chemistry, but
provides a range of opportunities to achieve challenging radical-
to-polar crossover-based transformations. While alkyl chromium
species could also be generated,[22] propargyl chromium species
have remained out of reach by means of this emerging dual
catalytic system. Considering the paramount importance of NHK
reactions in synthetic chemistry,[3] especially in the realm of total
synthesis of natural products,[3c] we report an alternative way of
generating propargylic radicals[23] using a chromium/photoredox
dual catalytic manifold, achieving the catalytic radical carbonyl
propargylation of aldehydes. The key step towards a successful
process proved to be the selective generation of propargylic
radical III by radical addition to 1,3-enynes, which was trapped
by chromium to form intermediate IV (Scheme 1C). In fact, such
three-component approach would enable rapid increase of
complexity (two bonds formation) compared to the state of the
art (Scheme 1B). Additionally, our strategy features easily
accessible starting materials, tolerant reaction conditions and
thus broad substrate scope.
Table 1. Reaction optimization for radical carbonyl propargylationa
Results and Discussion
Reaction development. In analogy with previous reports from
our group,[21b] we investigated the reaction of 1,3-enyne (1a), 3-
(4-fluorophenyl)propanal (2a) and Hantzsch ester (3a, E1/2
=
1.10 V vs SCE in MeCN)[24] (Table 1). After exploring different
reaction conditions, the best results were accomplished with
CrCl3 (10 mol%), PC-1 (1 mol%, E1/2(*IrIII/IrII) = 1.21 V vs SCE in
MeCN) under irradiation with 450 nm light-emitting diodes (30 W
blue LEDs), affording three-component coupling product 4 in
86% isolated yield with 74:26 dr (entry 1). Interestingly, when
organic photoredox catalyst 4-CzIPN (E1/2(*PC/PC·−) = 1.35 V vs
SCE in MeCN) was employed instead of PC-1, a comparable
yield of 4 was obtained (entry 2). The use of an alternative
Iridium-based photocatalyst PC-2 (E1/2(*IrIII/IrII) = 0.66 V vs SCE
in MeCN) or CrCl2 instead of bench-stable and inexpensive
CrCl3 provided decreased yield (entries 3 and 4). Several
common organic solvents have also been screened, revealing a
moderate (1,4-dioxane and THF) to severe (DMF, acetone)
detrimental influence on the yield of product 4 (entries 5-8).
Predictably, control experiments showed that all the reaction
components were necessary to achieve this radical three-
component carbonyl propargylation coupling (entries 9-11).
Additionally,
a
condition-based
sensitivity
screening
2
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
substituent.[26] We then evaluated the three-component manifold
in the propargylation of a set of different aldehydes (23-37,
Scheme 3, upper), which further corroborated the notion of
functional group tolerance of our protocol. Both acyclic (23) and
cyclic (24-25) aliphatic aldehydes afforded the desired product in
moderate to excellent yields (62-94%), even in the presence of
alkenes (25). Pleasingly, electron-rich aromatics such as indole
(26) and furan (27) were tolerated, despite in the latter case the
lability of the heterocyclic system deemed responsible for the
reduced yield (39%). An array of 3-phenylpropanal derivatives
(28-31) bearing both electron-donating (28, 29) and -withdrawing
(30, 31) groups at different positions of the aromatic ring
delivered the product in good to excellent yields (77-93%).
Further showcasing the compatibility of the protocol with many
functional groups, ranging from halides (32) to polyfluorinated
arenes (33), we explored a set of aldehydes bearing variously
substituted benzamides (32-37), which successfully yielded the
corresponding propargylated products. Furthermore, these
examples were performed employing 4CzIPN instead of PC-1 as
photocatalyst, thus avoiding the use of precious iridium metal.
Additionally, different radical precursors were investigated with
the optimized conditions (38-44, Scheme 3, lower). Notably,
Hantzsch nitriles (3c-h) could be successfully employed in our
dual catalytic system and a variety of homopropargylic alcohols
containing all-carbon quaternary centers (39-44) could be
obtained in good yields. Different scaffolds such as cycloalkyl
(38, 43, 44), aliphatic (39), phenyl (40, 41, 43), naphthyl (42),
and methoxy (41) groups could all be tolerated in this three-
component coupling. Unfortunately, when 4-primary alkyl-1,4-
dihydropyridines ꟷ such as 4-phenethyl-1,4-dihydropyridine ꟷ
were used as radical precursors, the desired product could not
be obtained. According to the recent report by Molander and co-
workers, the corresponding dihydropyridines (DHPs) do not
undergo homolytic C−C cleavage but rather C−H homolysis,
resulting in the formation of 4-alkylated pyridine byproducts.[24e]
Additionally, acyl and carbomoyl radical DHPs sources have
been tested according to the recent reports by Melchiorre and
co-workers,[24f,g] but failed to afford any product under our
standard reaction conditions.
a
Optimization of the reaction conditions: 1a (0.24 mmol, 1.2 equiv.), 2a (0.2
mmol, 1.0 equiv.), 3a (0.4 mmol, 2.0 equiv.), PC-1 (1 mol%), CrCl3 (10 mol%)
in MeCN (1 mL, 0.2 M) at room temperature under irradiation of 30 W blue
LEDs with a cooling fan for 24 hours. b 19F NMR yields were determined using
fluorobenzene as internal standard.
diastereoisomeric ratio of product 4 is 74:26.
c
Yields of isolated product, the
Reaction scope. With these results in hand, we investigated the
generality of our three-component coupling with respect to
different 1,3-enynes (Scheme 2). By varying the tethering length
between the alkyne and phthalimido moiety, the desired
products were obtained in good to excellent yields (4-6) and
comparable levels of diastereoselectivity. Delightfully, the
decrease of the radical precursor 3a excess (see 3.0 mmol scale
reaction) did not significantly impact the yield of product 4,
therefore allowing the minimization of the waste-stream.
Remarkably, the reaction proved suitable for the synthesis of
highly sterically congested quaternary centers (7, 33%) even in
excellent yields (8, 85%). In the former case, free alcohols were
tolerated, thus making the protocol suitable to generate highly
decorated 1,3- (7) or remote diols (17) without the need for
protective groups. In addition to long aliphatic chain derivatives
(9), both tosylamides (10) and the 1,3-enyne synthesized from
the herbicide propyzamide (18) yielded the desired products in
quantitative yield. Benzyl ethers (11), as well as esters (12-14,
16) ranging from trifluoromethyl decorated ones (13, 14) to
simple ethyl derivatives (16) smoothly afforded the desired
coupling products. A variety of aryl ethers containing functional
groups spanning from natural product and drugs such as
estrone (19) and paracetamol (20) derivatives, adamantane (21)
and benzothiazole (22) have been successfully coupled in yields
ranging from 60% (20) to quantitative (19, 21), thus proving the
inertness of enolizable moieties (19, 20) and heterocycles (22).
Finally, these examples (4-22) testify that our protocol is
insensitive towards the alkyne substitution, which could vary
from aryl (7, 15, 16) to α-heteroatom (4, 8, 10, 13, 17-22) and
aliphatic (5, 6, 9, 11, 12, 14). The relative stereochemistry of the
major diastereoisomer was confirmed by single-crystal X-ray
analysis of a suitable specimen of 4, which showed an anti
stereochemistry between the alcohol and the appended isobutyl
3
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
Scheme 2. Scope with respect to 1,3-enynes. a Reaction condition A: 1,3-enyne 1 (0.24 mmol, 1.2 equiv.), aldehyde 2 (0.2 mmol, 1.0 equiv.), 3a (0.4 mmol,
b
2.0 equiv.), PC-1 (1 mol%), CrCl3 (10 mol%) in MeCN (1 mL, 0.2 M) at room temperature under irradiation of 30 W blue LEDs with a cooling fan for 24 hours.
Reaction condition B: Reaction condition A was used, but 4-CzIPN replaced PC-1. c Reaction condition C: aldehyde (0.4 mmol, 2.0 equiv.) and 1,3-enyne (0.2
mmol, 1.0 equiv.) were used under reaction condition A. d Reaction condition B was employed and 3a was reduced (1.5 equiv. instead of 2.0 equiv.).
4
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
Me
EtO2C
Me
Me
CO2Et
Me
R1
OH
R2
R1
PC (1 mol%)
CrCl3 (10 mol%)
O
H
R2
MeCN (0.2 M)
30 W Blue LEDs, RT, 24 h
Me
N
H
Me
1
2
3a
23-37
Aldehydes
Me
OH
OH
OH
OH
O
OH
PhthN
PhthN
Me
5
PhthN
PhthN
N
Me
Me
2
2
Me
Me
Me
Me
Me
Me
26
Me
Me
Me
23
Me
24
Me
25
94%a, 57:43 dr
27
62%a, >95:5 dr
65%a, >95:5 dr
89%a, 72:28 dr
39%a, 70:30 dr (38%b)
b
32
33
34
35
36
37
, R = 2-Cl-(C6H4), 76% , 75:25 dr
OH
OH
O
PhthN
b
a
c
b
BnO
28
29
30
31
4
, R = 3-OMe, 93% , 72:28 dr (52% , 90% )
, R = C6F5, 83% , 80:20 dr
b
a
b
N
R
, R = 4-Ph, 85% , 71:29 dr (42% )
, R = 4-Cl, 77% , 73:27 dr (46%a)
, R = 2,4,6-Me-(C6H2), 75% , 76:24 dr
R
H
Me
Me
b
b
Me
, R = 2-napthyl, 94% , 76:24 dr
a
b
, R = 4-CO2Et, 87% , 71:29 dr
, R = 3-OMe-(C6H4), 86% , 79:21 dr
Me
b
, R = 3-CF3-(C6H4), 84% , 79:21 dr
R1
OH
R2
O
R1
PC
(1 mol%)
R5
CrCl3 (10 mol%)
R3
R4
H
R4
RP
R3
3b-h
MeCN (0.2 M)
30 W Blue LEDs, RT, 24 h
R5
F
1
Radical precursors
2a
38-44
Me
OH
OH
Me
NC
Me
Me
5
PhthN
CN
EtO2C
Me
CO2Et
Me
Me
Me Me
39
F
F
Me
N
H
Me
N
H
38
3b
3c
63%a, > 95:5 dr
53%a, 78:22 dr
X
OH
PhthN
OH
PhthN
Me
Me
Me
Me
F
F
NC
CN
Me
Me Me
NC
CN
Me
Me Me
X
Me
N
H
Me
N
H
a
3d, X = H
3e, X = OMe
40
41
, X = H, 52% , 82:18 dr
42
3f
39%d, 80:20 dr (30%a)
a
, X = OMe, 66% , 82:18 dr
Me
OH
OH
PhthN
PhthN
Me
NC
Me
CN
Me
F
F
NC
Me
CN
Me
N
H
N
H
43
44
3g
3h
63%a, 84:16 dr
42%a, 84:16 dr
Scheme 3. Scope with respect to aldehydes and radical precursors. a Reaction condition A: 1,3-enyne 1 (0.24 mmol, 1.2 equiv.), aldehyde 2 (0.2 mmol, 1.0
equiv.), radical precursor 3 (0.4 mmol, 2.0 equiv.), PC-1 (1 mol%), CrCl3 (10 mol%) in MeCN (1 mL, 0.2 M) at room temperature under irradiation of 30 W blue
LEDs with a cooling fan for 24 hours. b Reaction condition B: 4-CzIPN was used instead of PC-1. c Reaction condition C: aldehyde (0.4 mmol, 2.0 equiv.) and
5
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
d
1,3-enyne (0.2 mmol, 1.0 equiv.) under reaction condition A. Reaction condition D：Reaction condition A was employed and MeCN (1.0 mL, 0.2 M) was
replaced with MeCN:DMF 2:1 (1.2 mL 0.17 M).
Applications and Preliminary Mechanistic Investigation. Our
methodology towards homopropargylic alcohols offers
visible (Scheme 4E) and Stern-Volmer experiments (see
supporting information for details) were performed and the
results clearly show that only the photoredox catalyst (either PC-
1 or 4-CzIPN) absorbs visible light in the reaction system and
the photoluminescence can be quenched exclusively by
Hantzsch ester 3a. Based upon these preliminary mechanistic
results and our previous study,[21b] we propose that alkyl radical
VII is generated from a suitable radical precursor following
reductive quenching of the photoexcited PC-1 or 4-CzIPN
(Scheme 4F). Then the LnCr(III) species is reduced in situ to
LnCr(II) (E1/2 = −0.65 V vs SCE in H2O, E1/2 = −0.51 V vs SCE in
DMF)[77] by the reduced photocatalyst PC·− (for instance, organic
dye 4CzIPN, E1/2 (PC/PC·−) = −1.21 V vs SCE in MeCN;[29] PC-1,
E1/2(IrII/IrIII) = −1.37 V vs SCE in MeCN[30]). The alkyl radical VII
could either reversibly add to a low-valent LnCr(II) species to
form the resting state Cr(III)-alkyl complex VIII or add to 1,3-
enynes to generate a propargylic radical in equilibrium with its
allenyl equivalent. After radical capture by the LnCr(II) species,
propargylic Cr(III) intermediate IV and allenic species Cr(III) IV’
are generated. Interestingly, when attempting to obtain
macrocyclic alcohols using a designed 1,3-enyne containing an
aldehyde functional group in the end through cascade reaction
by dual chromium/photoredox catalysis, no macrocyclization
could be observed. Instead, we obtained a mixture of acyclic
alkyne and allene radical addition products, which suggest the
existence of intermediates IV and IV’ (see supporting
information for details). Finally, either IV or IV’ can react with
suitable aldehydes 2 to yield the final homopropargylic products
(4-44) through an anti-transition state, which accounts for the
observed diastereoselectivity. The reduced diastereoselectivity
of the process upon reacting polysubstituted enynes (8, 57:43
dr) can be tentatively ascribed to the lowered energetic
difference between the anti- and syn-transition states due to
increased steric demand of the substituents (see supporting
information for details).
a
straightforward platform to access motifs such as
homopropargylic ketones and propargylated amines, which are
key motifs in many drugs (e.g. Oxybutynin and oxotremorine).
Delightfully, homopropargylic ketone 45 could be obtained in
87% yield through this three-component coupling reaction and
sequential simple oxidation in one step. Additionally, the free
propargylic amine product 46 could be obtained in 64% yield
through the straightforward Ing-Manske procedure, without the
need of chromatographic purification (Scheme 4A). We
envisaged that homopropargylic alcohols can offer a gateway
towards α-allenyl ketones and alcohols, which are highly
prevalent scaffolds in carotinoids and terpenoids natural
products (e.g. Mimulaxanthin or Icariside B1).[27] Indeed,
straightforward oxidation-isomerization sequence delivered the
allene 47 in high yield, thus testifying the feasibility of our
protocol towards its utilization in synthetic endeavors. To shed
light
on
the
possible
reaction
mechanism,
cyclopropanecarboxaldehyde (2s) was subjected to the
optimized reaction conditions, product 48 was obtained in good
yield and no cyclopropane ring opening was observed, speaking
against the intermediacy of ketyl radical intermediates in the
coupling process, in addition to unfavorable redox potentials
(Scheme 4B).[28] Additionally, the radical scavenger TEMPO (2
equivalents) was added to the standard reaction, causing the
disturbance of the catalytic manifold (desired product 20 could
not be detected), while iPr-TEMPO adduct 49 was detected
(Scheme 4C). This suggests that the reaction may proceed
through a radical-based mechanism. We also synthesized 1,3-
enyne 1t containing a three membered ring, which delivered ꟷ
under the optimized conditions ꟷ a mixture of ring-opening
products arising from intermediate V collapsing toward radical
intermediate VI (Scheme 4D), therefore unequivocally
suggesting the intermediacy of propargyl radicals. Finally, UV-
6
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
Scheme 4. Preliminary Mechanistic Investigation. A. Synthetic application; B. Radical probing experiment I; C. Radical inhibitor experiment; D. Radical probing
experiment II; E. UV-Vis spectra. Reaction mixture refers to Table 1 – entry 2; F. Proposed mechanism. DMP = Dess-Martin Periodinane; TEMPO = (2,2,6,6-
Tetramethylpiperidin-1-yl)oxyl.
crossover mechanism through the intermediacy of either
propargyl- or allenyl-Cr(III) species. We anticipate that this
strategy along with other reports will serve as an innovative
multi-component reaction and will inspire chemists to revisit the
Conclusion
synthetic potential of organochromium chemistry.
In summary, we have demonstrated for the first time a mild and
scalable radical carbonyl propargylation via dual
chromium/photoredox catalysis with excellent functional group
tolerance. This redox-neutral method provides an alternative
strategy to carbonyl propargylation chemistry, enabling the
generation of a library of homopropargylic alcohols bearing
highly congested structures in good to excellent yields.
Preliminary mechanistic studies are suggestive of a radical-polar
Acknowledgements
This work was generously supported by the Alexander von
Humboldt
Foundation
(H.-M.H.)
and
the
Deutsche
7
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10.1002/anie.202011996
Angewandte Chemie International Edition
RESEARCH ARTICLE
Forschungsgemeinschaft (Leibniz Award, SBF 858). We also
thank Luca Schwarz, Frederik Sandfort and Dr. Jun Li (all
University of Münster) for helpful discussions.
[16] a) R. L. Patman, V. M. Williams, J. F. Bower, M. J. Krische, Angew.
Chem. Int. Ed. 2008, 47, 5220–5223; Angew. Chem. 2008, 120, 5298–
5301 b) L. M. Geary, S. K. Woo, J. C. Leung, M. J. Krische, Angew.
Chem. Int. Ed. 2012, 51, 2972–2976; Angew. Chem. 2012, 124, 3026–
3030; c) K. D. Nguyen, D. Herkommer, M. J. Krische, J. Am. Chem.
Soc. 2016, 138, 5238–5241.
Conflict of interest
The authors declare no conflict of interest.
[17] Y. Mori, G. Onodera, M. Kimura, Chem. Lett. 2014, 43, 97–99.
[18] a) F. Meng, F. Haeffner, A. H. Hoveyda, J. Am. Chem. Soc. 2014, 136,
11304–11307; b) Y. Yang, I. B. Perry, G. Lu, P. Liu, S. L. Buchwald,
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Perry, D. J. Procter, Angew. Chem. Int. Ed. 2020, 59, 4879–4882;
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Gan, L. Yin, Org. Lett. 2019, 21, 931–936; f) X.-C. Gan, Q. Zhang, X.-S.
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Keywords: radical-polar • carbonyl • propargylation • dual
catalysis • chromium
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RESEARCH ARTICLE
Entry for the Table of Contents
Herein, we report for the first time the radical three-component carbonyl propargylation between 1,3-enynes, aldehydes and suitable
radical precursors via dual chromium/photoredox catalysis. This redox-neutral reaction occurs under very mild conditions, shows high
functional group tolerance and represents a complementary novel approach for preparing valuable synthetic architectures from
simple chemicals.
Institute and/or researcher Twitter usernames: @GloriusGroup
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