Mild, Redox-Neutral Formylation of Aryl Chlorides through the Photocatalytic Generation of Chlorine Radicals

Article abstract of DOI:10.1002/anie.201702079

We report a redox-neutral formylation of aryl chlorides that proceeds through selective 2-functionalization of 1,3-dioxolane through nickel and photoredox catalysis. This scalable benchtop approach provides a distinct advantage over traditional reductive carbonylation in that no carbon monoxide, pressurized gas, or stoichiometric reductant is employed. The mild conditions give unprecedented scope from abundant and complex aryl chloride starting materials.

Full text of DOI:10.1002/anie.201702079

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Mild, Redox-Neutral Formylation of Aryl Chlorides via
Photocatalytic Generation of Chlorine Radicals
Authors: Matthew K. Nielsen, Benjamin J. Shields, Junyi Liu, Michael J.
Williams, Michael J. Zacuto, and Abigail Gutmann Doyle
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201702079
Angew. Chem. 10.1002/ange.201702079
Link to VoR: http://dx.doi.org/10.1002/anie.201702079
http://dx.doi.org/10.1002/ange.201702079

10.1002/anie.201702079
Angewandte Chemie International Edition
COMMUNICATION
Mild, Redox-Neutral Formylation of Aryl Chlorides via
Photocatalytic Generation of Chlorine Radicals
Matthew K. Nielsen[a][+], Benjamin J. Shields[a][+], Junyi Liu[a], Michael J. Williams[b], Michael J. Zacuto[b]
and Abigail G. Doyle*[a]
Abstract: We report a redox-neutral formylation of aryl chlorides that
Existing Strategies for Aryl Formylation
A
proceeds through selective 2-functionalization of 1,3-dioxolane via
nickel and photoredox catalysis. This scalable, benchtop approach
provides a distinct advantage over traditional reductive carbonylation
in that no carbon monoxide, pressurized gas, or stoichiometric
reductant is employed. Mild conditions enable unprecedented scope
from abundant and complex aryl chloride starting materials.
Aromatic Substitution
Reductive Formylation
Organometallic
Addition
O
CHO
"
"
O
O
H2/CO
DMF
H
M
X
Ar
Ar
Ar
H
Ar
H
OHC
M = Li, MgX
X = Br, I
EDG
EDG
high T & P,
stoich. reductant
harsh organometallic
reagents, cryogenic T
SEAr reactivity &
selectivity
Aromatic aldehydes are among the most versatile
intermediates in the synthesis of pharmaceuticals, fragrances,
fine chemicals, and natural products.[1] Indeed, the functional
group can be rapidly elaborated via an ever growing host of C–C
and C–X bond-forming reactions. Despite the ubiquitous
application of aryl aldehydes, synthetic methods for their
preparation are limited. Classical approaches such as the
Vilsmeier–Haack and Duff reactions proceed via electrophilic
Redox-Neutral C–H Functionalization Approach
B
hυ
room temperature
broad FG tolerance
Cl
Ir, Ni
R H
Ar
Ar
R
Ar Cl
NiIII
user friendly and scalable
hυ
O
O
O
Cl
Ar
O
O
H
Ar
Ar
H
[hetero]aryl
chloride
inexpensive formyl
equivalent
[hetero]aryl
acetal
[hetero]aryl
aldehyde
aromatic
substitution;
therefore
their
reactivity
and
regioselectivity are endogenous to the particular aryl substrate
(Figure 1A).[2] As an alternative, traditional organometallic
methods, such as the addition of Grignard reagents to DMF at
cryogenic temperatures, impart regiocontrol at the expense of
functional group compatibility.[3] To date, the most general
method for the synthesis of aryl aldehydes is palladium
catalyzed reductive carbonylation of aryl iodides and bromides,
first reported by Heck in 1974 under 100 atm of syngas (1:1
H2:CO) at 150 °C.[4] Although this procedure has been
performed on multi-ton scale,[5] the conditions are not ideal for
benchtop synthesis due to the hazards associated with carbon
monoxide and the specialized equipment required for handling
high pressure syngas. To develop user-friendly protocols,
several laboratories have reported alternative condensed phase
reductants[6] and CO surrogates[7] such as the crystalline
N-formylsaccharin.[7b] Nevertheless, reductive formylations are
still limited to simple arenes due to the general requirements of
high reaction temperatures and stoichiometric reducing agents.
Moreover, most methods are incapable of employing aryl
chlorides,[8] by far the most abundant and diverse class of aryl
halides.[9]
Figure 1. (a) Prior art in aryl formylation. (b) Proposed redox-neutral
formylation of aryl chlorides via C–H activation of 1,3-dioxolane.
arylations at room temperature. In contrast to systems reported
by MacMillan[11] and Molander[12], which primarily employ aryl
bromides and iodides, our method utilizes aryl chlorides by
design. Here we demonstrate that this manifold can be
leveraged to enable redox-neutral formylation by selective 2-
arylation of the inexpensive and abundant solvent 1,3-dioxolane
with aryl chlorides followed by a mild acidic workup (Figure 1B).
Importantly this strategy overcomes the challenges of positional
selectivity and functional group compatibility associated with
classical formylation reactions and obviates the need for
gaseous reagents, stoichiometric reductants and high reaction
temperatures required for reductive carbonylation.
We envisioned that oxidative addition of Ni(0) (Figure 2, 1)
into an aryl chloride would produce Ni(II) intermediate 2.
Simultaneously, visible light irradiation of Ir(III) photocatalyst 3
would generate triplet excited *Ir(III) (τ0 = 2.3 µs, *E1/2 = 1.21 V
vs SCE in MeCN) (4) which could engage 2 (EP = 0.85 V vs SCE
in THF) in photoinduced electron transfer to give presumed
Ni(III) intermediate 5.[10,13] According to our prior studies,[10]
photolysis of 5 produces Ni(II) species 6 and a chlorine radical,
capable of abstracting a hydrogen atom from 1,3-dioxolane. A
concern in developing this reaction was that 1,3-dioxolane has
two sets of chemically distinct α-oxy C–H bonds.
Thermodynamic computations imply a moderate driving force for
2-functionalization (ΔBDFE = 1.4 kcal mol-1), which we expected
could be influenced by the Ni catalyst that accepts the resultant
Recently, our lab[10] and others reported directing group free
Csp3–H cross-coupling platforms capable of carrying out C–H
[a]
M. K. Nielsen,[+] B. J. Shields,[+] J. Liu, Prof. A. G. Doyle
Department of Chemistry, Princeton University
120 Washington Road, Princeton, NJ 08544 (USA)
E-mail: agdoyle@princeton.edu
[b]
[+]
Dr. M. J. Williams, Dr. M. J. Zacuto
Drug Substance Development, Celgene Corporation
556 Morris Ave., Summit, New Jersey 07901, (USA)
Email: mzacuto@celgene.com
These authors contributed equally to this work.
carbon-centered radical.
Reductive elimination from Ni(III)
species 7 would then give the aryl-dioxolane acetal and
hydrolytic workup would furnish the desired aryl aldehyde
product. Finally, to close both cycles Ni(I) species 8
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201702079
Angewandte Chemie International Edition
COMMUNICATION
(E1/2[Ni(II)/(0)] = −1.2 V vs SCE in DMF) can be reduced by Ir(II)
species 9 (E1/2 = −1.37 V vs SCE in MeCN).[13,14]
Ar
aryl chloride
Cl
LnNi0
O
1
O
Cl
LnNiII Ar
2
We began studying the proposed formylation reaction with
emphasis on the development of a user friendly and scalable
Ar
IrII
9
SET
aryl acetal
reductant
protocol. We were pleased to find that the commercial, bench-
[15]
LnNiI 8
stable precatalyst systems—Ir[dF(CF3)ppy]2(dtbbpy)PF6
and
IrIII
3
NiCl2·DME with 4,4'-di-t-butyl-2,2'-bipyridine ligand (dtbbpy)—
SET
combined with two equivalents of potassium phosphate under
*IrIII
oxidant
4
irradiation
with
blue
LEDs
enabled
the
selective
Haq
Workup
2-functionalization of 1,3-dioxolane with numerous aryl chlorides.
A subsequent mild acidic workup gave the desired aryl (Figure 3,
10–18), heteroaryl (19–22) and biologically relevant (23–34)
aldehydes in good to excellent yields with minimal loss of
material upon acetal hydrolysis (76% yield 10 vs. 74% yield 11).
Interestingly, the average selectivity for the cross-coupling step
favoured methylene over ethylene C–H functionalization by 9:1.
This observation is in qualitative agreement with computed C–H
BDFEs, which predict a selectivity of 5:1 purely based on
thermodynamics and stoichiometry. However, the disparity
suggests that other factors such as polar effects in the rebound
O
O
hυ
Cl
7
5
LnNiIII
Ar
hυ
LnNiIII
Ar
O
O
Cl
6
O
LnNiII Ar
LnNiII Ar
BDFE
kcal mol-1
Ar
H
O
aryl aldehyde
a
b
86.8
88.2
H
H
O
HCl
a
b
Figure 2. Proposed catalytic cycle.
O
Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%)
NiCl2•DME (10 mol%)
dtbbpy (15 mol%)
Cl
O
O
1M HCl
H
O
parent compound
yield
H
H
O
acetone, 23 °C
K3PO4 (2 eq), 0.05 M
34 W Blue LED, 72 h, 23 °C
dioxolane
(solvent)
[hetero]aryl
aldehyde
[hetero]aryl
chloride
not isolated
Aryl Chlorides
Pharmaceutical and Biological Compounds
O
O
O
O
O
O
Me
O
O
H
H
O
H
H
H
O
O
O
Me
O
H
S
t-Bu
t-Bu
NC
Me Me
N
O
O
N
Me
O
10: 76% yield[a]
11: 74% yield
12: 83% yield
O
Me
Me
(±)-chlormezanone
23: 89% yield
fenofibrate
24: 81% yield
procymidone
25: 51% yield
O
O
O
N
O
O
H
H
H2N
O
H
N
H
HO
N
H
H
MeO
Me
O
O
O
Me
N
HO
Me
N
H
13: 58% yield
S
NH
14: 64% yield
15: 71% yield
Me Me
O
(±)-cyproconazole
26: 66% yield[d]
(±)-hexythiazox
28: 67% yield
monalide
27: 66% yield
Me
N
O
O
O
O
O
N
Cbz
O
O
H
Me
N
O
Me
NH
EtO
H
H
N
H
H
Ph
N
H
O
O
NH
OH
H
N
CN
CN
Cbz
OBn
N
N
H
16: 75% yield[b]
17: 59% yield[b]
18: 59% yield
OH
O
O
O
OBn
DL-4-chlorophenylalanine
29: 65% yield
Ala-Ser-Phe(3-Cl)
30: 56% yield
loratadine
31: 76% yield
Heteroaryl Chlorides
O
Ph
Ph
O
O
O
O
O
O
Me
N
O
N
H
OAc
H
H
BnO
O
N
AcO
Me
O
H
N
O
N
Me
O
O
OAc
N
Me
N
N
AcO
S
O
CN
O
Me
CF3
zomepirac
33: 74% yield
diazepam
32: 73% yield
salmon-gal
34: 38% yield
20: 71% yield[c] 21: 73% yield[c] 22: 78% yield[c]
19: 70% yield
Figure 3. Formylation of aryl chlorides: substrate scope. Yields are an average of two runs on 0.25 mmol scale. For 23 – 34, the name of the parent compound is
listed. [a]Acid hydrolysis omitted. [b]Benctop setup; single run. [c]Aldehyde does not form under hydrolysis conditions. [d]2.3:1 dr (conserved from starting material).
This article is protected by copyright. All rights reserved.

10.1002/anie.201702079
Angewandte Chemie International Edition
COMMUNICATION
of the radical to Ni(II) may also be important. Based on these
observations, it is noteworthy that the reaction of chlormezanone
afforded 23 in 89% yield—the maximum theoretical yield based
on average selectivity. For most substrates, simple silica gel
column chromatography was sufficient to obtain the desired
product in high purity (see SI for details). However, in some
cases, a mixture of aryl aldehyde and isomeric acetal resulting
from 4-functionalization of dioxolane was isolated. Notably,
regioisomerism can be avoided by employing 1,3,5-trioxane as a
formyl source; for example, using 50 equivalents of 1,3,5-
trioxane and benzene as a solvent, the trioxanyl acetal of 12 can
be prepared in 57% yield under otherwise identical conditions.
Control reactions demonstrated that in the absence of light,
nickel or photoredox catalyst, no product was formed. Reactions
carried out on the benchtop afforded comparable yields to those
set up in a glovebox; for example, 23 was obtained in 81% yield
(vs 89% yield) using Schlenk technique. In addition, the reaction
is amenable to operationally simple batch scale-up; fenofibrate
gave 1.47 g of 24 in 83% yield on 5 mmol scale. Moreover,
benchtop scale-up reactions of 16 and 17 gave 64% yield and
70% yield respectively on gram scale.
current trends in synthesis in which aryl aldehydes are employed
early in a synthetic sequence.[1a,1b]
We recognized that in some instances it may be
advantageous to employ aryl bromides or iodides in this
transformation. 4-Bromobenzonitrile and 4-bromobiphenyl
performed modestly well in the coupling reaction, giving the
corresponding aryl acetals (36-CN and 36-Ph) in 52% and 36%
yield respectively (Figure 4). Notably, aryl bromides are
significantly more selective for 2-functionalization, in both cases
doubling the regioisomeric ratio. This observation is consistent
Figure 4. Aryl halide selectivity studies. Yields determined by GC-FID using 1-
fluoronaphthalene as an external standard. See Tables S2 and S3 for
additional experiments and reaction conditions. [a] With addition of 1 equiv
TBACl.
Reaction scope investigations indicate that the method is
general across a broad range of electronically differentiated aryl
chlorides. It was observed that electron-deficient aryl chlorides
generally afforded higher yields than electron-rich substrates
over the 72 hour reaction time. Time point experiments showed
that while the reaction of 4-chlorobenzonitrile reached nearly full
conversion within 48 hours, 4-chloroanisole continued to
undergo cross coupling for the duration of the 96 hour
monitoring period (Figure S5), indicating electron-rich substrates
react at a reduced rate. Sterically encumbered chloroarenes
bearing ortho substituents underwent coupling to give the
corresponding formylated products (17, 21). Additionally, the
with a halogen radical abstraction mechanism wherein selectivity
for the initial C–H functionalization is governed by Hammond’s
postulate—that is, the late transition state in bromine abstraction
(BDEH–Br = 88 kcal·mol−1 vs. BDEH–Cl = 103 kcal·mol−1) results in
higher selectivity for the thermodynamically favored alkyl radical
product. Interestingly, the change in selectivity for each set of
aryl chlorides and aryl bromides was moderately substituent
dependent (Entry 1: Entry 4 = 1:1.3, Entry 2: Entry 5 = 1:1.1), in
agreement with the proposed role of aryl Ni(II) (Figure 2, species
6) in the radical rebound step. Together these observations
suggest the potential for both halide- and substrate-control over
C–H functionalization selectivity. Although aryl iodides alone are
incompetent (BDEH–I = 71 kcal·mol−1), moderate yield can be
attained through halide exchange with tetrabutylammonium
chloride (TBACl).
dichloride
fungicide
procymidone
underwent
multiple
functionalizations to form dialdehyde 25.
A broad range of reactive functional groups were well
tolerated, highlighting the exceptionally mild reaction conditions.
Aryl chlorides containing protic functionality underwent efficient
formylation to yield primary alcohols 14 and 30, primary and
tertiary benzylic alcohols 18 and 26, primary amide 15 and
secondary amides 27–30. Functional groups susceptible to
hydrogenation under typical reductive carbonylation conditions
can be accommodated, such as alkene 31 and imine 32.
Furthermore, formylation proceeds in the presence of diverse
heterocycles, both distal and proximal, including pyridines 16, 17,
20, 21, and 31, pyrazole 18, benzothiazole 19, quinoline 22,
triazole 26, thiazolidinone 28, benzodiazepine 32, pyrrole 33,
and indole 34. We were pleased to find that numerous
pharmaceuticals (23, 24, 31–33) and agrochemicals (25–28)
were accommodated. Formylations that yielded amino ester 29,
tripeptide 30, and glycoside 34 are particularly noteworthy,
demonstrating a new strategy for synthesizing biomolecular
In a preliminary evaluation of other substrate classes under
unoptimized conditions, alkyl bromide (3-bromopropyl)benzene
afforded 4-phenylbutanal in 6% yield, demonstrating the
potential of this strategy to convert alkyl halides to homologated
aldehydes. Moreover, the acyl chloride 4-methylbenzoyl chloride
underwent coupling to give the corresponding protected glyoxal
in 39% yield (See SI for details). By comparison, under reductive
carbonylation conditions, acid halides are protodehalogenated to
form aldehydes,[4] and the aryl glyoxals are typically only
accessible through oxidative methods.
Although various oxidation states (ie. alcohol, carboxylic acid
derivative) can be accessed from aldehydes, redox
manipulations are not ideal for step economy and require
stoichiometric oxidants or reductants. We recognized the
generality of the redox-neutral Csp3–H functionalization strategy
underlying our formylation reaction and hypothesized that direct
aldehydes,
a desirable functional handle in the field of
bioconjugation.[16] More generally, the unparalleled scope of this
transformation offers the possibility for late-stage formylation of
typically inert aryl chlorides and thus the potential to disrupt
This article is protected by copyright. All rights reserved.

10.1002/anie.201702079
Angewandte Chemie International Edition
COMMUNICATION
3718–3721. c) G. Fráter, J. A. Bajgrowicz, P. Kraft Tetrahedron 1998,
54, 7633–7703. d) R. B. Woodward, M. P. Cava, W. D. Ollis, A. Hunger,
H. U. Daeniker, K. Schenker J. Am. Chem. Soc. 1954, 76, 4749–4751.
e) P. Magnus, N. Sane, B. P. Fauber, V. Lynch J. Am. Chem. Soc.
2009, 131, 16045–16047.
access to other oxidation states could be afforded by judicious
selection of C–H coupling partner. Gratifyingly, under
unoptimized conditions the methyl ester and benzyl alcohol of 4-
chlorobiphenyl could be accessed by direct arylation of trimethyl
orthoformate, via a tertiary radical intermediate, and trimethyl
orthoacetate to give 39 and 40 in 14% and 42% yield
respectively (Figure 5). These preliminary examples provided
promising results for further development.
[2]
a) K. Reimer, F. Tiemann Ber. Dtsch. Chem. Ges. 1876, 9, 1268–1278.
b) L. Gattermann, J. A. Koch Chem. Ber. 1897, 30, 1622–1624. c) L.
attermann, W. Berchelmann Ber. Dtsch. Chem. Ges. 1898, 31, 1765–
1769. d) A. Vilsmeier, A. Haack Chem. Ber. 1927, 60, 119–122. e) J. C.
Duff, E. J. Bills J. Chem. Soc. 1932, 1987–1988.
O
Cl
[3]
[4]
[5]
L. Bouveault Bull. Soc. Chim. Fr. 1904, 31, 1306–1322.
O
38
75% yield
H
A. Schoenberg, R. F. Heck J. Am. Chem. Soc. 1974, 96, 7761–7764.
S. Klaus, H. Neumann, A. Zapf, D. Strübing, S. Hübner, J. Almena, T.
Riermeier, P. Groß, M. Sarich, W.-R. Krahnert, K. Rossen, M. Beller
Angew. Chem., Int. Ed. 2006, 45, 154–158. Angew. Chem. 2006, 118,
161–165.
O
H
Ph
Ph
Ph
Ph
O
Cl
Cl
OMe
39[a]
14% yield
OMe
MeO
OMe
[6]
[7]
a) V. P. Baillargeon, J. K. Stille J. Am. Chem. Soc. 1983, 105, 7175–
7176. b) I. Pri-Bar, O. Buchman J. Org. Chem. 1984, 49, 4009–4011.
a) T. Okano, N. Harada J. Kiji Bull. Chem. Soc. Jpn. 1994, 67, 2329–
2332. b) T. Ueda, H. Konishi, K. Manabe Angew. Chem., Int. Ed. 2013,
52, 8611–8615. Angew. Chem. 2013, 125, 8773–8777. c) B. Yu, Y.
Zhao, H. Zhang, J. Xu, L. Hao, X. Gao, Z. Liu Chem. Commun. 2014,
50, 2330–2333. d) X. Jiang, J.-M. Wang, Y. Zhang, Z. Chen, Y.-M. Zhu,
S.-J. Ji Org. Lett. 2014, 16, 3492–3495. e) K. Natte, A. Dumrath, H.
Neumann, M. Beller Angew. Chem., Int. Ed. 2014, 53, 10090–10094.
Angew. Chem. 2014, 126, 10254–10258. f) N. Iranpoor, H. Firouzabadi,
E. Etemadi-Davan, A. Rostami, K. R. Moghadam Appl. Organometal.
Chem. 2015, 29, 719–724.
H
tertiary radical
functionalization
OH
OMe
40
42% yield
MeO
O
H
Ph
Me
Ph
Figure 5. Direct access to formyl oxidation and reduction analogues via redox-
neutral Csp3–H functionalization. Isolated yields. [a] Generates methoxy
functionalization product in 15% yield. See SI for experimental details.
[8]
[9]
Y. Ben-David, M. Portnoy, D. Milstein J. Am. Chem. Soc. 1989, 111,
8742–8744.
In conclusion, we have demonstrated a redox-neutral C–H
functionalization approach to aryl formylation which proceeds
under exceptionally mild conditions to give numerous aryl,
heteroaryl, and biologically relevant aldehydes.
A Ni/photoredox decarboxylative approach for formylating activated aryl
chlorides was recently reported. H. Huang, X. Li, C. Yu, Y. Zhang, P.
Mariano, W. Wang Angew. Chem., Int. Ed. 2017, 56, 1500–1505.
Angew. Chem. 2017, 129, 1522–1527.
[10] B. J. Shields, A. G. Doyle J. Am. Chem. Soc. 2016, 138, 12719–12722.
[11] M. H. Shaw, V. W. Shurtleff, J. A. Terrett, J. D. Cuthbertson, D. W. C.
MacMillan Science 2016, 352, 1304–1308.
Acknowledgements
[12] D. R. Heitz, J. C. Tellis, G. A. Molander J. Am. Chem. Soc. 2016, 138,
12715–12718.
Financial support was provided by NIGMS (R01 GM100985) and
Celgene Corporation.
[13] M. S. Lowry, J. I. Goldsmith, J. D. Slinker, R. Rohl, R. A. Pascal, G. G.
Malliaras S. Bernhard Chem. Mater. 2005, 17, 5712–5719.
[14] M. Durandetti, M. Devaud, J. Perichon New J. Chem. 1996, 20, 659–
667.
Keywords: formylation • nickel • C–H functionalization • radical
photoelimination
[15] (4,4'-Di-t-butyl-2,2'-bipyridine)bis[3,5-difluoro-2-[5-trifluoromethyl-2-
pyridinyl-κN)phenyl-κC]iridium(III) hexafluorophosphate [870987-63-6].
[16] I. S. Carrico, B. L. Carlson, C. R. Bertozzi, Nat. Chem. Biol. 2007, 3,
321–322.
[1]
a) K. L. Baumann, D. E. Butler, C. F. Deering, K. E. Mennen, A. Millar,
T. N. Nanninga, C. W. Palmer, B. D. Roth Tetrahedron Lett. 1992, 33,
2283–2284. b) J. M. McNamara, J. L. Leazer, M. Bhupathy, J. S. Amato,
R. A. Reamer, P. J. Reider, E. J. J. Grabowski J. Org. Chem. 1989, 54,
This article is protected by copyright. All rights reserved.

10.1002/anie.201702079
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
M. K. Nielsen, B. J. Shields, J. Liu, M. J.
Williams, M. J. Zacuto, A. G. Doyle*
Page No. – Page No.
Mild,
Redox-Neutral
Formylation of Aryl Chlorides
via Photocatalytic Generation
of Chlorine Radicals
Cbz
NH
O
Me
O
hυ hυ
H
NH
O
O
H
N
Cl
Ni Ir
Ar
H
Ar
H
O
OH
O
O
OBn
• no CO or reductant • mild conditions • broad scope
25 examples
up to 89% yield
Aromatic aldehydes are generated from abundant aryl chlorides via nickel-photocatalyzed C–H functionalization of the inexpensive
solvent 1,3-dioxolane. The absence of pressurized carbon monoxide and a stoichiometric reductant enables broad functional group
tolerance and scope.
This article is protected by copyright. All rights reserved.