Synthesis of Aldehydes by Organocatalytic Formylation Reactions of Boronic Acids with Glyoxylic Acid

Article abstract of DOI:10.1002/anie.201703127

Reported herein is a conceptually novel organocatalytic strategy for the formylation of boronic acids. New reactivity is engineered into the α-amino-acid-forming Petasis reaction occurring between aryl boronic acids, amines, and glyoxylic acids to prepare aldehydes. The operational simplicity of the process and its ability to generate structurally diverse and valued aryl, heteroaryl, and α,β-unsaturated aldehydes containing a wide array of functional groups, demonstrates the practical utility of the new synthetic strategy.

Full text of DOI:10.1002/anie.201703127

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Synthesis of Aldehydes by Organocatalytic Formylation
Reactions of Boronic Acids with Glyoxylic Acid
Authors: Wei Wang, He Huang, Chenguang Yu, Xiangmin Li,
Yongqiang Zhang, Yueteng Zhang, Xiaobei Chen, Patrick S.
Mariano, and Hexin Xie
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.201703127
Angew. Chem. 10.1002/ange.201703127
Link to VoR: http://dx.doi.org/10.1002/anie.201703127
http://dx.doi.org/10.1002/ange.201703127

10.1002/anie.201703127
Angewandte Chemie International Edition
DOI: 10.1002/anie.200((will be filled in by the editorial staff))
Organocatalysis
Synthesis of Aldehydes by Organocatalytic Formylation Reactions of
Boronic Acids with Glyoxylic Acid**
He Huang,[a] Chenguang Yu,[a] Xiangmin Li,[a,b] Yongqiang Zhang,[b] Yueteng Zhang,[a] Xiaobei
Chen,[b] Patrick S. Mariano,[a]* Hexin Xie,[b]* and Wei Wang[a,b]
*
Abstract: We report a conceptually novel organocatalytic strategy
for formylation of boronic acids, in which a new reactivity is
engineered into the α-amino acid forming Petasis reaction
occurring between aryl boron acids, amines and glyoxylic acid. The
feasibility and preparative power of the protocol was demonstrated
by its use to prepare aldehydes from broadly accessible aryl and
alkenyl boronic acids, glyoxylic acid, and the cheap N-alkylaniline
derivatives, tetrahydroquinoline and indoline, as catalysts.
Furthermore, the operational simplicity of the process, which is
performed by simply mixing these reagents under ambient
conditions, and its ability to generate structurally diverse and
valued aryl, heteroaryl and α,β-unsaturated aldehydes containing a
wide array of functional groups, demonstrates the practical utility of
the newly unveiled synthetic strategy.
compatible with substances possessing acid and base sensitive
functional groups. Finally, control of the regiochemical courses of
these reactions makes it difficult to introduce aldehyde functionality
at desired positions. Because of these limitations, the development
of protocols for introduction of the aldehyde functional group in a
selective and predictable manner, and with a high functional group
tolerance remains a key challenge in preparative organic chemistry.
A. Well established transition metal complexes catalyzed functionalization of boronic acids
B(OH)2
NO2, N3, NH2
oxidation or
halodeboronation
O, F, Cl, Br, I
amination
X
transition metal
complexes
X
transition metal
complexes
X
or heteroaryl
transition metal
complexes
cross couplings
alkyl, alkynyl, alkenyl and alkyl
W
ith more than four thousand being commercially available, aryl
X
boronic acids are one of the most versatile building blocks in
organic synthesis.[1] Notably, recent significant advance in
borylation methods has made aryl boronic acids, particularly those
that are heavily functionalized, more readily accessible.[2] The
unique reactivity of substances in this family has led to a myriad of
carbon-carbon and carbon-heteroatom bond forming processes,
which are difficult to carry out or show poor functional group
tolerance and/or low efficiency when their halide counterparts are
employed as substrates. These reactions, which include the
introduction of oxygen,[3] nitrogen,[4] halogen,[5] and alkyl, alkynyl,
alkenyl and alkyl moieties,[6] are generally accomplished using
transition metal complexes (Scheme 1A). However, to the best of
our knowledge, no examples of catalytic formylation reactions of
arylboronic acids exist.
Aldehydes occupy a unique position in organic chemistry owing
to the versatility of the aldehyde group, which is capable of
undergoing various transformations.[7] Classical methods[8] for
aldehyde synthesis generally require large amounts of reagents and
multi-step sequences, and they often result in the production of at
least stoichiometric amounts of byproducts. Furthermore, the harsh
reaction conditions needed for these processes are often not
B. This work: the first organocatalytic formylation of boronic acids
RR'NH
as reagent
Ar'NHR 3
as catalyst
R
R'
O
N
+ CHO
CO2H H2O
ArB(OH)2
Petasis
reaction
this work Ar
H
Ar
2
CO2H
1
4
O
O
Ar'NHR
Ar
H
3
H
CO2H
4
2
N
H
H2O
3a
R N-Ar'
R N-Ar'
C
N
H
C
Ar
H
3b
H
CO2H
7
5
H
CO2 + H+ + HO2
R
Ar'
N
SET
ArB(OH)2
C
H
-
Ar
CO2
1
H2O2
O2
6
Scheme 1. Functionalization of versatile boronic acids and
formylation reactions
The state-of-the-art methods for the synthesis of synthetically
important aldehydes, such as palladium catalyzed formylation
reactions of aryl halides with CO/H2, pioneered by Heck,[9] mainly
rely on precious transition metals. While significant advances have
been made in developing improved protocols,[10] these approaches
generally require high temperatures and the use of expensive
palladium complexes as promoters. Moreover, in some cases, toxic
CO gas[10a-c] and tin compounds[10b] are used. In addition, these
methods are incompatible with arenes bearing bromide, iodide, OTf
groups, and others. These drawbacks demand that a more cost-
effective, environmentally friendly and mild method for aldehyde
synthesis be devised.
In considering ways to address the challenges associated with
devising a new, truly environmentally friendly strategy for the
synthesis of aldehydes, our attention was drawn to the mild, three-
component amino acid 6 forming Petasis reaction (Scheme 1B).[11]
This process is carried out using aryl boronic acids 1, glyoxylic acid
2 and amines 3 and does not require the use of transition metals for
activation. We believed that this process would serve as the
foundation of an organocatalytic aldehyde forming protocol if the in
[]
[a] H. Huang, Dr. C.-G. Yu, X.-M. Li, Y.-T. Zhang, Prof. Dr. P. S.
Mariano, Prof. Dr. W. Wang
Department of Chemistry & Chemical Biology
University of New Mexico, Albuquerque, NM 87131 (USA)
E-mail: mariano@unm.edu; wwang@unm.edu
[b] X.-M. Li, Dr. Y.-Q. Zhang, Dr. X.-B. Chen, Prof. Dr. W. Wang
State Key Laboratory of Bioengineering Reactor and Shanghai
Key Laboratory of New Drug Design, School of Pharmacy
East China University of Science & Technology
130 Mei-Long Road, Shanghai 200237 (P. R. China)
[] Financial support of this research from the NSF (CHE-1565085)
ACS-PRF (57164-ND1) and the National Science Foundation of
China (21372073 and 21572055) is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201xxxxxx.
1
This article is protected by copyright. All rights reserved.

10.1002/anie.201703127
Angewandte Chemie International Edition
situ formed α-amino acid 6 were properly designed to undergo O2
promoted oxidative decarboxylation to form an iminium ion 7. In
situ hydrolysis of the iminium ion formed in this way would
produce an aldehyde product 4 and liberate the amine as part of a
catalytic cycle. The critical challenge in developing a new
formylation procedure based on this strategy is devising a system
and conditions under which oxidative decarboxylation of amino acid
6 would occur. Knowledge gained from our earlier studies of
oxidative enamine catalysis,[12] aniline catalyzed direct
functionalization of aldehydes[13] and single electron transfer (SET)
promoted formylation[14] and decarboxylation[15] reactions inspired
us to propose that SET induced decarboxylation of amino acids
derived by the Petasis reaction of N-alkylaniline derivatives, such as
tetrahydroquinoline and indoline, might undergo O2 promoted
poorer yield (10 mol%, entry 5). However, we showed that the
protocol can be adapted to a large-scale synthesis of aldehydes with
20 mol% 3a when 3.04 g of 1a was used to produces 2.10 g (77%
yield) of aldehyde 4a (entry 6).
X
X
3a (30 mol%)
CHO
CHO
B(OH)2
+
CHOCO2H H2O
CH3CN, rt, 24-36 h
open to air
1
2
4
[b]
4a
: X = 4-OMe, 75%
CHO
CHO
4b: X = 3-OMe, 70%[b]
4c: X = 2-OMe, 73%[b]
4d: X = 4-SMe, 77%
N
N
NH
N
4e
[c]
: X = 3,4-OCH2O, 64%
4u
: 51%
4w: 81%
4v
: 67%
4f
: X = 4-Ph, 75%
4g: X = 4-Me, 66%[b]
F
Heteraromatic:
CHO
CHO
F
4h: X = 2,4,6-Me3, 63%
F
4i: X = 4-vinyl, 65%
oxidative decarboxylation. This reasoning is based on
a
[c]
4j
: X = 4-Cl, 75%
F
[b]
CHO
F
S
consideration of the respective oxidation potentials of +0.66 and
+0.63 V (vs AgCl/Ag in CH3CN, see SI) for 1-methyl-1,2,3,4-
tetrahydroquinoline and N-methylindoline, and the reduction
potential for O2 (g) which is +0.682 V (AgCl/Ag in water).[16] These
data suggest that SET to O2 from the tetrahydroquinoline and
indoline moieties of the corresponding amino acids would be
4k
: X = H, 66%
4x
: 71%
4y: 51%[b]
4z: 68%
4l: X = 4-OH, 63%
4m: X = 4-NHAc, 55%[c]
[c]
4n
4o
: X = 4-CN, 70%
: X = 4-NO2, 53%
OMe
CHO
[d]
OHC
N
S
S
4p: X = 4-COPh, 75%
4q: X = 4-CHO, 58%
4r: X = 4-CO2H, 55%
CHO
4ac: 75%
O
N
OMe
exergonic and, thus rapid. In contrast, Ered (vs AgCl/Ag) in
4aa: 78%
1/2
4ab: 70%
4s
: X = 4-COOMe, 61%
CH3CN of aliphatic amines such as N-methylpyrrolidine and its
Petasis adduct 2-phenyl-2-(pyrrolidin-1-yl)acetic acid are 0.82 V
and 1.16 V, respectively, which suggest that the latter substance
would not be rapidly oxidized by O2. When coupled to the fact that
aminium radicals formed by SET oxidation of α-amino acids
undergo rapid decarboxylation and that the resulting α-amino
radicals are rapidly oxidatively converted to iminium ions,[15] the
data suggest that O2 will promote oxidative decarboxylation of
secondary aniline derived Petasis adducts 6 to generate iminium
ions 7, which upon hydrolysis will form the target aldehydes 4 and
regenerate the amine organocatalyst 3.
4t: X = 4-SO2Me, 51%
Substrates sensitive to Pd-catalyzed formylation reactions:
Nature product late-stage
modifacation:
O
Br
CHO
CHO
CHO
CHO
H
Br
I
TfO
H
H
Br
4ag: 70%
4ad
4af
: 77%
: 65%
4ae: 50%
4ah: 75%
OHC
Chemoselective formylation of boronic site rather than nucleophilic position 3:
CHO
3
3
OHC
3
N
N
Boc
OHC
N
Boc
4aj
: 63%
4ai: 50%
Boc
4ak
: 65%
Table 1: Exploration and optimization
Scheme 2. Scope of the formylation reaction with aryl boronic acids.
[a] Standard reaction conditions: unless specified, see reaction
conditions in Table 1 and yields refer to isolated ones. [b] NMR yield
with dimethyl maleate as an internal standard. [c] Reaction carried out
at 70 ºC for 24 h. [d] Reaction carried out at 40 ºC for 36 h.
The new methodology described above is applicable to the
synthesis of a variety of aromatic aldehydes (Scheme 2). Notably,
the efficiency of the reaction is not significantly affected by
variations in the aryl boronic acids, as is demonstrated by the
observation that the electronic nature and position of substituents on
the aromatic ring of the substrates do not impact the yields of these
reactions. Notably, the mild nature of the formylation reaction
enables survival of a variety of functional groups. Particularly
noteworthy is the fact that the process is orthogonal to Pd-catalyzed
formylation reactions, which use aryl bromides and iodides as
substrates. In the new process, formylation of aromatic boronic
acids bearing chloride, bromide, iodide and OTf groups occurs
without affecting aryl-halide and -OTf functionalities (eg.,
formation of 4j, and 4ad-4ag). Furthermore, the formylation
protocol is applicable to the production of p-nitrobenzaldehyde (4o)
and pentafluorobenzaldehyde (4y), difficult tasks when transition
metal catalytic methods are employed.[10] In addition, a variety of
structurally diverse aromatic ring containing boronic acids
effectively participate in the process as demonstrated by the
formation of aldehydes 4v-4x in high yields. Moreover,
pharmaceutically relevant heteroaromatic aldehyde building blocks
(eg., 4z-4ac) are efficiently prepared starting with the corresponding
boronic acids. Finally, the new formylation procedure was found to
be applicable to a late-stage synthetic elaboration of a steroidal
boronic acid to generate the biologically relevant aldehyde 4ah.
A major effort has been given to the development of formylation
reactions of indoles, all of which take advantage of the high
nucleophilic reactivity of the C-3 position.[17] Devising methods for
formylation at other positions of this heterocycle ring system are
plagued by difficulties associated with regiocontrol and poor
entry deviation from "standard conditions"[a] % yield[b]
1
2
3
4
5
6
-
75 (75)c
under N2 (without O2)
without 3a
0
0
Pyrrolidine[d]
0
10 mol% 3a used
20 mol% 3a and 3.04 g of 1a used
23
77[c]
[a] Standard reaction conditions: unless specified, a mixture of 1a (0.2
mmol, 1.0 equiv), 2 (0.21 mmol, 1.05 equiv.) and 3a (30 mol %) in
CH3CN (5.0 mL) was stirred at rt under ambient conditions for 24-36 h
and see SI for detail. [b] Yields were determined by using 1H NMR
with dimethyl maleate as an internal standard. [c] Isolated yields. [d]
Petasis product observed.
Proof-of-concept of the newly proposed formylation strategy
began with a study of the reaction of 4-methoxyphenylboronic acid
(1a) with glyoxylic acid monohydrate (2) in the presence of
tetrahydroquinoline 3a in CH3CN under ambient conditions and an
air atmosphere (Table 1). In full accord with our proposal, the
process proceeds efficiently to form the desired aldehyde 4a in 75%
yield. (entry 1). In the absence of an air atmosphere, 4a is not
generated (entry 2) but instead the Petasis product is formed. In
addition to O2, 3a is essential for the process (entry 3). Furthermore,
only the Petasis reaction derived amino acid is formed when
pyrrolidine is used as the promoter and conditions are employed that
are identical to those used for 3a catalyzed conversion of boronic
acid 1a to aldehyde 4a (entry 4). Lower catalyst loading delivered
2
This article is protected by copyright. All rights reserved.

10.1002/anie.201703127
Angewandte Chemie International Edition
functional group compatibility. Given the fact that other
regioisomeric formyl-indoles are highly valuable building blocks for
the synthesis of a broad range of indole ring containing substances,
we explored formylation reactions of several N-Boc protected indole
boronic acid. As can be seen by viewing the results outlined in
Scheme 2, N-Boc protected 6-, 5- and 4-boronic acid derivatives of
indole are efficiently converted to the corresponding formylindoles
4ai-4ak utilizing the newly developed protocol.
It is should be noted that reaction of 4-cyanophenylboronic acid
under the optimized conditions produced the target aldehyde 4n
along with a significant amount (33%) of 4-cyanophenol. This
observation indicates that a reactive oxygen species (eg., hydrogen
peroxide, superoxide ion), formed under the oxygen rich conditions
oxidizes 4-cyanophenylboronic acid to form the corresponding
phenol.[3b] We observed that side-product phenols of this type in
reactions that form 4j, 4m-4n and 4v can be reduced by carrying out
the processes at 70 ºC (Scheme 2).
(Scheme 4, Eq. 1). Aliphatic amine like pyrrolidine participate in the
formation of the Petasis product, but the derived amino acids do not
undergo subsequent oxidative decarboxylation in air (Table 1, entry
4). Thus, the selection of a proper amine catalysts is critical
requirement for the success of the new formylation protocol. As
discussed above, the N-alkylaniline derivatives have lower redox
potentials than that of O2 and, therefore, they undergo rapid SET
oxidation in air (O2). In contrast, aliphatic amines can be oxidized
by O2 but only with the assistance of light in the presence of
photosensitizer.[15,17,21] In a similar manner to the photochemical
processes,[15,22] the O2 mediated SET process initially generates an
aminium radical 10k and superoxide ion (Scheme 4). The aminium
radical 10k then undergoes decarboxylation to form -amino radical
11k, which is oxidized to produce the iminium ion 7k with
concurrent production of H2O2.[15] We observed phenol side
products in the formylation reaction, particularly 4j, 4m-4n and 4v.
It is believed that their formation comes from the oxidation of
boronic acids by H2O2 (see above).[3b]
Scheme 3. Formylation reactions of alkenyl boronic acids. [a]
Standard reaction conditions: unless specified, see Scheme 2 and SI
for details. [b] Isolated yields. [c] cis-Styrylboronic acid used.
To determine if the scope of the new procedure could be
expanded to include the preparation of enals 9 (Scheme 3), which
are versatile substances used in iminium catalysis,[18] we explored
formylation reactions of several alkenylboronic acids 8. Using the
optimized conditions developed for formylation of aryl boronic
acids (see above), which utilize tetrahydroquinoline 3a as the
organocatalyst, β-styryl boronic acid is transformed to
cinnamaldehyde (9a) but in only 10% yield (see Scheme S2 in SI).
A brief screen of amines demonstrated that indoline (3b) is a
superior catalyst for preparation of 9a from the corresponding
boronic acid, which takes place in 70% yield. Moreover, we
observed that formylation reactions employing 3b as the
organocatalyst occur efficiently to produce the corresponding enals
9 (Scheme 3) with moderate to high efficiency. However, we found
that cis styrylboronic acid 8a also generated trans enal 9a under the
formylation reaction conditions. It is known that 8a produced a
Petasis product that contains a cis styryl moiety.[19] This observation
suggests that the initially formed cis radical intermediate in the SET-
promoted decarboxylation process equilibrates to form the
thermodynamically more stable trans counterpart prior to oxidation
to form the iminium ion (see Scheme 4 and Scheme S3).[20]
Scheme 4. Experiments to elucidate subtle features and proposed
catalytic cycle involving oxidative SET decarboxylation for the
formylation reaction.
In conclusion, in the study described above we uncovered an
unprecedented organocatalytic method for facile installation of the
highly valued aldehyde functional group from aryl and alkenyl
boronic acids. The reaction is truly environmentally friendly and
atom
economical.
The
simple
aniline
derivatives,
The results presented above suggest that the initially formed
amino acid 6, produced by the Petasis reaction between boronic
acids, glyoxylic acid 2, and aromatic amines like 3a, undergo the
oxidative decarboxylation to produce the iminium ion precursor of
aldehyde 7 (Schemes 1B and 4). Several experiments were carried
out to gain information about subtle features of the process and the
validity of our mechanistic proposals. First, the in situ formed
Petasis product 6k and iminium ion 7k intermediate in the 3a
promoted reaction of phenylboronic acid with 2 were detected by
using in situ mass spectrometric analysis (SI). Moreover, we found
that the 3a promoted reaction of glyoxylic acid with phenylboronic
acid, carried out under O2 free conditions, does not generate the
corresponding aldehyde 4k (Table 1, entry 2). Furthermore, amino
acid 6k, the proposed Petasis intermediate in this formylation
process, was independently synthesized (see SI) and found to be
quantitatively transformed under an air atmosphere (CDCl3, rt,
overnight, 1H NMR analysis) to benzaldehyde 4k and amine 3a
tetrahydroquinoline and indoline, serve as catalysts for the process
and the feedstock chemical glyoxylic acid is used as the formylation
reagent. The reaction is performed under metal-free, mild and
operationally simple conditions and produces non-toxic CO2 and
boric acid as by-products. The new formylation reaction displays a
broad substrate range that includes aryl, heteroaryl and alkenyl
boronic acids, and it tolerates a wide array of functional groups.
Notably, the process is capable of selectively installing the aldehyde
group in halogen-contained aryl boronic acids, which stands in
contrast with the difficulty of executing these transformations using
transition metal promoted formylation processes. Furthermore,
selective formylation of N-Boc indole derived boronic acids can be
utilized to generate indole aldehydes that have the formyl group at
positions other than C3. It is expected that the simplicity and
efficiency of the new formylation reaction will make it useful in
approaches for the practical production of highly valued aromatic
and α, β-unsaturated aldehydes.
3
This article is protected by copyright. All rights reserved.

10.1002/anie.201703127
Angewandte Chemie International Edition
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
[10] a) I. Pri-Bar, O. Buchman, J. Org. Chem. 1984, 49, 4009; b) V. P.
Baillargeon, J. K. Stille, J. Am. Chem. Soc. 1986, 108, 452; c) S.
Klaus, H. Neumann, A. Zapf, D. Strubing, S. Hubner, J. Almena, T.
Riemeier, P. Gross, M. Sarich, W. R. Krahnert, K. Rossen, M. Beller,
Angew. Chem. Int. Ed. 2006, 45, 154; Angew. Chem. 2006, 118, 161;
d) S. Korsager, R. H. Taaning, T. Skrydstrup, J. Am. Chem. Soc. 2013,
135, 2891. e) K. Natte, A. Dumrath, H. Neumann, M. Beller, Angew.
Chem. 2014, 126, 10254; Angew. Chem. Int. Ed. 2014, 53, 10090; f)
W. Wu, W.-P. Su, J. Am. Chem. Soc. 2011, 133, 11924; g) B. Yu, Y. F.
Zhao, H. Y. Zhang, J. L. Xu, L. D. Hao, X. Gao, Z. M. Liu, Chem.
Commun. 2014, 50, 2330.
[11] a) N. A. Petasis, I. Akritopoulou, Tetrahedron Lett. 1993, 34, 583; b)
N. A. Petasis, I. A. Zavialov, J. Am. Chem. Soc. 1997, 119, 445; c) J.
Zhu, H. Bienayme, Multicomponent Reactions. Wiley-VCH,
Weinheim 2005.
[12] S.-L. Zhang, H.-X. Xie, J. Zhu, H. Li, X.-S. Zhang, J. Li, W. Wang,
Nat. Commun. 2011, 2, 211.
Keywords: boronic acids feedstock chemicals
formylation · organocatalysis synthetic methods
[1] a) D. G. Hall, Boronic Acids: Preparation and Applications in
Organic Synthesis, Medicine and Materials. Second edition. Wiley-
VCH, Weinheim 2011, Vol. 1. b) T. Kalliokoski, ACS Comb. Sci.
2015, 17, 600.
[2] For selected reviews of borylation reactions, see: a) I. A. I. Mkhalid, J.
H. Barnard, T. B. Marder, J. M. Murphy, J. F. Hartwig, Chem. Rev.
2010, 110, 890. b) J. F. Hartwig, Acc. Chem. Res. 2012, 45, 864. c) A.
Ros, R. Fernandez, J. M. Lassaletta, Chem. Soc. Rev. 2014, 43, 3229.
d) E. C. Neeve, S. J. Geier, I. A. Mkhalid, S. A. Westcott, T. B.
Marder, Chem. Rev. 2016, 116, 9091. e) W. K. Chow, O. Y. Yuen, P.
Y. Choy, C. M. So, C. P. Lau, W. T. Wong, F. Y. Kwong, RSC Adv.
2013, 3, 12518. f) R. D. Dewhurst, E. C. Neeve, H. Braunschweig, T.
B. Marder, Chem. Commun. 2015, 51, 9594. g) A. B. Cuenca, R.
Shishido, H. Ito, E. Fernandez, Chem. Soc. Rev. 2017, 46, 415.
[3] a) R. E. Maleczka Jr, F. Shi, D. Holmes, M. R. Smith III, J. Am. Chem.
Soc. 2003, 125, 7792. b) Y. Q. Zou, J. R. Chen, X. P. Liu, L. Q. Lu, R.
L. Davis, K. A. Jørgensen, W.-J. Xiao, Angew. Chem. 2012, 124, 808;
Angew. Chem. Int. Ed. 2012, 51, 784.
[4] a) G. K. Prakash, C. Panja, T. Mathew, V. Surampudi, N. A. Petasis,
G. A. Olah, Org. Lett. 2004, 6, 2205. b) H. Rao, H. Fu, Y. Jiang, Y.
Zhao, Angew. Chem. 2009, 121, 1134; Angew. Chem. Int. Ed. 2009,
48, 1114.
[5] a) R. H. Szumigala Jr, P. N. D. R. Devine, Gauthier Jr, R. P. Volante,
J. Org. Chem. 2004, 69, 566. b) H. Wu, J. Hynes Jr. Org. Lett. 2010,
12, 1192. c) T. Furuya, H. M. Kaiser, T. Ritter, Angew. Chem. 2008,
120, 6082; Angew. Chem. Int. Ed. 2008, 47, 5993.
[13] C.-G. Yu, H. Huang, X.-M. Li, Y.-T. Zhang, H. Li, W. Wang, Chem.
Eur. J. 2016, 22, 9240.
[14] Recently we reported
a photoredox and nickel co-catalyzed
formylation of aryl halides: H. Huang, X.-M. Li, C.-G. Yu, Y.-T.
Zhang, P. S. Mariano, W. Wang, Angew. Chem. 2017, 129, 1522;
Angew. Chem. Int. Ed. 2017, 56, 1500.
[15] a) Z. Su, D. E. Falvey, U. C. Yoon, P. S. Mariano, J. Am. Chem. Soc.
1997, 119, 5261; b) Z. Su, P. S. Mariano, D. E. Falvey, U. C. Yoon, S.
W. Oh, J. Am. Chem. Soc. 1998, 120, 10676; c) X. M. Zhang, Y. S.
Jung, P. S. Mariano, M. A. Fox, P. S. Martin, J. Merkert, Tetrahedron
Lett. 1993, 34, 5239.
[16] E. Yeager, Electrochim. Acta 1984, 29, 1527.
[17] a) X. Li, X. Gu, Y. Li, P. Li, ACS Catal. 2014, 4, 1897; b) L-T. Li, J.
Huang, H-Y. Li, L.-J. Wen, P. Wang, B. Wang, Chem. Commun. 2012,
48, 5187. c) J. Chen, B. Liu, D. Liu, S. Liu, J. Cheng, Adv. Synth.
Catal. 2012, 354, 2438. d) H. Fei, J. Yu, Y. Jiang, H. Guo, J. Cheng,
Org. Biomol. Chem. 2013, 11, 7092.
[18] A. Erkkilä, I. Majander, P. M. Pihko, Chem. Rev. 2007, 107, 5416.
[19] B. Jiang, M. Xu, Org. Lett. 2002, 4, 4077.
[20] a) R. M. Hoyte, D. B. Denney, J. Org. Chem. 1974, 39, 2607. b) D. B.
Denney, R. M. Hoyte, P. T. Macgrego, Chem. Commun. 1967, 1241.
[21] A. G. Condie, J. C. Gonzalez-Gomez, C. R. J. Stephenson, J. Am.
Chem. Soc. 2010, 132, 1464.
[6] A. D. Meijere, F. O. Diederich, Metal-catalyzed cross-coupling
reactions. 2nd, Wiley-VCH: Weinheim, 2004.
[7] L. N. Ferguson, Chem. Rev. 1946, 38, 227.
[8] a) Reimer-Tiemann reaction: Wynberg, H. Chem. Rev. 1960, 60, 169;
b) Vielsmeier–Haack reaction: G. Jones, S. P. Stanforth, Org. React.
2004, 56, 355; c) Gattermann–Koch reaction: N. N. Crounse, Org.
React. 2011, 5, 290; d) Duff reaction: J. C. Duff, E. J. Bills, J. Chem.
Soc. 1932, 1987.
[22] C. Huo, Y. Yuan, M. Wu, X. Jia, X. Wang, F. Chen, J. Tang, Angew.
Chem. 2014, 126, 13762; Angew. Chem. Int. Ed. 2014, 53, 13544.
[9] A. Schoenberg, I. Bartolet, R. F. Heck, J. Org. Chem. 1974, 39, 3318.
4
This article is protected by copyright. All rights reserved.

10.1002/anie.201703127
Angewandte Chemie International Edition
Entry for the Table of Contents (Please choose one layout)
Organocatalysis
He Huang, Chenguang Yu,
Xiangmin Li, Yongqian Zhang,
Yueteng Zhang, Xiaobei Chen,
Patrick S. Mariano,* Hexin Xie*
and Wei Wang*______ Page –
Page
Synthesis of Aldehydes by
Organocatalytic Formylation
Reactions of Boronic Acids with
A conceptually novel organocatalytic strategy for synthesis of aldehydes is reported. A new
reactivity is engineered into the α-amino acid forming Petasis reaction to create an
unprecedented amine promoted formylation of boronic acids using glyoxylic acid as a
formylation reagent.
Glyoxylic Acid
5
This article is protected by copyright. All rights reserved.