Synthesis of Ketones by C?H Functionalization of Aldehydes with Boronic Acids under Transition-Metal-Free Conditions

Article abstract of DOI:10.1002/anie.202015835

A method for the synthesis of ketones from aldehydes and boronic acids via a transition-metal-free C?H functionalization reaction is reported. The method employs nitrosobenzene as a reagent to drive the simultaneous activation of the boronic acid as a boronate and the activation of the C?H bond of the aldehyde as an iminium species that triggers the key C?C bond-forming step via an intramolecular migration from boron to carbon. These findings constitute a practical, scalable, and operationally straightforward method for the synthesis of ketones.

Full text of DOI:10.1002/anie.202015835

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How to cite: Angew. Chem. Int. Ed. 2021, 60, 8728–8732
International Edition:
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doi.org/10.1002/anie.202015835
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Synthetic Methods
À
Synthesis of Ketones by C H Functionalization of Aldehydes with
Boronic Acids under Transition-Metal-Free Conditions
Silvia Roscales and Aurelio G. Csꢀky*
Abstract: A method for the synthesis of ketones from
aldehydes and boronic acids via a transition-metal-free CÀH
We became interested in exploiting the reaction between
[
13]
aldehydes and nitrosobenzene (Scheme 1c) in connection
with previous research concerning new reactions that involve
functionalization reaction is reported. The method employs
nitrosobenzene as a reagent to drive the simultaneous activa-
tion of the boronic acid as a boronate and the activation of the
CÀH bond of the aldehyde as an iminium species that triggers
the key CÀC bond-forming step via an intramolecular migra-
[
14]
boronic acids and nitroso compounds. Boronic acids are
well known for their ability to act as bench-stable carbon
[15]
[16]
nucleophiles.
Due to their low reactivity,
they have
mostly been used in combination with transition-metals. CÀC
tion from boron to carbon. These findings constitute a practical,
scalable, and operationally straightforward method for the
synthesis of ketones.
bond formation using boronic acids as reagents under
[
17]
transition-metal-free conditions is comparatively rare.
[
1]
K
etones are important structural motifs and building
[
2]
blocks in organic chemistry (Scheme 1a). Despite the
many reactions available for their synthesis (e.g. reaction of
carboxylic acid derivatives with organometallic reagents,
transition-metal-catalyzed cross-couplings, Friedel–Crafts or
[3,4]
Mannich reactions),
there is a continuous need for the
development of new ways to improve their preparation in
search of rapid methods that use readily available starting
materials. This is the case of the CÀH functionalization of
aldehydes (Scheme 1b), that is, the replacement of their
2
2
[5]
C(sp )ÀH bond for a C(sp )ÀC bond. For this reaction to be
highly efficient, it is imperative to find friendly-to-use
reagents and avoid the use of toxic metals, cumbersome
additives, or harsh reaction conditions.
Aldehydes have been used profusely as starting materials
for the synthesis of ketones. Aside from the classic two-step
procedure that consists of the addition of a carbon nucleo-
phile, for example, a Grignard reagent, followed by the
[6]
oxidation of the intermediate secondary alcohol, aldehydes
have been converted to ketones by making use of umpolung
[
7,8]
reactions that render acyl anion equivalents.
More
[
9]
[10]
recently, the use of acyl radicals, carbonyl Heck reactions
and other related transition-metal-catalyzed additions as
[
11]
[
12]
well as hydroacylation reactions have been gaining popu-
larity for the direct synthesis of ketones from aldehydes.
However, most of these methods rely on the use of strong
bases, transition-metals, ancillary ligands, or harsh reaction
conditions. Also, many of them are restricted to a particular
type of aldehyde, either aliphatic or aromatic.
[
*] Dr. S. Roscales, Prof. Dr. A. G. Csꢀky
Instituto Pluridisciplinar, Universidad Complutense, Campus de
Excelencia Internacional Moncloa
Paseo de Juan XXIII, 1, 28040 Madrid (Spain)
E-mail: csaky@ucm.es
Scheme 1. A) Synthetic utility of ketones. B) Synthesis of ketones from
aldehydes. C) Reaction intermediates in the formation of hydroxamic
acids from aldehydes and nitrosobenzene. D) Typical mechanism of
the Petasis-Mannich reaction. E) C(sp )-H aldehyde activation with
boronic acids and nitrosobenzene leading to ketones.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202015835.
2
8728
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However, the interaction of the vacant orbital on the boron
atom of boronic acids with a nucleophile renders boronates
“ate” complexes), which show enhanced nucleophilicities.
obtainment of the corresponding ketones 5 and 6 in good
yields and short reaction times (2 h, TLC following).
(
With these observations in hand, we extended the reaction
to a variety of aldehydes and boronic acids (Scheme 3).
Keeping 2a as the reaction partner, we observed that the
reaction was very general for the aldehyde counterpart
(Scheme 3a), tolerating other a-hetero functionalized alde-
hydes (7–9) that included the acid-labile TBSO group (7) and
a proline derivative (9) that reacted without epimerization
The ability of boronates to engage in migration reactions
triggered by the presence of a nearby electrophilic site is one
[
18]
of the most relevant reactions in boron chemistry.
In
particular, the activation of boronic acids with oxygen
nucleophiles permits the transformation of a-hydroxyalde-
[
19]
hydes into amines (the Petasis-Mannich reaction). In this
reaction, coordination of a vinyl or aryl boronic acid to the
hydroxy moiety generates a boronate intermediate that
intermolecularly transfers its carbon group to the electro-
philic iminium species formed by the interaction of the
aldehyde with a primary or secondary amine (Scheme 1d).
Recently disclosed reactions of other compounds that bear an
oxygen site for coordination of the boronic acid and a nearby
[
24]
(see SI),
1,2-dicarbonyl derivatives (10, 11), a,b-unsatu-
rated aldehydes (12, 13), aliphatic aldehydes (14–16) and
aromatic aldehydes (6, 17–21) including examples with
electron-donor substituents (17, 18), ortho-substitution (18),
and electron-accepting substituents (19–21). a-Hetero func-
tionalized (4, 7, 8) aldehydes reacted with 2a at rt allowing the
synthesis of the corresponding ketones in good yields. More
hindered (5, 9, 16) and a,b-unsaturated aldehydes (12, 13)
also reacted at rt but in moderate yields, which were increased
upon heating. However, aromatic aldehydes (6, 17–21) and
1,2-dicarbonyl derivatives (10, 11) required the reaction to be
performed at 1108C. To demonstrate the potential synthetic
utility of this methodology, two of the examples (4 and 6)
were executed on a 1 g scale with similar yields (see the
Supporting Information for details).
[
20]
iminium-type functionality, such as heterocyclic N-oxides
[
21]
[22]
or nitrile oxides, follow related pathways. We envisioned
that the intermediates formed by the interaction of aldehydes
[
13]
with nitrosobenzene could play a similar role. We report
here (Scheme 1e) that the interaction of aldehydes with
nitrosobenzene in the presence of boronic acids can lead to
intermediates with boronate character that enable the
activation of the aldehyde CÀH bond via iminium-ion
formation, giving rise to the transformation of aldehydes
into ketones by a key 1,4-migration from boron to carbon in
a one-pot procedure that takes place under mild conditions.
We started by selecting 2-benzyloxyacetaldehyde (1a) as
the model aldehyde (Scheme 2a). This is a highly reactive
aldehyde prone to self-condensation by aldol reactions under
acidic or basic conditions. The CÀH activation reactions of 1a
Next, using benzyloxyacetaldehyde (1a), cyclopropane-
carbaldehyde (1b), benzaldehyde (1c), ethyl glyoxylate (1d),
and cinnamaldehyde (1e) as representative examples of
different types of aldehydes, we explored additional synthetic
examples illustrating the reaction scope with regard to the
boronic acid component 2 (Scheme 3b). The reaction was
general with alkenylboronic acids, and ketones 22–27, 43 and
45 were obtained in high yields both at rt (conditions A) and
heating at 1108C (conditions B). Concerning steric hindrance,
we observed that substitution at the a-carbon was tolerated
(28, 29, 46, 48, 50). The reaction also took place with
phenylboronic acid (30) in moderate yield, but high con-
versions were obtained with arylboronic acids bearing
electron-donor substituents (31, 32). However, the presence
of an electron-acceptor substituent on the benzene ring was
not permitted (33). We were pleased to find that the reaction
was also useful for the synthesis of ketones using heterocyclic
boronic acids such as furan (35), thiophene (34, 36), benzo-
furan (37, 39, 44, 47, 49) benzothiophene (38, 40), and indole
(41) derivatives, both with the boronic acid substituent at
positions 2 (34, 37, 38, 44, 47, 49) or 3 (35, 36, 39–41) of the
heterocyclic ring. Unfortunately, the reaction did not take
place with alkylboronic acids like benzylboronic acid (42).
We performed several additional experiments to gain
insight into a plausible reaction course (see the Supporting
Information for details). As expected, no reaction was
observed upon mixing the aldehyde 1a with the boronic
acid 2a in the absence of nitrosobenzene (3a) (Scheme 4a).
No reaction was found between the aldehyde 1a and nitro-
sobenzene (3a) in the absence of the boronic acid (2a) and
the evolution of 3a into azoxybenzene 51 was the only
reaction observed upon mixing 3a with 2a in the absence of
the aldehyde, which is consistent with the Lewis acid
give rise to a-acyloxyketones, which are frequent motifs in
[23]
biologically active natural products and pharmaceuticals.
Initial discovery and optimization experiments were carried
out with 2-phenylvinylboronic acid (2a) using commercial-
grade solvents without exclusion of air or humidity. A survey
of the reaction conditions was performed (see the Supporting
Information for details). Eventually, the optimized reaction
conditions for the synthesis of ketone 4 emerged as 1.5 equiv-
alents of alkenylboronic acid and 1.1 equivalents of nitro-
sobenzene in toluene at rt. However, when 1a was replaced
with the more encumbered cyclopropanecarbaldehyde (1b)
or with benzaldehyde (1c) (Scheme 2b) yields at rt were
significantly lower. We were pleased to find that in these cases
an increase in temperature (toluene, 1108C) allowed the
[
25]
character of boronic acids. We also checked that alcohol
Scheme 2. Optimized reaction conditions.
52 was not oxidized by nitrosobenzene, discarding a reaction
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Scheme 3. Scope and limitations. Conditions A: rt, 18 h. Conditions B: 1108C, 2 h. A) Variation of the aldehyde coupling partner. B) Variation of
the boronic acid coupling partner. With the exception of compounds 4 and 6, which were prepared on 1 g scale, yields are reported for isolated
material following purification on a 0.20 mmol scale. See Supporting Information for full experimental details and conditions.
pathway with 52 as an intermediate in the synthesis of the
corresponding ketone (Scheme 4b). The reaction was not
inhibited in the presence of 1,4-benzoquinone or styrene
which excluded a radical pathway that might have been
induced by the redox properties of nitrosobenzene, and no
variation in yield was observed when the reaction was
executed in degassed anhydrous toluene or under oxygen
atmosphere, which ruled out the participation of oxygen in
the reaction course. These experiments did not permit the
1
trapping of any reaction intermediate. In situ H NMR
spectroscopy in [D ]benzene at rt revealed a slow conversion
6
of the reactants benzyloxyacetaldehyde (1a), phenylvinylbor-
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tion to IV. The collapse of this aminal-type intermediate upon
hydrolysis renders the final ketone.
In conclusion, we have demonstrated that aldehydes can
be directly converted into ketones in a one-pot reaction with
boronic acids in the presence of nitrosobenzene. The process
takes place under mild conditions, does not require transition-
metals, and is general for a wide variety of aldehydes, and for
alkenyl and arylboronic acids, constituting a practical, scal-
able, and operationally easy method for the synthesis of
ketones that can be particularly attractive from the standpoint
of late-stage functionalization.
Acknowledgements
Scheme 4. Additional experiments. A) Reactions in the absence of one
component. B) Attempted reaction of alcohol 52.
Project RTI2018-096520-B-I00 from the Spanish government
(MICINN) is acknowledged for financial support.
onic acid (2a) and nitrosobenzene (3a) into ketone 4, without
evidence of any detectable intermediate. Control experiments
using either the pinacol ester or potassium trifluoroborate Conflict of interest
analog of boronic acid 2a failed to yield the expected ketone.
This provides evidence towards the formation of an anionic
nucleophilic boron species during the reaction mechanism,
since pinacol boronic esters are reluctant to the formation of
boronate species. Also, the migration of the carbon back-
bone of the boronate in the key intermediate must be
intramolecular since the highly nucleophilic trifluoroborate
The authors declare no conflict of interest.
Keywords: aldehydes · boron · CÀC coupling · ketones ·
[
26]
synthetic methods
analog of 2a did not react. Attempts to form a more
2
[1] a) M. C. Cuquerella, V. Lhiaubet-Vallet, J. Cadet, M. A. Mir-
anda, Acc. Chem. Res. 2012, 45, 1558 – 1570; b) Y. Tan, K. J.
Siebert, J. Agric. Food Chem. 2004, 52, 3057 – 3064; c) R.
McDaniel, A. Thamchaipenet, C. Gustafsson, H. Fu, M. Betlach,
M. Betlach, G. Ashley, Proc. Natl. Acad. Sci. USA 1999, 96,
1846 – 1851; d) P. V. Kamat, Chem. Rev. 1993, 93, 267 – 300.
electrophilic species (R BF ) by treatment of the potassium
2
trifluoroborate analog of 2a with TMSCl or BF led to
3
[27]
multiple unidentifiable reaction products. Additional spec-
troscopic and computational studies are underway in order to
further delineate the mechanism of the reaction.
[
2] a) Modern Carbonyl Chemistry (Ed.: J. Otera), Wiley-VCH,
Weinheim, 2000; b) N. J. Lawrence, J. Chem. Soc. Perkin Trans.
In light of these pieces of evidence and the above cited
previous literature precedents concerning the reactions of
1
1998, 1739 – 1749; c) M. Blangetti, H. Rosso, C. Prandi, A.
[
13]
aldehydes with nitrosobenzene
reaction,
and the Petasis-Mannich
Deagostino, P. Venturello, Molecules 2013, 18, 1188 – 1213.
3] See reference [2], and in addition: a) S. Nahm, S. M. Weinreb,
Tetrahedron Lett. 1981, 22, 3815 – 3818; b) G. Sartori, R. Maggi,
Chem. Rev. 2006, 106, 1077 – 1104; c) W. S. Bechara, G. Pelletier,
A. B. Charette, Nat. Chem. 2012, 4, 228 – 234; d) N. Miyaura, A.
Suzuki, Chem. Rev. 1995, 95, 2457 – 2483; e) M. C. Willis, Chem.
Rev. 2010, 110, 725 – 748; f) X.-F. Wu, H. Neumann, M. Beller,
Chem. Soc. Rev. 2011, 40, 4986 – 5009; g) T. Moragas, A. Correa,
R. Martin, Chem. Eur. J. 2014, 20, 8242 – 8258; h) R. K. Dieter,
Tetrahedron 1999, 55, 4177 – 4236; i) M. Iinuma, K. Moriyama,
H. Togo, Tetrahedron 2013, 69, 2961 – 2970; j) Y. Huang, R. Zhu,
K. Zhao, Z. Gu, Angew. Chem. Int. Ed. 2015, 54, 12669 – 12672;
Angew. Chem. 2015, 127, 12860 – 12863; k) M. Giannerini, C.
Vila, V. Hornillos, B. L. Feringa, Chem. Commun. 2016, 52,
[
19,28]
we concluded that coordination of the oxygen of
[
the aldehyde with the boronic acid can trigger the nucleo-
philic addition of nitrosobenzene (Scheme 5), generating
a low equilibrium concentration of the labile intermediate I,
which has boronate character and an enhanced acidity of the
original aldehyde hydrogen atom. Cyclization to III generates
an iminium-type electrophile in the proximity of the nucle-
ophilic boronate center, which rapidly evolves by 1,4-migra-
1206 – 1209; l) A. T. Wolters, V. Hornillos, D. Heijnen, M.
Giannerini, B. L. Feringa, ACS Catal. 2016, 6, 2622 – 2625;
m) L.-J. Cheng, N. P. Mankad, J. Am. Chem. Soc. 2017, 139,
10200 – 10203.
[
4] For some additional recent methods, see: a) J. Wang, B. P. Cary,
P. D. Beyer, S. H. Gellman, D. J. Weix, Angew. Chem. Int. Ed.
2
019, 58, 12081 – 12085; Angew. Chem. 2019, 131, 12209 – 12213;
b) F. Q. Zhao, C. L. Li, X. F. Wu, Chem. Commun. 2020, 56,
182 – 9185; c) J. Wang, M. E. Hoerrner, M. P. Watson, D. J.
9
Weix, Angew. Chem. Int. Ed. 2020, 59, 13484 – 13489; Angew.
Chem. 2020, 132, 13586 – 13591; d) R. Ruzi, K. Liu, C. Zhu, J.
Xie, Nat. Commun. 2020, 11, 3312; e) N. Chalotra, S. Sultan,
B. A. Shah, Asian J. Org. Chem. 2020, 9, 863 – 881; f) H. Cao, Y.
Scheme 5. Proposed reaction course.
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Kuang, X. Shi, K. L. Wong, B. B. Tan, J. M. C. Kwan, X. Liu, J.
Wu, Nat. Commun. 2020, 11, 1956, and references therein.
5] P. Kumar, S. Dutta, S. Kumar, V. Bahadur, E. V. Van der Eycken,
K. S. Vimaleswaran, V. S. Parmar, B. K. Singh, Org. Biomol.
Chem. 2020, 18, 7987 – 8033.
Amsterdam, 2014, pp. 961 – 994; d) M. A. Garralda, Dalton
Trans. 2009, 3635 – 3645.
[
[13] a) O. Kronja, J. Matijevi c´ -Sosa, S. Ur sˇ i c´ , J. Chem. Soc. Chem.
Commun. 1987, 463 – 464; b) M. Strah, S. Ur sˇ i c´ , B. Zorc, Croat.
Chem. Acta 1989, 62, 529 – 535; c) S. Ur sˇ i c´ , Helv. Chim. Acta
1993, 76, 131 – 138; d) S. Ur sˇ i c´ , V. Pilepic, V. Vrcek, M.
Gabricevic, B. Zorc, J. Chem. Soc. Perkin Trans. 2 1993, 509 –
514.
[
6] J. E. Steves, S. S. Stahl, J. Am. Chem. Soc. 2013, 135, 15742 –
15745.
[
7] For the Corey-Seebach reaction, see: a) E. J. Corey, D. Seebach,
Angew. Chem. Int. Ed. Engl. 1965, 4, 1077 – 1078; Angew. Chem.
[14] a) S. Roscales, A. G. Csaky, Org. Lett. 2018, 20, 1667 – 1671; b) S.
Roscales, A. G. Csꢁkꢂ, J. Chem. Educ. 2019, 96, 1738 – 1744; c) S.
Roscales, A. G. Csaky, ACS Omega 2019, 4, 13943 – 13953.
[15] Boronic Acids: Preparation and Applications in Organic Syn-
thesis Medicine and Materials (Ed.: D. G. Hall), Wiley-VCH,
Weinheim, 2011.
1
965, 77, 1136 – 1137; b) A. B. Smith, C. M. Adams, Acc. Chem.
Res. 2004, 37, 365 – 377; c) B. Yucel, Adv. Synth. Catal. 2014, 356,
659 – 3667; d) S. A. Baker Dockrey, A. K. Makepeace, J. R.
3
Schmink, Org. Lett. 2014, 16, 4730 – 4733; e) K. Yao, D. Liu, Q.
Yuan, T. Imamoto, Y. Liu, W. Zhang, Org. Lett. 2016, 18, 6296 –
6
299; f) N. Trongsiriwat, M. Li, A. Pascual-Escudero, B. Yucel,
[16] G. Berionni, B. Maji, P. Knochel, H. Mayr, Chem. Sci. 2012, 3,
878 – 882.
P. J. Walsh, Adv. Synth. Catal. 2019, 361, 502 – 509.
[
8] For N-heterocyclic carbene-catalyzed reactions, see: a) D. A.
DiRocco, T. Rovis, Asymmetric Benzoin and Stetter Reactions
Vol. 2, Georg Thieme, Stuttgart, 2011, pp. 835 – 862; b) A. A.
Rajkiewicz, M. Kalek, Org. Lett. 2018, 20, 1906 – 1909; c) A. A.
Rajkiewicz, N. Wojciechowska, M. Kalek, ACS Catal. 2020, 10,
[17] a) S. Roscales, A. G. Csaky, Chem. Soc. Rev. 2014, 43, 8215 –
8225; b) F. Sanchez-Sancho, A. G. Csaky, Synthesis 2016, 48,
2165 – 2177.
[18] a) H. Wang, C. Jing, A. Noble, V. K. Aggarwal, Angew. Chem.
Int. Ed. 2020, 59, 16859 – 16872; Angew. Chem. 2020, 132, 17005 –
17018; b) M. Kischkewitz, F. W. Friese, A. Studer, Adv. Synth.
Catal. 2020, 362, 2077 – 2087; c) K. K. Das, S. Panda, Chem. Eur.
J. 2020, 26, 14270 – 14282; d) S. Paul, K. K. Das, S. Manna, S.
Panda, Chem. Eur. J. 2020, 26, 1922 – 1927; e) S. Namirembe, J. P.
Morken, Chem. Soc. Rev. 2019, 48, 3464 – 3474; f) S. Roscales,
A. G. Csꢁky, Chem. Soc. Rev. 2020, 49, 5159 – 5177.
[19] a) N. A. Petasis, I. Akritopoulou, Tetrahedron Lett. 1993, 34,
583 – 586; b) N. R. Candeias, F. Montalbano, P. M. S. D. Cal,
P. M. P. Gois, Chem. Rev. 2010, 110, 6169 – 6193; c) P. Wu, M.
Givskov, T. E. Nielsen, Chem. Rev. 2019, 119, 11245 – 11290.
[20] L. Bering, A. P. Antonchick, Org. Lett. 2015, 17, 3134 – 3137.
[21] K. Yang, F. Zhang, T. C. Fang, G. Zhang, Q. L. Song, Angew.
Chem. Int. Ed. 2019, 58, 13421 – 13426; Angew. Chem. 2019, 131,
13555 – 13560.
831 – 841.
[
9] a) L. Wang, T. Wang, G.-J. Cheng, X. Li, J.-J. Wei, B. Guo, C.
Zheng, G. Chen, C. Ran, C. Zheng, ACS Catal. 2020, 10, 7543 –
7551; b) A. Banerjee, Z. Lei, M.-Y. Ngai, Synthesis 2019, 51,
303 – 333; c) L. Revathi, L. Ravindar, W.-Y. Fang, K. P. Rakesh,
H.-L. Qin, Adv. Synth. Catal. 2018, 360, 4652 – 4698; d) X.
Zhang, D. W. C. MacMillan, J. Am. Chem. Soc. 2017, 139,
11353 – 11356; e) H. Yi, G. Zhang, H. Wang, Z. Huang, J. Wang,
A. K. Singh, A. Lei, Chem. Rev. 2017, 117, 9016 – 9085; f) S.
Tripathi, S. N. Singh, L. D. S. Yadav, Tetrahedron Lett. 2015, 56,
4211 – 4214; g) X.-H. Ouyang, R.-J. Song, C.-Y. Wang, Y. Yang,
J.-H. Li, Chem. Commun. 2015, 51, 14497 – 14500; h) J. Wang, C.
Liu, J. Yuan, A. Lei, Angew. Chem. Int. Ed. 2013, 52, 2256 – 2259;
Angew. Chem. 2013, 125, 2312 – 2315; i) C. Chatgilialoglu, D.
Crich, M. Komatsu, I. Ryu, Chem. Rev. 1999, 99, 1991 – 2069.
[22] For the coordination of boronic acid derivatives to N-nucleo-
philes followed by C-migration, see: a) K. Livingstone, J. Mowat,
C. Jamieson, S. Bertrand, Chem. Sci. 2019, 10, 10412 – 10416;
b) K. Livingstone, S. Bertrand, A. R. Kennedy, C. Jamieson,
Chem. Eur. J. 2020, 26, 10591 – 10597.
[
10] a) J. Ruan, O. Saidi, J. A. Iggo, J. Xiao, J. Am. Chem. Soc. 2008,
130, 10510 – 10511; b) J. K. Vandavasi, S. G. Newman, Synlett
2018, 29, 2081 – 2086; c) Z. Shi, N. Schroeder, F. Glorius, Angew.
Chem. Int. Ed. 2012, 51, 8092 – 8096; Angew. Chem. 2012, 124,
216 – 8220; d) T. Wakaki, T. Togo, D. Yoshidome, Y. Kuninobu,
8
[23] P. K. Prasad, R. N. Reddi, S. Arumugam, Org. Biomol. Chem.
2018, 16, 9334 – 9348.
M. Kanai, ACS Catal. 2018, 8, 3123 – 3128.
[
11] a) M. Pucheault, S. Darses, J.-P. Genet, J. Am. Chem. Soc. 2004,
[24] J. M. Concellon, H. Rodriguez-Solla, Curr. Org. Chem. 2008, 12,
524 – 543.
126, 15356 – 15357; b) G. Mora, S. Darses, J.-P. Genet, Adv.
Synth. Catal. 2007, 349, 1180 – 1184; c) C. Qin, J. Chen, H. Wu, J.
Cheng, Q. Zhang, B. Zuo, W. Su, J. Ding, Tetrahedron Lett. 2008,
[25] Y.-F. Chen, J. Chen, L.-J. Lin, G. J. Chuang, J. Org. Chem. 2017,
82, 11626 – 11630.
4
9, 1884 – 1888; d) P. ꢀlvarez-Bercedo, A. Flores-Gaspar, A.
[26] J. Takagi, K. Takahashi, T. Ishiyama, N. Miyaura, J. Am. Chem.
Soc. 2002, 124, 8001 – 8006.
[27] a) R. A. Batey, A. N. Thadani, D. V. Smil, A. J. Lough, Synthesis
2000, 990 – 998; See also: b) V. Ortega, A. G. Csaky, J. Org.
Chem. 2016, 81, 3917 – 3923.
[28] Similarly to the transformation reported herein, electron-rich
boronic acids are more reactive in Petasis-Mannich reactions.
See for example: a) M. Follmann, F. Graul, T. Schaefer, S.
Kopec, P. Hamley, Synlett 2005, 1009 – 1011; b) M. V. Shevchuk,
A. E. Sorochinsky, V. P. Khilya, V. D. Romanenko, V. P. Kukhar,
Synlett 2010, 73 – 76.
Correa, R. Martin, J. Am. Chem. Soc. 2010, 132, 466 – 467; e) M.
Kuriyama, N. Hamaguchi, K. Sakata, O. Onomura, Eur. J. Org.
Chem. 2013, 3378 – 3385; f) B. Suchand, G. Satyanarayana, J.
Org. Chem. 2016, 81, 6409 – 6423; g) Y.-X. Liao, Q.-S. Hu, J. Org.
Chem. 2010, 75, 6986 – 6989; h) H. Li, Y. Xu, E. Shi, W. Wei, X.
Suo, X. Wan, Chem. Commun. 2011, 47, 7880 – 7882; i) H. Zheng,
J. Ding, J. Chen, M. Liu, W. Gao, H. Wu, Synlett 2011, 1626 –
1630; j) C. Lei, D. Zhu, V. I. I. I. T. Tangcueco, J. S. Zhou, Org.
Lett. 2019, 21, 5817 – 5822; k) R. A. Swyka, W. G. Shuler, B. J.
Spinello, W. Zhang, C. Lan, M. J. Krische, J. Am. Chem. Soc.
2019, 141, 6864 – 6868.
[
12] a) P. Gandeepan, L. Ackermann, Chem 2018, 4, 199 – 222; b) A.
Ghosh, K. F. Johnson, K. L. Vickerman, J. A. Walker, L. M.
Stanley, Org. Chem. Front. 2016, 3, 639 – 644; c) M. C. Willis,
Hydroacylation of Alkenes, Alkynes, and Allenes Vol. 4, Elsevier,
Manuscript received: November 27, 2020
Revised manuscript received: December 30, 2020
Accepted manuscript online: January 21, 2021
Version of record online: March 5, 2021
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Angew. Chem. Int. Ed. 2021, 60, 8728 –8732