Cooperative Catalysis for the Highly Diastereo- and Enantioselective [4+3]-Cycloannulation of ortho-Quinone Methides and Carbonyl Ylides

Article abstract of DOI:10.1002/anie.201913603

We describe herein a highly diastereo- and enantioselective [4+3]-cycloannulation of ortho-quinone methides and carbonyl ylides to furnish functionalized oxa-bridged dibenzooxacines with excellent yields and stereoselectivity in a single synthetic step. The combination of rhodium and chiral phosphoric acid catalysis working in concert to generate both transient intermediates in situ provides direct access to complex bicyclic products with two quaternary and one tertiary stereogenic centers. The products may be further functionalized into valuable and enantiomerically highly enriched building blocks.

Full text of DOI:10.1002/anie.201913603

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Accepted Article
Title: Cooperative Catalysis for the Highly Diastereo- and
Enantioselective [4+3]-Cycloannulation of ortho-Quinone
Methides and Carbonyl Ylides
Authors: Christoph Schneider, Arun Suneja, and Henning Jakob Loui
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201913603
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10.1002/anie.201913603
Angewandte Chemie International Edition
COMMUNICATION
Cooperative Catalysis for the Highly Diastereo- and Enantioselec-
tive [4+3]-Cycloannulation of ortho-Quinone Methides and Car-
bonyl Ylides
Arun Suneja,[a] Henning Jakob Loui,[a] and Christoph Schneider*[a]
Dedicated to Professor Mark Lautens on the occasion of his 60th birthday
Abstract: We describe herein a highly diastereo- and enantioselec-
tive [4+3]-cycloannulation of ortho-quinone methides and carbonyl
ylides to furnish functionalized, oxa-bridged dibenzooxacines with
excellent yields and stereoselectivity in a single synthetic step. The
combination of rhodium and chiral phosphoric acid catalysis working
in concert to generate both transient intermediates in situ provides di-
rect access to complex bicyclic products with two quaternary and one
tertiary stereogenic centers. The products may be further functional-
due to the challenges associated with entropy factors and strain
aspects in the formation of seven-membered rings.[9, 10]
Ortho-quinone methides (o-QMs) feature a particularly reac-
tive 4-system and have increasingly been exploited as versatile
synthetic intermediates for the construction of complex heterocy-
cles.[11] In recent years, we and others have meticulously devel-
oped Brønsted acid-catalyzed reactions of o-QMs with a wide
range of typically 2π-nucleophiles leading to a broad range of
ized into valuable and enantiomerically highly enriched building blocks. benzannulated oxygen heterocycles with good to excellent stere-
ocontrol.[12, 13]
We now report the first cooperative, catalytic, enantioselective
Oxa‐bridged heterocyclic skeletons are ubiquitously present
[4+3]-cycloannulations of o-QMs and carbonyl ylides to afford
in numerous natural products and bioactive molecules.[1] There-
complex and enantiomerically highly enriched oxabicyclic
fore, the development of new, efficient, and stereoselective syn-
thetic methods towards their rapid construction are highly de-
sirable. Extensive efforts have previously been directed at carbo-
bridged bicyclic frameworks through Lewis-acid-catalyzed in-
dibenzooxacines. We envisioned that a chiral phosphoric acid
would easily form a hydrogen-bonded o-QMs A starting from or-
tho-hydroxy benzylalcohol 1 in one catalytic cycle while in a se-
cond and separate catalytic cycle a carbonyl ylide B was genera-
tramolecular Diels-Alder (IMDA) reactions, molecular rearrange-
ted via Rh-catalyzed decomposition of a -diazoester 2 tethered
ments involving ring-opening/closure tandem process, free-radi-
to an aryl ketone (Scheme 1). The decisive question here was
cal reactions, and transition-metal catalyzed annulation reac-
whether both transient intermediates A and B formed in only ca-
talytic amounts would have the sufficient stability and lifetime to
undergo the desired [4+3]-cycloannulation and provide the pro-
duct 3 with good stereocontrol in the chiral environment provided
tions.[2] However, there still remains a high demand for the syn-
thesis of oxa‐bridged heterocycles.[3]
The combination of a transition metal catalyst and a Lewis a-
cid or organocatalyst to activate two different substrates for a
by the phosphoric acid catalyst.
given reaction has attracted significant interest among synthetic
organic chemists recently as it potentially enables highly efficient
and/or unprecedented complex chemical transformations in a
one-pot operation.[4] The success of this strategy relies upon the
simultaneous activation of two reacting partners by two different
catalysts that operate in concert in two distinct catalytic cycles.[4c]
A prominent early example in this respect constitutes the work of
Hu and Gong on cooperative Rh-/chiral phosphoric acid catalyzed
multicomponent reactions of α-diazoesters, amines or alcohols,
and imines which were converted into -functionalized -amino
esters with excellent enantio- and diastereocontrol.[5] In another
example, Terada et al. developed an elegant carbonyl ylide for-
mation/reduction-sequence towards isochromanones under
cooperative Rh-/chiral phosphoric acid catalysis.[6]
Carbonyl ylides generated from carbonyl compounds and a
rhodium carbene complex are classically considered as highly re-
active transient species and are widely employed in 1,3-dipolar
Scheme 1. Design plan for the reaction between o-QMs and carbonyl ylides
via cooperative Rh-/phosphoric acid-catalysis.
8]
cycloaddition reactions with a wide variety of 2π-systems.[7,
However, their reactivity with 4π-systems is still underexplored
Enantioselective [4+3]-cycloadditions of o-QMs have first
been described independently by Scheidt and Ye under chiral
NHC catalysis to produce benzoxopinones.[14a, b] Very recently,
the first example of a phosphoric acid-catalyzed enantioselective
reaction of o-QMs with 2-indolylmethanols as 1,3-dipoles toward
indolylbenzoxepins has been established by Shi et al.[14c] An inte-
resting study of the Lautens group described a purely Brønsted
[a]
Dr. A. Suneja, MSc. H. J. Loui, Prof. Dr. C. Schneider
Institut für Organische Chemie, Universität Leipzig
Johannisallee 29, 04103 Leipzig (Germany)
E-mail: schneider@chemie.uni-leipzig.de
Supporting information for this article can be found under:
http://dx.doi.org/.
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10.1002/anie.201913603
Angewandte Chemie International Edition
COMMUNICATION
acid-catalyzed, diastereoselective synthesis of oxa-bridged o-
xazocines via cycloaddition with isomünchnones.[14e]
2a-k was tested with benzhydryl alcohol 1a as model ortho-
quinone methide precursor. Pleasingly, the reaction worked well
with all substrates and afforded products 3a-k in good to excellent
yields and excellent enantioselectivities of up to 97:3 e.r. (Scheme
2). The diastereoselectivity appeared to be dependent on the
electronic character of the aryl substituent with electronrich aryl
groups generally giving rise to almost perfect selectivity. In parti-
cular, the thiophene-substituted diazoester 2k gave rise to pro-
duct 3k with 92% yield as a single diastereomer and with 95:5 e.r.
On the other hand, substrates 2g-j carrying electron-poor substi-
tuents (such as halogen and CF3-groups) furnished products 3g-
j with diminished diastereoselectivity, albeit in excellent yields and
up to 96:4 e.r. Ortho-substituted aryl groups had a detrimental
effect on both the diastereo- and enantioselectivity as documen-
ted for 3e (6:1 d.r., 89:11 e.r.) most probably for steric reasons.
Most importantly, this cycloannulation is not limited to aryl- and
heteroaryl-substituted diazoketones but could be extended to an
alkyl-substituted substrate as well. Thus, dibenzooxacine 3l was
obtained in high yield and stereoselectivity similar to the other pro-
ducts.
To test our hypothesis, we initiated our investigations with the
model reaction between benzhydryl alcohol 1a and α-diazoester
2a in the presence of 5 mol% of Rh2(OAc)4 and chiral phosphoric
acid PA1 (10 mol%) in CHCl3 at room temperature. We were de-
lighted to obtain the desired product 3a in 77% yield after 12 h
with moderate diastereo- and enantioselectivity (Table 1, entry 1).
Importantly, diazoester 2a had to be added slowly for a period of
1 h using a syringe pump to avoid side reactions of the transient
carbonyl ylide.
Table 1: Catalyst screening and optimization studies.[a]
entry
PA
solvent
time
[h]
3a
er[d]
dr[e]
(%)[b,c]
1
2
1
2
3
4
5
6
7
7
7
7
7
7
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
1,2-DCE
PhMe
12
12
12
12
12
12
12
12
12
48
48
12
77
71
66:34
82:18
69:31
83:17
84:16
88:12
92:8
16:1
20:1
10:1
20:1
20:1
20:1
20:1
20:1
15:1
8:1
3
75
4
79
5
80
6
73
7
79
8
83
83:17
83:17
85:15
ND
9
75
10
11
12f
58
CPME
CHCl3
trace
96
ND
96:4
20:1
aReactions were carried out with 0.10 mmol of 1a, 0.11 mmol of 2a and
Rh2(OAc)4 (5 mol %) in the presence of catalyst PA (10 mol %) in CHCl3 (3
mL). bIsolated yield of both diastereomers after chromatographic purifica-
tion. cDecomposition accounts for remainder of mass balance.
dEnantiomeric ratios (e.r.) were determined by chiral HPLC. eDiastereo-
meric ratios (d.r.) were determined from 1H NMR of crude reaction mixture.
f With 3 Å MS (35 mg).
Extensive screening of suitable chiral phosphoric acid cata-
lysts[15] revealed that Rh2(OAc)4 (5 mol%) and 10 mol% of (R)-
PA7 provided the best combination, which afforded 3a in 79%
yield with 20:1-diastereoselectivity and with 92:8 e.r. (entry 7). A
short study of reaction conditions revealed CHCl3 to be the sol-
vent of choice and that both chemical yield and enantioselectivity
were further improved by using 3 Å molecular sieves (MS) as de-
hydrating agent. Thus, using these conditions 3a was eventually
obtained in 96% yield with 20:1-diastereoselectivity and with 96:4
e.r. (entry 12). Interestingly, lowering the catalyst loading of
Rh2(OAc)4 and (R)-PA7 did not deteriorate the enantiomeric ratio,
but led to a decrease in the diastereoselectivity of the product (see
the Supporting Information for more details).
Scheme 2. Substrate scope for reactions of ortho-hydroxy benzhydryl alcohol
1a with various α-diazoesters 2a-l. aReactions were carried out with 0.1 mmol
of 1a, 0.11 mmol of 2, 3 Å MS (35 mg) and Rh2(OAc)4 (5 mol %) in the presence
of catalyst PA7 (10 mol %) in CHCl3 (3 mL).
With optimized conditions in hand, we set out to examine the
substrate scope of the reaction. Initially, a series of α-diazoesters
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COMMUNICATION
We then turned our attention to reactions of α-diazoester 2a
with various substituted o-hydroxy benzhydryl alcohols 1 as ortho-
quinone methide precursors (Scheme 3). Gratifyingly, a broad va-
riety of substrates with both electron-donating as well as electron-
withdrawing in the o-QM component were readily converted into
products 4a-n at slightly elevated temperature. Yields ranged
from moderate to excellent and the diastereo- and enantioselec-
tivity was generally very high. Here again, a dependance of reac-
tion outcome on the electronic character of the substrates was
observed. Whereas electron-rich benzhydryl alcohols furnished
products with very good yields (e.g. 4a-4f), electron-poor substra-
tes afforded products with only moderate chemical yield, albeit
excellent enantioselectivity (e.g. 4g and 4h).
benzhydryl alcohol 1o failed to deliver product 4o because the
transient o-QM generated in situ from 1o apparently was too un-
stable to successfully engage the transient carbonyl ylide in the
cycloannulation event. The X-ray structure analysis of the major
diastereomer of product 3k confirmed both the relative and abso-
lute configuration which was assigned to all other products ac-
cordingly (Figure 1).[16, 17]
Figure 1: X-ray crystal structure of product 3k.[16]
To gain more insight into the mechanism of this cycloannu-
lation process some control experiments were conducted. Under
the standard conditions O-methyl protected benzhydryl alcohol 1p
failed to react with 2a underlining the importance of the o-QM
structure for this reaction (Scheme 4, eq. 1). Furthermore, neither
in the presence of the phosphoric acid alone with Rh2(OAc)4 ab-
sent (case A) nor in the presence of Rh2(OAc)4 alone with the
phosphoric acid absent (case B) was a successful reaction obser-
ved (eq. 2). We therefore conclude that both catalysts actively
participate in this reaction by generating both the o-QM and the
carbonyl ylide as transient intermediates. These control experi-
ments strongly support our initial reaction design of a cooperative
catalytic activation of both nucleophile and electrophile in a one-
pot process.
Scheme 3. Expansion of substrate scope for reaction of various ortho-hydroxy
benzhydryl alcohol 1 with α-diazoester 2a. aReactions were carried out with 0.1
mmol of 1, 0.11 mmol of 2a, 3 Å MS (35 mg) and Rh2(OAc)4 (5 mol %) in the
presence of catalyst PA7 (10 mol %) in CHCl3 (3 mL).
Structural variation in the quinone moiety was more readily
tolerated irrespective of the electronic character. Thus, products
4j-4n with alkyl and various halogen substituents were obtained
with synthetically useful yields and very good diastereo- and en-
antioselectivity (Scheme 3). Unfortunately, the iPr-substituted
Scheme 4. Control experiments.
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COMMUNICATION
In order to further shine light on the origin of enantioselecti-
vity we conducted reactions of 1a and 2a in the presence of a
chiral rhodium catalyst and both an achiral and a chiral phosphoric
acid (Scheme 4, eq. 3). Whereas the enantioselectivity of the lat-
ter reaction was virtually unchanged in comparison to the reaction
with Rh2(OAc)4 reported above, no enantioselectivity was obser-
ved with diphenyl phosphate as Brønsted acid catalyst. Moreover,
reaction of the stable ortho-quinone methide 1q and 2a in the
presence of the chiral rhodium catalyst alone delivered dibenzoo-
xacine 4q in low yield and as a racemic mixture indicating once
again the critical role of the chiral phosphoric acid for the enanti-
oselectivity of the process (eq. 4).
Acknowledgements
This work was generously supported by the Deutsche For-
schungsgemeinschaft (SCHN 441/11-2) and through gifts of
chemicals from BASF and Evonik. We thank Dr. M. Schlegel for
helpful discussions and Dr. P. Lӧnnecke (both University of Leip-
zig) for solving the X-ray crystal structure.
Conflict of interest
The authors declare no conflict of interest.
Finally, we attempted some structural modifications of the
products and identified the acetal moiety of 3a as a good starting
point for further synthetic elaborations. Under BF3-activation the
acetal was readily cleaved to the corresponding oxonium ion
which was trapped with allyltributylstannane to furnish isobenzo-
furan 5 with good yield and complete diastereocontrol. Phenol 5
was then lactonized with p-TsOH to produce the highly congested
spirocyclic dihydrocoumarin 6 again with good yield (Scheme 5).
The product 6 was thus obtained in 72% yield over two steps as
a single diastereomer and with 98:2 e.r. On the other hand, the
oxa-bridged products 3 are sufficiently stable as to easily tolerate
further post-modifications such as a Suzuki-Miyaura cross cou-
pling reaction which proceeded in very good yield in the case of
3i.
Keywords: asymmetric synthesis • carbonyl ylides • cycloannu-
lation • ortho-quinone methides • cooperative catalysis
[1]
a) Y. Li, M. Dai, Angew. Chem. Int. Ed. 2017, 56, 11624; Angew. Chem.
2017, 129, 11782; b) R. C. Jadulco, C. D. Pond, R. M. Van Wagoner, M.
Koch, O. G. Gideon, T. K. Matainaho, P. Piskaut, L. R. Barrows, J. Nat.
Prod. 2014, 77, 183.
[2]
[3]
a) W. Zhao, Chem. Rev. 2010, 110, 1706; b) Z. Yin, Y. He, P. Chiu,
Chem. Soc. Rev. 2018, 47, 8881.
J. Zhang, Z. Liao, L. Chen, S. Zhu, Chem. Eur. J. 2019, 25, 9405; b) J.
Zhang, Z. Liao, L. Chen, H. Jiang, S. Zhu, Chem. Commun. 2019, 55,
7382.
[4]
Selected reviews: a) M. H. Wang, K. A. Scheidt, Angew. Chem. Int. Ed.
2016, 55, 14912; Angew. Chem. 2016, 128, 15134; b) S. Afewerki, A.
Cꢀrdova, Chem. Rev. 2016, 116, 13512; b) Y. Deng, S. Kumar, H. Wang,
Chem. Commun. 2014, 50, 4272; b) H. Pellissier, Tetrahedron 2013, 69,
7171; c) X. Guo, W. Hu, Acc. Chem. Res. 2013, 46, 2427; d) Z. Du, Z.
Shao, Chem. Soc. Rev. 2013, 42, 1337; e) A. E. Allen, D. W. C. MacMil-
lan, Chem. Sci. 2012, 3, 633; d) R. C. Wende, P. R. Schreiner, Green
Chem. 2012, 14, 1821.
[5]
[6]
[7]
a) W. H. Hu, X. F. Xu, J. Zhou, W. J. Liu, H. X. Huang, J. Hu, L. P. Yang,
L. Z. Gong, J. Am. Chem. Soc. 2008, 130, 7782.
M. Terada, Y. Toda, Angew. Chem. Int. Ed. 2012, 51, 2093; Angew.
Chem. 2012, 124, 2134.
a) M. Petzold, P. J. Jones, D. B. Werz, Angew. Chem. Int. Ed. 2019, 58,
6225; Angew. Chem. 2019, 131, 6291; b) Q. Q. Cheng, M. Lankelma, D.
Wherritt, H. Arman, M. P. Doyle, J. Am. Chem. Soc. 2017, 139, 9839; c)
A. G. Smith, H. M. L. Davies, J. Am. Chem. Soc. 2012, 134, 18241; d) X.
Hong, S. France, A. Padwa, Tetrahedron 2007, 63, 5962; e) M. P. Doyle,
M. A. McKervey, T. Ye, Modern Catalytic Methods for Organic Synthesis
with Diazo Compounds, Wiley, New York, 1998.
Scheme 5. Synthetic elaborations of oxa-bridged dibenzooxacines 3.
[8]
[9]
a) S. A. Bonderoff, A. Padwa, J. Org. Chem. 2017, 82, 642; b) H. Li, S.
A. Bonderoff, B. Cheng, A. Padwa, J. Org. Chem. 2014, 79, 392; c) M.
P. Doyle, R. J. Pieters, J. Taunton, H. Q. Pho, A. Padwa, D. L. Hertzog,
L. Precedo, J. Org. Chem. 1991, 56, 820.
In conclusion, we have developed a novel and highly stere-
oselective [4+3]-cycloannulation of transient carbonyl ylides with
in situ generated o-QMs via cooperative Rh-/phosphoric acid ca-
talysis. The reaction comprises the catalytic enantio- and dia-
stereoselective synthesis of oxa-bridged heterocycles featuring
two quaternary and one tertiary stereogenic centers in a one-pot
operation. The benzannulated O-heterocycles were obtained in
typically high yields (up to 96%) and excellent stereoselectivities
(up to >20:1 d.r. and up to 97:3 e.r.). Moreover, the products may
be successfully manipulated to access valuable synthetic building
blocks. The striking feature of this process is the separate cata-
lytic activation of nucleophile and electrophile with a chiral phos-
phoric acid enabling the formation of a transient hydrogen-bonded
ortho-quinone methide and Rh2(OAc)4 delivering the transient car-
bonyl ylide in a one-pot operation. Further extensions of this pro-
cess are currently underway in our laboratory.
Selected reviews on [4+3]-cycloadditions: a) A. G. Lohse, R. P. Hsung,
Chem. Eur. J. 2011, 17, 3812; b) M. Harmata, Chem. Commun. 2010,
46, 8904.
[10] Selected recent examples of [4+3]-cycloadditions: a) H. Xu, J.-L. Hu, L.
Wang, S. Liao, Y. Tang, J. Am. Chem. Soc. 2015, 137, 8006; b) H. Shang,
Y. Wang, Y. Tian, J. Feng, Y. Tang, Angew. Chem. Int. Ed. 2014, 53,
5662; Angew. Chem. 2014, 126, 5768; c) B. D. Schwartz, J. R. Denton,
Y. Lian, H. M. L. Davies, C. M. Williams, J. Am. Chem. Soc. 2009, 131,
8329; d) R. P. Reddy, H. M. L. Davies, J. Am. Chem. Soc. 2007, 129,
10312.
[11] For representative reviews on o-OMs: a) C. D. T. Nielsen, H. Abas, A. C.
Spivey, Synthesis 2018, 50, 4008; b) B. Yang, S. Gao, Chem. Soc. Rev.
2018, 47, 7926; c) A. A. Jaworski, K. A. Scheidt, J. Org. Chem. 2016, 81,
10145; d) L. Caruana, M. Fochi, L. Bernardi, Molecules 2015, 20, 11733;
e) Z. Wang, J. Sun, Synthesis 2015, 47, 3629; f) W.-J. Bai, J. G. David,
Z.-G. Feng, M. G. Weaver, K.-L. Wu, T. R. R. Pettus, Acc. Chem. Res.
2014, 47, 3655; g) N. J. Willis, C. D. Bray, Chem. Eur. J. 2012, 18, 9160;
h) T. P. Pathak, M. S. Sigman, J. Org. Chem. 2011, 76, 9210.
This article is protected by copyright. All rights reserved.

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COMMUNICATION
[12] From our group: a) R. Ukis, C. Schneider, J. Org. Chem. 2019, 84, 7175;
b) A. Suneja, C. Schneider, Org. Lett. 2018, 20, 7576; c) F. Gӧricke, C.
Schneider, Angew. Chem. Int. Ed. 2018, 57, 14736; Angew. Chem. 2018,
130, 14952; d) M. Spanka, C. Schneider, Org. Lett. 2018, 20, 4769; e) K.
Gebauer, F. Reuß, M. Spanka, C. Schneider, Org. Lett. 2017, 19, 4588;
f) S. K. Alamsetti, M. Spanka, C. Schneider, Angew. Chem. 2016, 128,
2438; Angew. Chem. Int. Ed. 2016, 55, 2392; g) S. Saha, S. K. Alamsetti,
C. Schneider, Chem. Commun. 2015, 51, 1461; h) S. Saha, C. Schneider,
Org. Lett. 2015, 17, 648; i) S. Saha, C. Schneider, Chem. Eur. J. 2015,
21, 2348; j) O. El-Sepelgy, S. Haseloff, S. K. Alamsetti, C. Schneider,
Angew. Chem. 2014, 126, 8057; Angew. Chem. Int. Ed. 2014, 53, 7923.
[13] From other groups, see: (a) F. Jiang, K.-W. Chen, P. Wu, Y.-C. Zhang,
Y. Jiao, F. Shi, Angew. Chem. Int. Ed. 2019, 58, 15104; Angew. Chem.
2019, 131, 15248; (b) R. P. Pandit, S. T. Kim, D. H. Ryu, Angew. Chem.
Int. Ed. 2019, 58, 13427; Angew. Chem. 2019, 131, 13561; (c) C. D.
Gheewala, J. S. Hirschi, W.-H. Lee, D. W. Paley, M. J. Vetticatt, T. H.
Lambert, J. Am. Chem. Soc. 2018, 140, 3523; (d) H. J. Jeong, D. Y. Kim,
Org. Lett. 2018, 20, 2944; (e) Y. Xie, B. List, Angew. Chem. Int. Ed. 2017,
56, 4936; Angew. Chem. 2017, 129, 5018; (f) J.-L. Wu, J.-Y. Wang, P.
Wu, G.-J. Mei, F. Shi, Org. Chem. Front. 2017, 4, 2465; (g) Z. Wang, J.
Sun, Org. Lett. 2017, 19, 2334; (h) C. Gharui, S. Singh, S. C. Pan, Org.
Biomol. Chem. 2017, 15, 7272; (i) M.-M. Xu, H.-Q. Wang, Y. Wan, G. He,
J. Yan, S. Zhang, S.-L. Wang; F. Shi, Org. Chem. Front. 2017, 4, 358; (j)
X.-Y. Yu, J.-R. Chen, Q. Wei, H.-G. Cheng, Z.-C. Liu, W.-J. Xiao, Chem.
Eur. J. 2016, 22, 6774; (k) Y.-C. Zhang, Q.-N. Zhu, X. Yang, L.-J. Zhou,
F. Shi, J. Org. Chem. 2016, 81, 1681; (l) Z. Lai, J. Sun, Synlett 2016, 27,
555; (m) J.-J. Zhao, Y.-C. Zhang, M.-M. Xu, M. Tang, F. Shi, J. Org.
Chem. 2015, 80, 10016; (n) G. C. Tsui, L. Liu, B. List, Angew. Chem. Int.
Ed. 2015, 54, 7703; Angew. Chem. 2015, 127, 7814; (o) H. Hu, Y. Liu, J.
Guo, L. Lin, Y. Xu, X. Liu, X. Feng, Chem. Commun. 2015, 51, 3835; (p)
W. Zhao, Z. Wang, B. Chu, J. Sun, Angew. Chem. Int. Ed. 2015, 54,
1910; Angew. Chem. 2015, 127, 1930; (q) J.-J. Zhao, S.-B. Sun, S.-H.
He, Q. Wu, F. Shi, Angew. Chem. Int. Ed. 2015, 54, 5460; Angew. Chem.
2015, 127, 5550; (r) Z. Wang, F. Ai, Z. Wang, W. Zhao, G. Zhu, Z. Lin, J.
Sun, J. Am. Chem. Soc. 2015, 137, 383; (s) C.-C. Hsiao, S. Raja, H.-H.
Liao, I. Atodiresei, M. Rueping, Angew. Chem., Int. Ed. 2015, 54, 5762;
Angew. Chem. 2015, 127, 5854; (t) Z. Lai, Z. Wang, J. Sun, Org. Lett.
2015, 17, 6058; (u) C.-C. Hsiao, H.-H. Liao, M. Rueping, Angew. Chem.,
Int. Ed. 2014, 53, 13258; Angew. Chem. 2014, 126, 13474; (v) M.
Rueping, U. Uria, M. Y. Lin, I. Atodiresei, J. Am. Chem. Soc. 2011, 133,
3732; (w) D. Wilcke, E. Herdtweck, T. Bach, Synlett 2011, 1235.
[14] For recent enantioselective [4+3]-cycloannulations of o-QMs: with chiral
NHC catalysis: a) J. Izquierdo, A. Orue, K. A. Scheidt, J. Am. Chem. Soc.
2013, 135, 10634; b) H. Lv, W.-Q. Jia, L.-H. Sun, S. Ye, Angew. Chem.
Int. Ed. 2013, 52, 8607; Angew. Chem. 2013, 125, 8769; with chiral phos-
phoric acid catalysis: c) M. Sun, C. Ma, S.-J. Zhou, S.-F. Lou, J. Xiao, Y.
Jiao, F. Shi, Angew. Chem. Int. Ed. 2019, 58, 8703; Angew. Chem. 2019,
131, 8795; for catalytic, non-enantioselective reactions see: d) J.-Y. Du,
Y.-H. Ma, F.-X. Meng, R.-R. Zhang, R.-N. Wang, H.-L. Shi, Q. Wang, Y.-
X. Fan, H.-L. Huang, J.-C. Cui, C.-L. Ma Org. Lett. 2019, 21, 465; e) H.
Lam, Z. Qureshi, M. Wegmann, M. Lautens, Angew. Chem. Int. Ed. 2018,
57, 16185; Angew. Chem. 2018, 130, 16417; f) for a related process not
involving o-QMs that appeared during the revision of this manuscript see:
C. R. Xu, K. X. Wang, D. W. Li, L. L. Lin, X. M. Feng, Angew. Chem. Int.
Ed. 2019, 58, 18438; Angew. Chem. 2019, 131, 18609; g) G.-J. Mei, Z.-
Q. Zhu, J.-J. Zhao, C.-Y. Bian, J. Chen, R.-W. Chen, F. Shi, Chem. Com-
mun. 2017, 53, 2768; h) J. Xu, S. Yuan, J. Peng, M. Miao, Z. Chen, H.
Ren, Org. Biomol. Chem. 2017, 15, 7513.
[15] Selected reviews: a) F. E. Heldt, D. Grau, S. B. Tsogoeva, Molecules
2015, 20, 16103; b) D. Parmar, E. Sugiono, S. Raja, M. Rueping, Chem.
Rev. 2014, 114, 9047; c) A. A. Desai, W. D. Wulff, Synthesis 2010, 3670;
d) D. Kampen, C. M. Reisinger, B. List, Top. Curr. Chem. 2010, 291, 395;
e) A. Zamfir, S. Schenker, M. Freund, S. B. Tsogoeva, Org. Biomol.
Chem. 2010, 8, 5262; f) M. Terada, Synthesis 2010, 12, 1929; g) T. Aki-
yama, Chem. Rev. 2007, 107, 5744.
[16] CCDC 1946746 (3k) contains the supplementary crystallographic data
for this paper. These data are provided free of charge by The Cambridge
Crystallographic Data Centre.
[17] We assume a similar transition state assembly in this reaction as in pre-
vious examples of phosphoric acid-catalyzed reactions of ortho-quinone
methides (see e. g. ref. 12j) based upon the identical absolute configura-
tion of the products.
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10.1002/anie.201913603
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Arun Suneja, Henning J. Loui, and
Christoph Schneider*
Page No. – Page No.
Cooperative Catalysis for the Highly
Diastereo- and Enantioselective [4+3]-
Cycloannulation of ortho-Quinone
Methides and Carbonyl Ylides
A combination of Rh2(OAc)4 and a chiral phosphoric acid catalyzed the highly
diastereo- and enantioselective reaction of transient carbonyl ylides and ortho-
quinone methides both in situ generated in cooperative catalytic cycles to afford a
broad range of functionalized, oxa-bridged dibenzooxacines featuring two quaternary
and one tertiary stereogenic centers.
This article is protected by copyright. All rights reserved.