Palladium-Catalyzed Asymmetric (2+3) Annulation of p-Quinone Methides with Trimethylenemethanes: Enantioselective Synthesis of Functionalized Chiral Spirocyclopentyl p-Dienones

Article abstract of DOI:10.1021/acs.orglett.0c01252

A novel asymmetric catalytic (2+3) annulation of p-quinone methides with CN-substituted trimethylenemethane is described under palladium catalysis, providing an alternative approach for the enantioselective construction of highly functionalized chiral spirocyclopentyl p-dienones. Driven by the significant improvement in the reactivity and enantioselectivity, a novel type of non-C2-symmetric phosphoramidite ligand from the chirality-matched combination of (S)-BINOL and sterically demanding amine derived from l-hydroxyproline is evolved and explored for the protocol presented here.

Full text of DOI:10.1021/acs.orglett.0c01252

pubs.acs.org/OrgLett
Letter
Palladium-Catalyzed Asymmetric (2+3) Annulation of p‑Quinone
Methides with Trimethylenemethanes: Enantioselective Synthesis of
Functionalized Chiral Spirocyclopentyl p‑Dienones
Zhi-Long Jia, Xian-Tao An, Yu-Hua Deng, Hui-Bin Wang, Kang-Ji Gan, Jing Zhang, Xian-He Zhao,*
and Chun-An Fan*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01252
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A novel asymmetric catalytic (2+3) annulation of p-
quinone methides with CN-substituted trimethylenemethane is
described under palladium catalysis, providing an alternative
approach for the enantioselective construction of highly function-
alized chiral spirocyclopentyl p-dienones. Driven by the significant
improvement in the reactivity and enantioselectivity, a novel type
of non-C2-symmetric phosphoramidite ligand from the chirality-
matched combination of (S)-BINOL and sterically demanding
amine derived from L-hydroxyproline is evolved and explored for
the protocol presented here.
he spirocyclopentyl p-dienone unit A (spiro[4.5]deca-
6,9-dien-8-one), which is generally characterized by the
Scheme 1. Known Catalytic Asymmetric Approaches to
Spirocyclopentyl p-Dienones and Our Design
T
spirocyclic 2,5-cyclohexadienone ring system, widely exists in
biologically active natural products (Figure 1),1 and its
Figure 1. Selected natural products containing the spirocyclopentyl p-
dienone unit.
functionalized building blocks also serve as versatile
intermediates for natural product synthesis.2 Due to its unique
molecular architecture and considerable potential in organic
synthesis, the catalytic asymmetric construction of such a
structural unit has attracted significant interest from the
synthetic community. As shown in Scheme 1, several elegant
works on the enantioselective establishment of spirocyclopen-
tyl unit A have been previously published, including Rh-
Received: April 8, 2020
https://dx.doi.org/10.1021/acs.orglett.0c01252
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
catalyzed intramolecular asymmetric enyne cyclization of
substituted p-dienone precursors by Nicolaou (route a),2 Pd-
and Ir-catalyzed intramolecular asymmetric dearomatizing
cyclization of phenol precursors by You,3a Hamada,3c and
Buchwald3b (route b), Pd-catalyzed dearomatizing (3+2)
annulation of biaryl precursors with alkynes or 1,3-dienes by
Luan (route c),4 and Pd-catalyzed asymmetric (2+3)
annulation of p-quinone methides (p-QMs) with charged−
isolated C3 synthon (I) generated in situ from vinyl
cyclopropanes (VCPs) by Zhao (route d).5 Despite much
recent progress on this topic, the development of an alternative
catalytic asymmetric methodology for the diversity-oriented
synthesis of functionalized spirocyclopentyl p-dienones is still
highly appealing.
Table 1. Optimization of Reaction Conditions
The chemistry of p-quinone methides (p-QMs) featuring a
unique bisvinylogous enone system has received a great deal of
attention over the past decade in asymmetric catalysis.6−10
Compared with its intensive investigations, mostly focusing on
enantioselective 1,6-conjugate addition9 and (4+2) annula-
tion,10 however, the design of catalytic asymmetric (3+2)
annulation of p-QMs has been explored rarely.5 In connection
with our continuing interest in the chemistry of p-QMs,8,11
together with the importance of structurally divergent
functionalized spirocyclopentyl p-dienones, a strategically
alternative regio- and stereoselective (2+3) annulation of p-
QMs with a charged−delocalized C3 synthon [II and III
(Scheme 1)] formed in situ from substituted trimethylene-
methanes (TMMs)12−16 has been developed under palladium
catalysis, in which a novel type of non-C2-symmetric chiral
phosphoramidite ligands containing the BINOL backbone and
hydroxyproline moiety has been produced to explore the
pivotal stereoselectivities (enantio- and diastereo-) as well as
the regioselectivity (α,γ vs γ,γ′). This novel annulation reaction
provides an effective method for the diastereo- and
enantioselective synthesis of multifunctionalized spirocyclo-
pentyl p-dienones. Herein, we report our results on this
subject.
Initially, as shown in Table 1, the model reaction for the
designed asymmetric (2+3) annulation was investigated by
using p-QM 1a as a two-carbon synthon and racemic cyano-
substituted trimethylenemethane (CN-TMM) 2a17,18 as a
three-carbon synthon in the presence of Pd(dba)2 as a catalyst
and toluene as a solvent19 at room temperature. Compared
with the inefficiency of (R)-BINAP as a typical bisphosphine
ligand (entry 1), using C2-symmetric (S)-BINOL-based
phosphoramidite L1 (entry 2) delivered the desired annulation
adduct 3aa with a promising stereoselectivity (75% ee, >20:1
dr), albeit in a modest yield of 13%. Interestingly, the
employment of the monodentate phosphoramidite L2 having a
bulky (S)-CH(Me)Ph substituent (entry 3) led to a
substantially increased yield (70%) and stereoselectivity
(94% ee, >20:1 dr). Notably, phosphoramidite L3 with a less
bulky methyl group (entry 4) was ineffective in this model
reaction. In addition to these phosphoramidite ligands with
acyclic amino moieties (L1−L3), a series of phosphoramidites
L4−L9 having structurally modified cyclic pyrrolidinyl motifs
were further investigated in this case. No reaction was
observed when phosphoramidites L4−L6 with a less sterically
hindered pyrrolidinyl ring system were employed (entries 5−7,
respectively). In contrast to the nonreactivity observed in the
cases using L-proline-derived phosphoramidites L5 (R1 = H, R2
= CO2Me, entry 6) and L6 (R1 = H, R2 = CH2OMe, entry 7),
it is noteworthy that the same chiral framework-based ligand
b
c
d
entry
ligand
additive
t (h) yield (%)
dr
ee (%)
e
1
2
3
4
5
6
7
8
(R)-BINAP
12
12
1
12
12
12
12
1
NR
13
70
−
−
75
94
−
−
−
L1
L2
L3
L4
L5
L6
L7
L8
L9
L8
L8
L8
>20:1
>20:1
−
−
−
e
NR
e
e
e
NR
NR
NR
−
−
69
72
50
77
92
80
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
98
99
99
99
99
99
9
0.5
10
11
12
13
1.2
0.5
0.5
0.5
Na2CO3
K2CO3
Cs2CO3
a
Unless otherwise noted, the reaction was performed with 1a (0.1
mmol), 2a (0.2 mmol), Pd(dba)2 (0.005 mmol), and ligand (0.01
mmol) under an argon atmosphere in the presence of an additive (0.1
mmol) in toluene (1.0 mL) at room temperature. Isolated yield.
Determined by H NMR. Determined by chiral HPLC analysis.
No reaction.
b
c
d
1
e
L7 [R1 = H, R2 = C(Ph)2OMe, entry 8] bearing a sterically
congested tertiary substituent gave a good yield (69%) and
high stereoselectivity (98% ee, >20:1 dr), showing the
somewhat increasing steric demand of the phosphoramidite
ligand. Accordingly, two novel sterically enhanced phosphor-
amidites L8 [R1 = OTBS, R2 = C(Ph)2OMe, entry 9] and L9
[R1 = OTBDPS, R2 = C(Ph)2OMe, entry 10], which were
derived from readily available L-hydroxyproline, were then
evaluated, and gratifyingly, OTBS-substituted L8 gave a better
result (0.5 h, 72% yield, 99% ee, >20:1 dr) (entry 9). With an
attempt to further improve the reaction reactivity, some
inorganic bases were examined (entries 11−13). Among them,
the model reaction utilizing K2CO3 as an additive in the
presence of L8 could deliver the optimal result in 92% yield
with a 99% ee and a >20:1 dr (entry 12).
With the optimal conditions in hand, as shown in Scheme 2,
the generality of the asymmetric catalytic (2+3) annulation
reaction was explored by using a series of p-QMs bearing
different aromatic Rb group at their δ position. In general, the
desired spirocyclic products could be afforded in good yields
(56−95%) with excellent stereoselectivities (>20:1 dr, 99%
ee). For example, p-QMs with electron-deficient (1b−1f and
1i), electron-rich (1g, 1h, 1j, 1k, and 1n), or electron-neutral
(1a) aromatic Rb groups at the meta and para positions were
well tolerated, and the corresponding spirocyclic products
3aa−3ka and 3na were obtained in excellent stereoselectivities
B
https://dx.doi.org/10.1021/acs.orglett.0c01252
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
To explore the practical utility of this protocol, as
demonstrated in Scheme 3, the gram-scale reaction of 1a
Scheme 2. Generality of the Asymmetric Catalytic (2+3)
Annulation
Scheme 3. Gram-Scale Reaction and Its Isomerization
and 2a was performed under the standard conditions, and the
desired spiroannulated product 3aa was obtained in high yield
(89%) and excellent stereoselectivity (>20:1 dr, 99% ee). In an
attempt to increase the structural diversity of chiral
spirocyclopentyl p-dienones, the treatment of 3aa with DBU
in toluene at 80 °C resulted in an effective isomerization of the
exocyclic double bond to the thermodynamically stable
endocyclic double bond, giving 3ab in 99% yield and 99% ee.
According to the aforementioned experimental results and
literature reports,16b,17,21 a rational mechanism is proposed for
the present Pd-catalyzed (2+3) annulation reaction of p-QM
1a with CN-TMM precursor 2a (Scheme 4). Initially, 2a is
Scheme 4. Proposed Mechanism
(>20:1 dr, 99% ee) and moderate to good yields (66−95%). In
addition, the absolute configuration of 3da was unambiguously
established by X-ray crystallographic analysis.20 While using p-
QMs 1l and 1m with sterically bulky ortho substituents,
notably the reactions proceeded smoothly to afford the
expected products 3la (88% yield, 99% ee) and 3ma (95%
yield, 99% ee), respectively.
In addition, the heteroaryl p-QMs 1o (Rb = 2-furyl) and 1p
(Rb = 2-pyridinyl) were also exposed to the optimized
conditions, smoothly giving the related annulation products
3oa (96% yield, >20:1 dr, 98% ee) and 3pa (98% yield, >20:1
dr, 96% ee). Moreover, the expansion of the ester- and amide-
substituted p-QMs (1q and 1r, respectively) to this
spiroannulation was also conducted, and the formation of
the desired carbonyl-functionalized products 3qa (56% yield,
>20:1 dr, 68% ee) and 3ra (85% yield, >20:1 dr, 67% ee) was
achieved, in which the decreased enantioselectivity might be
due in part to the negative influence of the electron-
withdrawing carbonyl group at its δ position on this Pd-
catalyzed enantioselective annulation. Notably, vinylogous p-
QM 1s was an excellent partner in this transformation, and the
structurally interesting product 3sa was provided in 70% yield
and excellent stereoselectivity (>20:1 dr, 98% ee). In addition,
α,α′-TMS-substituted p-QM 1t could smoothly react as well to
give the desired product 3ta in 73% yield with >20:1 dr and
99% ee.
activated by the complex resulting from Pd(dba)2 and chiral
phosphoramidite L8, rapidly generating Pd-TMM species A.
Due to the electron-withdrawing property of the cyano group,
A can readily isomerize to the thermodynamically stable
species B. As graphically simplified in TS-1, the chiral
phosphoramidite L8 backbone, which is three-dimensionally
distributed between the (S)-BINOL motif and the (2S,4R)-2-
C(OMe)Ph2-4-OTBS-pyrrolidinyl group, spatially renders the
si face of the nucleophilic ketenimine moiety accessible.
Because of the small steric effect of the linear ketenimine
group, the enantiotopic facial discrimination of the si face of p-
QM 1a is analogously controlled by minimizing the steric
hindrance resulting from interaction with the chiral phosphor-
amidite backbone. Accordingly, an asymmetric 1,6-addition of
p-QM 1a from the si face to the si face of the ketenimine
moiety proceeds via favorable transition state TS-1. Following
subsequent intramolecular dearomative cyclization through an
SN2′ process in TS-2, the formation of desired spirocyclic
C
https://dx.doi.org/10.1021/acs.orglett.0c01252
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
product 3aa is achieved with the regeneration of the palladium
catalyst for the next cycle.
Jing Zhang − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
In conclusion, a highly regio- and stereoselective asymmetric
catalytic (2+3) annulation of p-quinone methides with the
charge-delocalized C3 synthon (CN-TMM) has been
developed to forge a series of highly functionalized
spirocyclopentyl p-dienone building blocks. Significantly, a
novel type of non-C2-symmetric phosphoramidite ligand
consisting of an (S)-BINOL framework and L-hydroxypro-
line-derived amine units is designed and applied to the current
annulation, to some extent manifesting the impact of
phosphoramidites as chiral ligands in asymmetric catalysis.
This reaction not only provides a strategically complementary
enantioselective synthesis of functionalized chiral spirocyclo-
pentyl p-dienones but also enriches the chemistry of p-QMs in
the design of methodology for asymmetric catalytic (2+3)
annulation.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01252
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful for financial support from NSFC
(21825104 and 21801103), FRFCU (lzujbky-2018-12), and
PCSIRT (IRT_15R28).
REFERENCES
■
(1) (a) Coxon, D. T.; Price, K. R.; Howard, B.; Osman, S. F.; Kalan,
E. B.; Zacharius, R. M. Tetrahedron Lett. 1974, 15, 2921−2924.
(b) Edrada, R. A.; Stessman, C. C.; Crews, P. J. Nat. Prod. 2003, 66,
939−942. (c) Sorek, H.; Rudi, A.; Goldberg, I.; Aknin, M.; Kashman,
Y. J. Nat. Prod. 2009, 72, 784−786. (d) Díaz-Marrero, A. R.; Porras,
ASSOCIATED CONTENT
■
sı
* Supporting Information
́
G.; Aragon, Z.; de la Rosa, J. M.; Dorta, E.; Cueto, M.; D’Croz, L.;
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01252.
́
Mate, J.; Darias, J. J. Nat. Prod. 2011, 74, 292−295. (e) Park, H. B.;
Kim, Y.-J.; Lee, J. K.; Lee, K. R.; Kwon, H. C. Org. Lett. 2012, 14,
5002−5005. (f) Xu, K.; Jiang, J.-S.; Feng, Z.-M.; Yang, Y.-N.; Li, L.;
Zang, C.-X.; Zhang, P.-C. J. Nat. Prod. 2016, 79, 1567−1575.
(2) For selected examples, see: (a) Nicolaou, K. C.; Edmonds, D. J.;
Li, A.; Tria, G. S. Angew. Chem., Int. Ed. 2007, 46, 3942−3945.
(b) Nicolaou, K. C.; Li, A.; Ellery, S. P.; Edmonds, D. J. Angew. Chem.,
Int. Ed. 2009, 48, 6293−6295. (c) Nicolaou, K. C.; Li, A.; Edmonds,
D. J.; Tria, G. S.; Ellery, S. P. J. Am. Chem. Soc. 2009, 131, 16905−
16918.
(3) (a) Wu, Q.-F.; Liu, W.-B.; Zhuo, C.-X.; Rong, Z.-Q.; Ye, K.-Y.;
You, S.-L. Angew. Chem., Int. Ed. 2011, 50, 4455−4458. (b) Rousseaux,
S.; García-Fortanet, J.; Del Aguila Sanchez, M. A.; Buchwald, S. L. J.
Am. Chem. Soc. 2011, 133, 9282−9285. (c) Yoshida, M.; Nemoto, T.;
Zhao, Z.; Ishige, Y.; Hamada, Y. Tetrahedron: Asymmetry 2012, 23,
859−866.
Experimental procedures and spectral data (PDF)
Accession Codes
CCDC 1994600 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Authors
(4) (a) Yang, L.; Zheng, H.; Luo, L.; Nan, J.; Liu, J.; Wang, Y.; Luan,
X. J. Am. Chem. Soc. 2015, 137, 4876−4879. (b) Luo, L.; Zheng, H.;
Liu, J.; Wang, H.; Wang, Y.; Luan, X. Org. Lett. 2016, 18, 2082−2085.
(5) For only one report on asymmetric catalytic (2+3) annulation of
p-QMs, see: Ma, C.; Huang, Y.; Zhao, Y. ACS Catal. 2016, 6, 6408−
6412.
Chun-An Fan − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China; orcid.org/
0000-0003-4837-3394; Email: fanchunan@lzu.edu.cn
Xian-He Zhao − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China;
(6) Baeyer, A.; Villiger, V. Ber. Dtsch. Chem. Ges. 1903, 36, 2774−
2796.
(7) For very recent reviews on the chemistry of p-QMs, see:
(a) Parra, A.; Tortosa, M. ChemCatChem 2015, 7, 1524−1526.
(b) Caruana, L.; Fochi, M.; Bernardi, L. Molecules 2015, 20, 11733−
11764. (c) Chauhan, P.; Kaya, U.; Enders, D. Adv. Synth. Catal. 2017,
359, 888−912. (d) Lima, C. G. S.; Pauli, F. P.; Costa, D. C. S.; de
Souza, A. S.; Forezi, L. S. M.; Ferreira, V. F.; de Carvalho da Silva, F.
Eur. J. Org. Chem. 2020, 2020, 2650−2692.
(8) For the first report on 1,6-conjugate addition of p-QMs in
asymmetric catalysis, see: Chu, W.-D.; Zhang, L.-F.; Bao, X.; Zhao, X.-
H.; Zeng, C.; Du, J.-Y.; Zhang, G.-B.; Wang, F.-X.; Ma, X.-Y.; Fan, C.-
A. Angew. Chem., Int. Ed. 2013, 52, 9229−9233.
Email: zhaoxh@lzu.edu.cn
Authors
Zhi-Long Jia − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
Xian-Tao An − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
(9) For examples of asymmetric catalytic 1,6-conjugate addition of p-
QMs since 2017, see: (a) Zhang, X.-Z.; Gan, K.-J.; Liu, X.-X.; Deng,
Y.-H.; Wang, F.-X.; Yu, K.-Y.; Zhang, J.; Fan, C.-A. Org. Lett. 2017, 19,
3207−3210. (b) Li, S.; Liu, Y.; Huang, B.; Zhou, T.; Tao, H.; Xiao, Y.;
Liu, L.; Zhang, J. ACS Catal. 2017, 7, 2805−2809. (c) Kang, T.-C.;
Wu, L.-P.; Yu, Q.-W.; Wu, X.-Y. Chem. - Eur. J. 2017, 23, 6509−6513.
(d) Chen, M.; Sun, J. Angew. Chem., Int. Ed. 2017, 56, 4583−4587.
(e) Chen, M.; Sun, J. Angew. Chem., Int. Ed. 2017, 56, 11966−11970.
(f) Wang, H.; Wang, K.; Man, Y.; Gao, X.; Yang, L.; Ren, Y.; Li, N.;
Tang, B.; Zhao, G. Adv. Synth. Catal. 2017, 359, 3934−3939. (g) Gao,
Y.-Y.; Hua, Y.-Z.; Wang, M.-C. Adv. Synth. Catal. 2018, 360, 80−85.
Yu-Hua Deng − Key Laboratory of Medicinal Chemistry for
Natural Resource, Ministry of Education, School of Chemical
Science and Technology, Yunnan University, Kunming 650091,
China; orcid.org/0000-0002-1983-8490
Hui-Bin Wang − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
Kang-Ji Gan − State Key Laboratory of Applied Organic
Chemistry, College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
D
https://dx.doi.org/10.1021/acs.orglett.0c01252
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(h) Santra, S.; Porey, A.; Jana, B.; Guin, J. Chem. Sci. 2018, 9, 6446−
6450. (i) Li, W.; Xu, X.; Liu, Y.; Gao, H.; Cheng, Y.; Li, P. Org. Lett.
2018, 20, 1142−1145. (j) Rahman, A.; Zhou, Q.; Lin, X. Org. Biomol.
Chem. 2018, 16, 5301−5309. (k) Sun, Z.; Sun, B.; Kumagai, N.;
Shibasaki, M. Org. Lett. 2018, 20, 3070−3073. (l) Zhang, L.; Yuan,
H.; Lin, W.; Cheng, Y.; Li, P.; Li, W. Org. Lett. 2018, 20, 4970−4974.
(m) Fan, Y.-J.; Zhou, L.; Li, S. Org. Chem. Front. 2018, 5, 1820−1824.
(n) Wang, J.-R.; Jiang, X.-L.; Hang, Q.-Q.; Zhang, S.; Mei, G.-J.; Shi,
F. J. Org. Chem. 2019, 84, 7829−7839. (o) Wang, K.; Xiang, Y.; Shi,
Z.; Wang, H.; Li, N.; Tang, B. Org. Biomol. Chem. 2019, 17, 6351−
Bernardinelli, G.; Alexakis, A. Inorg. Chim. Acta 2006, 359, 1826−
1836.
́
6354. (p) Toran, R.; Vila, C.; Sanz-Marco, A.; Munoz, M. C.; Pedro,
̃
J. R.; Blay, G. Eur. J. Org. Chem. 2020, 2020, 627−630. (q) Qi, S.-S.;
Jiang, Z.-H.; Chu, M.-M.; Wang, Y.-F.; Chen, X.-Y.; Ju, W.-Z.; Xu, D.-
Q. Org. Biomol. Chem. 2020, 18, 2398−2404. (r) Zhou, J.; Bai, L.-J.;
Liang, G.-J.; Xu, Q.-G.; Zhou, L.-P.; Zhou, H. Org. Biomol. Chem.
2020, 18, 2641−2645.
(10) For catalytic asymmetric (4+2) annulations of p-QMs, see:
(a) Zhao, K.; Zhi, Y.; Shu, T.; Valkonen, A.; Rissanen, K.; Enders, D.
Angew. Chem., Int. Ed. 2016, 55, 12104−12108. (b) Zhang, L.; Liu, Y.;
Liu, K.; Liu, Z.; He, N.; Li, W. Org. Biomol. Chem. 2017, 15, 8743−
8747. (c) Zhang, L.; Zhou, X.; Li, P.; Liu, Z.; Liu, Y.; Sun, Y.; Li, W.
RSC Adv. 2017, 7, 39216−39220. (d) Zhang, Z.-P.; Xie, K.-X.; Yang,
C.; Li, M.; Li, X. J. Org. Chem. 2018, 83, 364−373. (e) Jiang, X.-L.;
Wu, S.-F.; Wang, J.-R.; Mei, G.-J.; Shi, F. Adv. Synth. Catal. 2018, 360,
4225−4235. (f) Zhang, Z.-P.; Chen, L.; Li, X.; Cheng, J.-P. J. Org.
Chem. 2018, 83, 2714−2724. (g) Duan, C.; Ye, L.; Xu, W.; Li, X.;
Chen, F.; Zhao, Z.; Li, X. Chin. Chem. Lett. 2018, 29, 1273−1276.
(h) Yang, G.-H.; Zhao, Q.; Zhang, Z.-P.; Zheng, H.-L.; Chen, L.; Li,
X. J. Org. Chem. 2019, 84, 7883−7893. (i) Zhao, M.-X.; Xiang, J.;
Zhao, Z.-Q.; Zhao, X.-L.; Shi, M. Org. Biomol. Chem. 2020, 18, 1637−
1646.
(11) For a previous investigation of the synthesis of spirocyclopentyl
p-dienones, see: Zhang, X.-Z.; Deng, Y.-H.; Gan, K.-J.; Yan, X.; Yu, K.-
Y.; Wang, F.-X.; Fan, C.-A. Org. Lett. 2017, 19, 1752−1755.
(12) For the first example of TMMs in organic synthesis, see: Trost,
B. M.; Chan, D. M. T. J. Am. Chem. Soc. 1979, 101, 6429−6432.
(13) For reviews of the chemistry of TMMs, see: (a) Trost, B. M.
Angew. Chem., Int. Ed. Engl. 1986, 25, 1−114. (b) Trost, B. M. Pure
Appl. Chem. 1988, 60, 1615−1626. (c) Allen, B. D. W.; Lakeland, C.
P.; Harrity, J. P. A. Chem. - Eur. J. 2017, 23, 13830−13857.
(14) For selected catalytic symmetric (3+2) annulations of TMMs
with olefins, see: (a) Yamamoto, A.; Ito, Y.; Hayashi, T. Tetrahedron
Lett. 1989, 30, 375−378. (b) Trost, B. M.; Stambuli, J. P.; Silverman,
̈
S. M.; Schworer, U. J. Am. Chem. Soc. 2006, 128, 13328−13329.
(c) Trost, B. M.; Zhang, L.; Lam, T. M. Org. Lett. 2018, 20, 3938−
3942. (d) Trost, B. M.; Wang, Y. Angew. Chem., Int. Ed. 2018, 57,
11025−11029. (e) Trost, B. M.; Zell, D.; Hohn, C.; Mata, G.;
Maruniak, A. Angew. Chem., Int. Ed. 2018, 57, 12916−12920.
(f) Trost, B. M.; Jiao, Z.; Hung, C.-I. Angew. Chem., Int. Ed. 2019,
58, 15154−15158. (g) Trost, B. M.; Shinde, A. H.; Wang, Y.; Zuo, Z.;
Min, C. ACS Catal. 2020, 10, 1969−1975.
(15) For selected catalytic symmetric (3+2) annulations of TMMs
with carbonyl compounds, see: (a) Trost, B. M.; Bringley, D. A.;
Silverman, S. M. J. Am. Chem. Soc. 2011, 133, 7664−7667. (b) Trost,
B. M.; Mata, G. Angew. Chem., Int. Ed. 2018, 57, 12333−12337.
(16) For selected catalytic symmetric (3+2) annulations of TMMs
with imines, see: (a) Trost, B. M.; Silverman, S. M. J. Am. Chem. Soc.
2012, 134, 4941−4954. (b) Trost, B. M.; Lam, T. M.; Herbage, M. A.
J. Am. Chem. Soc. 2013, 135, 2459−2461.
(17) Trost, B. M.; Nanninga, T. N.; Satoh, T. J. Am. Chem. Soc.
1985, 107, 721−723.
(18) No reaction was observed when the CN group of 2a was
replaced with H, Ph, or a vinyl group.
(19) For the screening of solvents, see the Supporting Information.
(20) CCDC 1994600 contains the supplementary X-ray crystallo-
graphic data of 3da (for details, see the Supporting Information).
(21) (a) Shi, W.-J.; Xie, J.-H.; Zhou, Q.-L. Tetrahedron: Asymmetry
2005, 16, 705−710. (b) Filipuzzi, S.; Pregosin, P. S.; Albinati, A.;
Rizzato, S. Organometallics 2006, 25, 5955−5964. (c) Mikhel, I. S.;
E
https://dx.doi.org/10.1021/acs.orglett.0c01252
Org. Lett. XXXX, XXX, XXX−XXX