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Enantioselective Trapping of Pd-Containing 1,5-Dipoles by Photo-generated Ketenes: Access to 7-Membered Lactones Bearing Chiral Quaternary Stereocenters Wen-Jing Xiao, Yi Wei, Song Liu, Miao-Miao Li, Yi Li, Yu Lan, and Liang-Qiu Lu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b12095 • Publication Date (Web): 12 Dec 2018 Downloaded from http://pubs.acs.org on December 12, 2018
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Journal of the American Chemical Society
Enantioselective Trapping of Pd-Containing 1,5-Dipoles by Photo-generated Ketenes: Access to 7-Membered Lactones Bearing Chiral Quaternary Stereocenters Yi Wei,† Song Liu,‡ Miao-Miao Li,† Yi Li,† Yu Lan,‡ Liang-Qiu Lu,†,* and Wen-Jing Xiao†,¶,* †CCNU-uOttawa
Joint Research Centre, Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, China ‡School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China ¶State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China Supporting Information Placeholder ABSTRACT: An enantioselective [5+2] cycloaddition of vinylethylene carbonates and α-diazoketones was achieved for the first time by merging photoactivation and asymmetric Pd catalysis. The key to the success of this method is the enantioselective trapping of Pd-containing, 1,5-dipolar intermediates by ketenes, a class of reactive C2 synthons, which were generated in an in situ and traceless manner under visible light irradiation. Through this trapping, a variety of 7-membered lactones bearing challenging chiral quaternary stereocenters can be accessed in a facile manner with good efficiency and high enantioselectivity (up to 99% yield and 96:4 er).
It has been well known that the construction of medium-sized rings in an efficient and selective way is an important and challenging task in organic synthesis.1 Among the ongoing efforts towards this goal, [5+2] cycloadditions using reactive 1,5-dipolar synthons is a promising approach to 7-membered rings possibly due to the ready availability of the precursors (Figure 1a).2 In particular, elegant [5+2] cycloadditions via the in situ formation of transition metal (TM)-containing 1,5-dipolar intermediates though TM catalysis have been established.3-5 During these investigations, asymmetric variants have been successfully achieved;4,5 however, the successful methods have been largely limited to intramolecular Ru- or Rh-catalyzed processes using chiral feedstocks.4 To make TM-catalyzed dipolar cycloadditions more powerful and general in the synthesis of medium-sized rings, new strategies for achieving these transformation in high efficiency and selectivity and under mild reaction conditions are required. Ketenes are reactive and versatile C2 synthons that are widely used in asymmetric [n+2] cycloadditions (n = 2~4) usually through organocatalysis or Lewis acid catalysis.6-9 However, the use of ketenes to access medium-sized rings is still underdeveloped. Last year, we established a strategy that effectively combined photoactivation and asymmetric Pd catalysis for the synthesis of chiral quinolinones.10d We found that the sequential visible light-induced Wolff rearrangement and Pdcatalyzed asymmetric [4+2] cycloaddition of a generated ketene species with a vinyl benzoxazinone could be efficiently carried out under extremely mild conditions. In this work, inspired by the attractive features described above, we devised a Pd-catalyzed [5+2] dipolar cycloaddition by using photogenerated ketenes11
and vinylethylene carbonates (VECs)12,13 for the synthesis of chiral 7-membered lactones14 bearing a chiral quaternary stereocenter. a) Illustration of [5+2] cycloadditions Y
X
[5+2]
+
cycloaddition
X 1,5-dipolar synthon dipolarophile
• synthetic efficiency • chemoselectivity
Y
• stereoselectivity
7-membered ring
1
O 1
1
Ar
5
O
NTs
Ar'
5
Ru MLn
Co
N
1 5
Rh
X 5 X = C, NTs, O
Ir
Features: in-situ formation, catalytic amount of TM, catalyst-controlled selectivity Problem: limited success on the asymmetric intermolecular [5+2] cycloaddtions b) This work: the combination of photoactivation and palladium catalysis for the asymmetric [5+2] cycloadditions O O R2 O O 3 R3 R Pd + O O R2 R1 N2 • room temperature 1 2 R1 3 • visible light irradiation Wolff • seven-membered ring rearrangement • chiral quaternary carbon
[Pd(0)] CO2 R1 + O A
[Pd(II)]
R2
• R
3
4
O
nucleophilic addition of O-anion
R2 R3 O
AAA process 1 R b a O [Pd(II)] B
Figure 1. Reaction design: enantioselective synthesis of 7membered lactones via a visible light-induced, Pd-catalyzed asymmetric [5+2] cycloaddition. As simply depicted in Figure 1b, the initial reaction between VECs 1 and a Pd(0) catalyst would generate Pd-containing π–allyl dipolar intermediate A; irradiation of α-diazoketones 2 with visible light would tracelessly release ketene species (4) via a Wolff rearrangement.11 Then, we proposed that the nucleophilic addition of the oxygen anion of intermediate A to ketenes 4 would smoothly form new zwitterionic intermediate B. Finally, an intramolecular asymmetric allylic alkylation (AAA) of the enolate fragment and the π–allyl-Pd fragment would furnish the desired 7membered lactones. Although feasible in principle, there are several challenges inherent in the planned pathway. The first is the regioselectivity in the last ring-closing step, in which the terminal attack to form the desired 7-membered ring (path a) and the inner attack to form the undesired 5-membered ring (path b)
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are competitive. However, the important breakthrough by Zhao, who recently developed [5+4] cycloadditions using VECs and azadienes,13a implied the feasibility of using intermediates A as a 1,5-dipolar synthon. The second issue is the enantio-control in the formation of the chiral quaternary stereocenter, which is challenging despite the fact that such centers are important and widespread in biologically significant molecules.15 The final important challenge is the matching of the generation of intermediates A and ketenes 4 and their subsequent cycloadditions; otherwise, both of these reactive species, as well as αdiazoketones, are prone to decomposition in the presence of a Pd catalyst.12,13,16 In our experience, these processes can be controlled by using suitable ligands and light sources.17 Table 1. Optimization of the Reaction Conditionsa O O
O
O +
O
Me
Ph
Ph
Pd
N2
1a
Me
O
Ph
2a
Ph
3aa
entry
ligand
solvent
yield (%)b
erc
1
L1
DCM
44
85:15
2
L2
DCM
0
-
3
L3
DCM
0
-
4
L4
DCM
0
-
5
L5
DCM
13
82:18
6
L6
DCM
59
86:14
7
L7
DCM
69
and chiral hybrid ligands L3 and L4 failed to afford the desired product. Then, we turned our attention to chiral monodentate ligands. Based on previous works on VEC reagents12,13 and our works on TM-catalyzed dipolar cycloadditions,10 we extensively investigated various phosphoramidite ligands (L5-L9).18 An obvious improvement in the enantioselectivity was observed when using chiral ligand L9. Other phosphoramidite ligands (L5-L8) gave inferior results compared with L9. Encouraged by this promising result, the solvent effect was systematically investigated using L9 as the ligand (Table 1, entries 9-12), and the reaction yield was further increased to 70% with good enantiocontrol (95:5 er) when a THF/CHCl3 mixture was used as the solvent (Table 1, entry 12). Changing the ratio of Pd/L provided a higher yield and similar enantioselectivity (Table 1, entry 13). A satisfactory result can still be achieved when the loading of the Pd catalyst is reduced (Table 1, entry 14, 99% yield and 96:4 er). Having established the optimal conditions, we started to explore the generality of this catalytic asymmetric [5+2] cycloaddition. As summarized in Table 2, a wide range of VECs with electronically varied substituents, such as Me, F, Cl, Br and CF3, at the 4 position of the phenyl ring could readily participate in the [5+2] cycloaddition, affording the corresponding cycloadducts in good yields and with high enantioselectivities (Table 2, entries 1-6, 3aa-3fa: 91-99% yields and 93:7-96:4 er). Furthermore, substrates with substituents at different positions, for example, 3-Br- or 2-Me-substituted phenyl groups, and a 3,4benzodioxolaneTable 2. Scope of the VEC Partnersa O
70:30
8
L8
DCM
44
75:25
9
L9
DCM
54
96:4
10
L9
THF
80
90:10
11
L9
CHCl3
60
96:4
12d
L9
THF/CHCl3
70
95:5
13d,e
L9
THF/CHCl3
90
96:4
14d-f
L9
THF/CHCl3
99
96:4
O
O
O
O NH
Ph
HN
PPh2 PPh2
O
PPh2 Ph2P
O
L1
(PhO)2P N t-Bu
L2
S Ar Bn Ar = 4-Br-C6H4
L3
L4
Me O P O
Et N Et L5
Ph N Ph Me L6
N
Me N Ph
Me L7
L8
Me N Ph Ph L9
To verify the above proposal, an assay of potential chiral ligands was first conducted for the [5+2] cycloaddition reaction of phenyl-substituted VEC 1a and α-diazoketone 2a using Pd2(dba)3·CHCl3 as a precatalyst. As shown in Table 1, we found that Trost’s ligand (L1) indeed promoted the reaction with good enantioselectivity but in a low yield. Chiral diphosphine ligand L2
Ph N2
Me
O
Pd standard conditions
2a
R1
Ph
3
R2
entry
1: R1, R2
3
yield (%)b
erc
1
1a: Ph, H
3aa
99 (90)d
96:4
2
1b: 4-Me-C6H4, H
3ba
98
95:5
3
1c: 4-F-C6H4, H
3ca
99
95:5
4
1d: 4-Cl-C6H4, H
3da
91
95:5
5
1e: 4-Br-C6H4, H
3ea
92
95:5
6
1f: 4-CF3-C6H4, H
3fa
93
93:7
7
1g: 3-Br-C6H4, H
3ga
99
95:5
8
1h: 2-Me-C6H4, H
3ha
99
96:4
3ia
99
96:4
9
Ph
O PPh2 N
+
O
Me
1 R2
Conditions: 1a (0.1 mmol), 2a (0.2 mmol), Pd2(dba)3•CHCl3 (5 mol%), chiral ligand (11 mol%) in anhydrous DCM (2 mL) at rt under irradiation of 6 W blue LEDs (light intensity = 32.8 mw/cm2). bNMR yield using 1,3,5-trimethoxybenzene as an internal standard. cDetermined by chiral HPLC analysis. dMixed solvent (1:3), 3 mL. eUsing 22 mol% of ligand. fUsing 2.5 mol% of Pd (dba) •CHCl and 11 2 3 3 mol% of ligand. dba: dibenzylideneacetone; rt: room temperature.
O
O R1
a
O
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O
1i:
O
,H
10
1j: β-naphthyl, H
3ja
99
94:6
11
1k: 3-thienyl, H
3ka
92
84:16
12e
1l: cyclohexyl, H
3la
42
73:27
13
1m: Ph, Ph
3ma
42
74:26
Standard conditions as indicated in entry 14 in Table 1. bIsolated yields. cDetermined by chiral HPLC analysis. dA gram-scale reaction in a flow photoreactor. eL7 was used. a
fused system, were compatible with this cycloaddition. The desired cycloadducts were prepared with satisfactory reaction efficiencies and stereoselectivities (Table 2, entries 7-9, 3ga-3ia: 99% yields and 95:5-96:4 er). VECs bearing naphthyl and heteroaryl moieties were also suitable for this transformation and were converted to products 3ja (Table 2, entry 10: 99% yield and
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Journal of the American Chemical Society 94:6 er) and 3ka (Table 2, entry 11: 92% yield and 84:16 er). The asymmetric [5+2] cycloaddition could be extended to alkylsubstituted VECs. For example, substrate 1l, bearing a cyclohexyl group, could be converted to lactone 3la, albeit in a moderate yield and ee with the established conditions (Table 2, entry 12). Besides, substrate 1m having a phenyl group at alkenyl motif, could also be converted to the desired product 3ma in a moderate yield and enantioselectivity (Table 2, entry 13). Subsequently, the substrate scope with respect to αdiazoketone 2 was investigated. As summarized in Table 3, the introduction of various substituents at the para or meta positions of the phenyl ring of the α-diazoketone was well tolerated in this reaction, and corresponding products 3ab-3ag were obtained in good yields with high enantioselectivities (88-99% yields and 95:5-96:4 er). Moreover, β-naphthyl-substituted α-diazoketone 2h could be converted to corresponding 7-membered lactone 3ah in good yield and excellent enantioselectivity (99% yields and 95:5 er). The influence of alkyl substituents on the α-diazoketones on the reaction outcome was also examined. Ethyl, n-butyl, i-propyl, and benzyl substituents are all well tolerated, leading to chiral
To elucidate the reaction mechanism, we first performed a set of experiments using chiral ligand L9 with various optical purities. As depicted in Figure 2a, regardless of the ratio of the Pd(0) source to the ligand L9 (Pd/L = 1 or 2), nearly the same positive nonlinear effect was observed between the ee value of the ligand and that of the cycloadduct. This result indicated that the effective catalyst in this catalytic asymmetric [5+2] cycloaddition is the organometallic complex Pd(L9)2. Furthermore, characteristic mass signals of two key Pd intermediates (A’ and B’) involving Pd(L9)2 were detected by analyzing the reaction system containing VEC 1a and α-diazoketone 2a under standard conditions (Figure 2b). Based on this information together with the absolute configuration of cycloadduct 3ia (Figure 2c)19 and the optimized structures of alkoxy-Pd intermediates through DFT calculation,20 we proposed two possible models to explain the stereochemical outcome. As illustrated in Figure 2d, the steric match among the π-allyl fragment, the ketene and the chiral ligand might be very a)
c)
Table 3. Scope of the α-Diazoketone Partnersa O O
+
O
Ar
R'
Ph
N2
1a
entry
O
O
O
Pd standard conditions
2
2: Ar, R’
Ph
R'
standard 1a conditions + 2a L9 with varied optical purity
Ar
3
3
yield(%)
er
b
3aa
product 3ia (CCDC 1856495)
c
1
2b: 4-Me-C6H4, Me
3ab
99
95:5
2
2c: 4-Cl-C6H4, Me
3ac
98
96:4
3
2d: 4-Br-C6H4, Me
3ad
88
96:4
4
2e: 3-MeO-C6H4, Me
3ae
91
96:4
5
2f: 3-F-C6H4, Me
3af
97
96:4
6
2g: 3-Cl-C6H4, Me
3ag
98
96:4
7
2h: β-naphthyl, Me
3ah
99
95:5
8
2i: Ph, Et
3ai
96
94:6
9
2j: Ph, n-Bu
3aj
94
95:5
10
2k: Ph, i-Pr
3ak
59
77:23
3al
97
96:4
b)
intermediate A': [M+H]+
intermediate B': [M+H]+
O N2
11
Bn
2l: 12
2m: Ph,
3am
98
95:5
13
2n: Ph,
3an
82
93:7
14 15
2o: Ph, 2p: Ph,
3ao
BnO
98
95:5
d) Me
N
O O
TBSO
3ap
59
95:5
3aq
83
88:12
Pd
N2
2q:
O O
Ph
N
N O P
O
O
16
4a
P Ph
A'
Si-face favored P Me
O O
N
Pd
Ph
O
O
P O
O
Ph
B'
a
Figure 2. Preliminary mechanistic investigations. (a) Nonlinear experiments. (b) ESI-MS analysis of the Pd complexes. (c) The X-ray crystal structure of product 3ia. (d) Proposed stereoinduction modes.
lactones 3ai-3al in good yields with excellent enantioselectivities. Gratifyingly, α-diazoketones bearing functional groups such as allyl, alkynyl, and ether groups could also readily participate in this reaction (59-98% yields and 93:7-95:5 er). Additionally, cyclic α-diazoketone 2q smoothly underwent the developed reaction, and chiral lactone 3aq bearing a spiro-quaternary carbon was delivered in 83% yield with 88:12 er.
important for achieving the high level of enantiocontrol. The phenyl groups on the amino in ligand L9 might contribute to the obvious improvement in the enantioselectivity compared with other phosphoramidite ligands L5-L8, although further studies on the stereoselectivity are still required. In conclusion, we have successfully achieved the first visible light-induced, Pd-catalyzed asymmetric [5+2] cycloaddition of VECs with α-diazoketones. This methodology provides an
Standard conditions as indicated in entry 14 in Table 1. bIsolated yields. cDetermined by chiral HPLC analysis.
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enantioselective approach for accessing a variety of 7-membered lactones bearing chiral quaternary stereocenters. Preliminary mechanistic studies suggested that the binding of two phosphoramidite ligands to the palladium center was responsible for the high reaction efficiency and enantioselectivity. Although an in-deep investigation of the origin of the chemo- and enantioselectivity is still necessary, the transformation described in this work represents a significant expansion of ketene chemistry into the construction of challenging medium-sized rings.
ASSOCIATED CONTENT Supporting Information Experimental procedures, and characterization data for all the products. The Supporting Information is available free of charge on the ACS Publications website.
AUTHOR INFORMATION Corresponding Author
[email protected];
[email protected] Notes The authors declare no competing financial interests.
ACKNOWLEDGMENT We are grateful to the National Science Foundation of China (No. 21822103, 21820102003, 21772052, 21772053, 21572074 and 21472057), the Program of Introducing Talents of Discipline to Universities of China (111 Program, B17019) and the Natural Science Foundation of Hubei Province (2017AHB047) for support of this research.
REFERENCES (1) (a) Molander, G. A. Diverse Methods for Medium Ring Synthesis. Acc. Chem. Res. 1998, 31, 603-609. (b) Mehta, G.; Singh, V. Progress in the Construction of Cyclooctanoid Systems: New Approaches and Applications to Natural Product Syntheses. Chem. Rev. 1999, 99, 881-930. (c) Yet, L. Metal-Mediated Synthesis of Medium-Sized Rings. Chem. Rev. 2000, 100, 2963-3008. (2) (a) Ylijoki, K. E. O.; Stryker, J. M. [5+2] Cycloaddition Reactions in Organic and Natural Product Synthesis. Chem. Rev. 2013, 113, 2244-2266. (b) Pellissier, H. Recent Developments in the [5+2] Cycloaddition. Adv. Synth. Catal. 2018, 360, 1551-1583. The 1η- or 3η-metal complexes have not been satisfactorily described in the literature, and here we chose the latter form. (3) For pioneering work: (a) Wender, P. A.; Takahashi, H.; Witulski, B. Transition Metal Catalyzed [5+2] Cycloadditions of Vinylcyclopropanes and Alkynes: A Homolog of the Diels-Alder Reaction for the Synthesis of Seven-Membered Rings. J. Am. Chem. Soc. 1995, 117, 4720-4721. (b) Wender, P. A.; Rieck, H.; Fuji, M. The Transition Metal-Catalyzed Intermolecular [5+2] Cycloaddition: The Homologous Diels-Alder Reaction. J. Am. Chem. Soc. 1998, 120, 10976-10977. For recent selected examples: (c) Yu, Z.-X.; Cheong, P. H.-Y.; Liu, P.; Legault, C. Y.; Wender, P. A.; Houk, K. N. Origins of Differences in Reactivities of Alkenes, Alkynes, and Allenes in [Rh(CO)2Cl]2-Catalyzed (5+2) Cycloaddition Reactions with Vinylcyclopropanes. J. Am. Chem. Soc. 2008, 130, 23782379. (d) Jiao, L.; Yu, Z.-X. Vinylcyclopropane Derivatives in TransitionMetal-Catalyzed Cycloadditions for the Synthesis of Carbocyclic Compounds. J. Org. Chem. 2013, 78, 6842-6848. (4) For selected examples using chiral substrates, see: (a) Wender, P. A.; Fuji, M.; Husfeld, C. O.; Love, J. A. Rhodium-Catalyzed [5+2] Cycloadditions of Allenes and Vinylcyclopropanes: Asymmetric Total Synthesis of (+)-Dictamnol. Org. Lett. 1999, 1, 137-140. (b) Wender, P. A.; Bi, F. C.; Brodney, M. A.; Gosselin, F. Asymmetric Synthesis of the Tricyclic Core of NGF-Inducing Cyathane Diterpenes via a Transition-
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Metal-Catalyzed [5+2] Cycloaddition. Org. Lett. 2001, 3, 2105-2108. (c) Trost, B. M.; Hu, Y.; Horne, D. B. Total Synthesis of (+)-Frondosin A. Application of the Ru-Catalyzed [5+2] Cycloaddition. J. Am. Chem. Soc. 2007, 129, 11781-11790. (d) Feng, J.-J.; Lin, T.-Y.; Wu, H.-H.; Zhang, J. Transfer of Chirality in the Rhodium-Catalyzed Intramolecular Formal Hetero-[5+2] Cycloaddition of Vinyl Aziridines and Alkynes: Stereoselective Synthesis of Fused Azepine Derivatives. J. Am. Chem. Soc. 2015, 137, 3787-3790. (e) Feng, J.-J.; Lin, T.-Y.; Wu, H.-H.; Zhang, J. Modular Access to the Stereoisomers of Fused Bicyclic Azepines: Rhodium-Catalyzed Intramolecular Stereospecific Hetero-[5+2] Cycloaddition of Vinyl Aziridines and Alkenes. Angew. Chem. Int. Ed. 2015, 54, 15854-15858. (f) Feng, J.-J.; Lin, T.-Y.; Zhu, C.-Z.; Wang, H.; Wu, H.-H.; Zhang, J. The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(I)-Catalyzed Intermolecular Cycloadditions of Vinyl Aziridines and Alkynes. J. Am. Chem. Soc. 2016, 138, 2178-2181. (g) Zhu, L.; Qi, X.; Lan, Y. Rhodium-Catalyzed Hetero-(5+2) Cycloaddition of Vinylaziridines and Alkynes: A Theoretical View of the Mechanism and Chirality Transfer. Organometallics 2016, 35, 771-777. (5) Two isolated examples using chiral Rh catalysts: (a) Wender, P. A.; Haustedt, L. O.; Lim, J.; Love, J. A.; Williams, T. J.; Yoon, J.-Y. Asymmetric Catalysis of the [5+2] Cycloaddition Reaction of Vinylcyclopropanes and π-Systems. J. Am. Chem. Soc. 2006, 128, 63026303. (b) Shintani, R.; Nakatsu, H.; Takatsu, K.; Hayashi, T. RhodiumCatalyzed Asymmetric [5+2] Cycloaddition of Alkyne-Vinylcyclopropanes. Chem. Eur. J. 2009, 15, 8692-8694. (6) For two selected reviews: (a) Paull, D. H.; Weatherwax, A.; Lectka, T. Catalytic, Asymmetric Reactions of Ketenes and Ketene Enolates. Tetrahedron 2009, 65, 6771-6803. (b) Allen, A. D.; Tidwell, T. T. Ketenes and Other Cumulenes as Reactive Intermediates. Chem. Rev. 2013, 113, 7287-7342. (7) Two Pioneering work on asymmetric [2+2] cycloadditions: (a) Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Drury, W. J.; Lectka, T. Catalytic, Asymmetric Synthesis of β-Lactams. J. Am. Chem. Soc. 2000, 122, 78317832. (b) Taggi, A. E.; Hafez, A. M.; Wack, H.; Young, B.; Ferraris, D.; Lectka, T. The Development of the First Catalyzed Reaction of Ketenes and Imines: Catalytic, Asymmetric Synthesis of β-Lactams. J. Am. Chem. Soc. 2002, 124, 6626-6635. (8) Selected work on asymmetric [3+2] cycloadditions: (a) Duguet, N.; Slawin, A. M. Z.; Smith, A. D. An Asymmetric Hetero-Claisen Approach to 3-Alkyl-3-aryloxindoles. Org. Lett. 2009, 11, 3858-3861. (b) Shao, P. L.; Chen, X. Y.; Ye, S. Formal [3+2] Cycloaddition of Ketenes and Oxaziridines Catalyzed by Chiral Lewis Bases: Enantioselective Synthesis of Oxazolin-4-ones. Angew. Chem. Int. Ed. 2010, 49, 8412-8416. (9) Selected work on asymmetric [4+2] cycloadditions: (a) Bekele, T.; Shah, M. H.; Wolfer, J.; Abraham, C. J. Weatherwax, A. Lectka, T. Catalytic, Enantioselective [4+2]-Cycloadditions of Ketene Enolates and o-Quinones: Efficient Entry to Chiral, α-Oxygenated Carboxylic Acid Derivatives. J. Am. Chem. Soc. 2006, 128, 1810-1811. (b) Xu, X.; Wang, K.; Nelson, S. G. Catalytic Asymmetric [4+2] Cycloadditions of Ketenes and N-Thioacyl Imines: Alternatives for Direct Mannich Reactions of Enolizable Imines. J. Am. Chem. Soc. 2007, 129, 11690-11691. (c) Huang, X.-L.; He, L.; Shao, P.-L.; Ye, S. [4+2] Cycloaddition of Ketenes with NBenzoyldiazenes Catalyzed by N-Heterocyclic Carbenes. Angew. Chem. Int. Ed. 2009, 48, 192-195. (d) Hao, X.-Y.; Liu, X.-H.; Li, W.; Tan, F.; Chu, Y.-Y.; Zhao, X.-H.; Lin, L.-L.; Feng, X.-M. Chiral Lewis Acid Catalyzed Asymmetric Cycloadditions of Disubstituted Ketenes for the Synthesis of β-Lactones and δ-Lactones. Org. Lett. 2014, 16, 134-137. (10) For a related review, see: (a) Lu, L.-Q.; Li, T.-R.; Wang, Q.; Xiao, W.-J. Beyond Sulfide-centric Catalysis: Recent Advances in the Catalytic Cyclization Reactions of Sulfur Ylides. Chem. Soc. Rev. 2017, 46, 41354149. For selected work, see: (b) Wei, Y.; Lu, L.-Q.; Li, T.-R.; Feng, B.; Wang, Q.; Xiao, W.-J.; Alper, H. P,S Ligands for the Asymmetric Construction of Quaternary Stereocenters in Palladium-Catalyzed Decarboxylative [4+2] Cycloadditions. Angew. Chem. Int. Ed. 2016, 55, 2200-2204. (c) Wang, Q.; Li, T.-R.; Lu, L.-Q.; Li, M.-M.; Zhang, K.; Xiao, W.-J. Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper-Allenylidene Intermediates. J. Am. Chem. Soc. 2016, 138, 83608363. (d) Li, M.-M.; Wei, Y.; Liu, J.; Chen, H-W.; Lu, L.-Q.; Xiao, W.-J. Sequential Visible-Light Photoactivation and Palladium Catalysis
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Journal of the American Chemical Society Enabling Enantioselective [4+2] Cycloadditions. J. Am. Chem. Soc. 2017, 139, 14707-14713. (11) For a review: (a) Kirmse, W. 100 Years of the Wolff
Rearrangement. Eur. J. Org. Chem. 2002, 2002, 2193-2256. For recent work on photo-Wolff rearrangement, see: (b) Burdzinski, G. T.; Wang, J.; Gustafson, T. L.; Platz, M. S. Study of Concerted and Sequential Photochemical Wolff Rearrangement by Femtosecond UV-vis and IR Spectroscopy. J. Am. Chem. Soc. 2008, 130, 37463747. (c) Wang, J.; Burdzinski, G.; Kubicki, J.; Platz, M. S. Ultrafast UV-Vis and IR Studies of p-Biphenylyl Acetyl and Carbomethoxy Carbenes. J. Am. Chem. Soc. 2008, 130, 11195-11209. (d) Vaske, Y. S. M.; Mahoney, M. E.; Konopelski, J. P.; Rogow, D. L.; McDonald, W. J. Enantiomerically Pure trans-β-Lactams from α-Amino Acids via Compact Fluorescent Light (CFL) Continuous-Flow Photolysis. J. Am. Chem. Soc. 2010, 132, 11379-11385. (e) Bernardim, B.; Hardman-Baldwinb, A. M.; Burtoloso, A. C. B. LED Lighting as A Simple, Inexpensive, and Sustainable Alternative for Wolff Rearrangements. RSC Adv. 2015, 5, 13311-13314.
(18) (a) Teichert, J. F.; Feringa, B. L. Phosphoramidites: Privileged Ligands in Asymmetric Catalysis. Angew. Chem. Int. Ed. 2010, 49, 24862528. (b) Zhou, C.-Y.; Zheng, C.; You, S.-L. Transition-Metal-Catalyzed Asymmetric Allylic Dearomatization Reactions. Acc. Chem. Res. 2014, 47, 2558-2573. (19) The absolute configuration of 3ia was established by the X-ray diffraction analysis (CCDC 1856495). (20) Please see the details on the DFT calculation in the Supporting Information.
(12) (a) Khan, A.; Zheng, R.; Kan, Y.; Ye, J.; Xing, J.; Zhang, Y. J. Palladium-Catalyzed Decarboxylative Cycloaddition of Vinylethylene Carbonates with Formaldehyde: Enantioselective Construction of Tertiary Vinylglycols. Angew. Chem. Int. Ed. 2014, 53, 6439-6442. (b) Khan, A.; Yang, L.; Xu, J.; Jin, L. Y.; Zhang, Y. J. Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Michael Acceptors: Construction of Vicinal Quaternary Stereocenters. Angew. Chem. Int. Ed. 2014, 53, 11257-11260. (13) Selected application of VECs in cycloadditions: (a) Yang, L.-C.; Rong, Z.-Q.; Wang, Y.-N.; Tan, Z. Y.; Wang, M.; Zhao, Y. Construction of NineMembered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition. Angew. Chem. Int. Ed. 2017, 56, 2927-2931. (b) Rong, Z.Q.; Yang, L.-C.; Liu, S.; Yu, Z.; Wang, Y.-N.; Tan, Z. Y.; Huang, R.-Z.; Lan, Y.; Zhao, Y. Nine-Membered Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond Formation. J. Am. Chem. Soc. 2017, 139, 15304-15307. (c) Yang, L.-C.; Tan, Z. Y.; Rong, Z.-Q.; Liu, R.; Wang, Y.-N.; Zhao, Y. Palladium-Titanium Relay Catalysis Enables Switch from Alkoxide-πAllyl to Dienolate Reactivity for Spiro-Heterocycle Synthesis. Angew. Chem. Int. Ed. 2018, 57, 7860-7864. VECs were also applied on other asymmetric transformations: (d) Cai, A.; Guo, W.; Martínez-Rodríguez, L.; Kleij, A. W. Palladium-Catalyzed Regio-and Enantioselective Synthesis of Allylic Amines Featuring Tetrasubstituted Tertiary Carbons. J. Am. Chem. Soc. 2016, 138, 14194-14197. (e) Khan, A.; Khan, S.; Khan, I.; Zhao, C.; Mao, Y.; Chen, Yan.; Zhang, Y. J. Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols. J. Am. Chem. Soc. 2017, 139, 10733-10741. (14) During the course of this study, Glorius and coworkers reported an enantioselective [5+2] cycloaddition of VECs with enals: Singha, S.; Patra, T.; Daniliuc, C. G.; Glorius, F. Highly Enantioselective [5+2] Annulations through Cooperative N‑Heterocyclic Carbene (NHC) Organocatalysis and Palladium Catalysis. J. Am. Chem. Soc. 2018, 140, 3551-3554. Unlike their elegant work involving the use of both a chiral Pd catalyst and a chiral carbene catalyst, in our work, only a chiral Pd catalyst and visible light are required, and chiral quaternary centers can be formed with high enantioselectivity. (15) (a) Quasdorf, K. W.; Overman, L. E. Catalytic enantioselective synthesis of quaternary carbon stereocentres. Nature 2014, 516, 181-191. (b) Liu, Y.-Y.; Han, S.-J.; Liu, W.-B.; Brian, M. S. Catalytic Enantioselective Construction of Quaternary Stereocenters: Assembly of Key Building Blocks for the Synthesis of Biologically Active Molecules. Acc. Chem. Res. 2015, 48, 740-751. (16) (a) Kumar, P.; Troast, D. M.; Cella, R.; Louie, J. Ni-Catalyzed Ketene Cycloaddition: A System That Resists the Formation of Decarbonylation Side Products. J. Am. Chem. Soc. 2011, 133, 7719-7721. (b) Xiao, Q.; Zhang, Y.; Wang, J.-B. Diazo Compounds and N-Tosylhydrazones: Novel Cross-Coupling Partners in Transition-Metal-Catalyzed Reactions. Acc. Chem. Res. 2013, 46, 236-247. (17) In the following mechanism studies, we found that the light intensity indeed affected the generation of the ketene and the subsequent cycloaddition. Please see the SI for details.
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Graphic Abstract: O
Catalytic Asymmetric [5+2] Cycloadditions O O
O +
O
R
R1 VECs
R3
2
N2 -diazoketones
• room temperature
O seven
Pd 29 examples 42-99% yields 73:27-96:4 er
• visible light irradiation
R2 R3
R1 chiral lactones
• chiral quaternary carbon
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