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Highly Diastereoselective Construction of 6,8-DOBCO Frameworks from Vinylethylene Carbonates via Palladium-Organo Relay Catalysis Rong Zeng, Jun-Long Li, Xiang Zhang, Yan-Qing Liu, Zhi-Qiang Jia, Hai-Jun Leng, Qian-Wei Huang, Yue Liu, and Qing-Zhu Li ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b02598 • Publication Date (Web): 29 Jul 2019 Downloaded from pubs.acs.org on July 29, 2019
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ACS Catalysis
Highly Diastereoselective Construction of 6,8-DOBCO Frameworks from Vinylethylene Carbonates via PalladiumOrgano Relay Catalysis Rong Zeng,† Jun-Long Li,*†,‡ Xiang Zhang,†,‡ Yan-Qing Liu,† Zhi-Qiang Jia,† Hai-Jun Leng,† Qian-Wei Huang,† Yue Liu,† and Qing-Zhu Li*† †
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China ‡ Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China ABSTRACT: The 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) architecture widely exists in a broad spectrum of bioactive natural products, and the development of efficient and convenient protocols to construct this skeleton remains a challenging task. Here, we report a concise synthetic strategy for the single-step construction of 6,8-DOBCO frameworks from simple vinylethylene carbonates and amine-substituted enones. This protocol features a sequential reaction of N-allylic substitution, DielsAlder cyclization, and intramolecular ketalization, which is promoted by metal-organo relay catalysis involving palladium/phosphoric acid or palladium/halogen-bonding catalytic system. Over 50 examples of 6,8-DOBCO derivatives with structural diversity have been facilely achieved with satisfactory synthetic results, including high levels of stereoselectivity, reasonable isolated yield, ample scope in reaction partners, high step-economy, and operational simplicity. KEYWORDS: Dioxabicyclo[3.2.1]octanes, diastereoselective synthesis, relay catalysis, structural diversity, vinylethylene carbonates
pheromones
INTRODUCTION 6,8-dioxabicyclo[3.2.1]octane1 (6,8-DOBCO) represents one of the privileged scaffolds in natural product chemistry, because this skeleton not only constitutes the core structure of various pheromones,2 such as frontalin, brevicomin, and multistriatin, but it is also widely distributed as a subunit in many other structurally complex natural products (Figure 1).3 Consequently, the preparation and creation of such skeletalrelated molecules is of high synthetic and biological interest.4 However, construction of 6,8-DOBCO remains a challenging task due to its unique strained bicyclic acetal structure featuring a one-atom bridge between the five- and sixmembered ring system.4a
Me O
Me O Me O
O H
Me
NaO3SO
O
13
NH2
O
H
Me O H
HO attenol B
Me
Me HO
O
multistriatin
O
Me Me
Me
O OH
Me Me OH
cimigenol
Me Me O
Me
endo-brevicomin
didemniserinolipid B
OH OH
O
Me Me
OH O H
EtO O
O
exo-brevicomin
frontalin
Me
Me O
Me O
OH
O
OH
5
O O
O HO
H
psoracorylifol C
Me
O
OH trichodermatide A
Figure 1. Selected natural products containing 6,8-DOBCO moiety.
Although various strategies and methods have been developed through decades of synthetic endeavors on this target, several longstanding problems, including tedious multi-step synthesis, limited variation in starting materials, and stereoselectivity issues, have yet to be effectively addressed. Thus, the development of smart catalytic technologies and concise synthetic routes to prepare 6,8-DOBCOs from simple and variable substrates is highly desirable.
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Vinylethylene carbonates (VECs) have emerged as versatile building blocks, and they have been extensively exploited in organic synthesis during the last decade.5 Typically, VECs undergo facile decarboxylation in the presence of a palladium catalyst to form zwitterionic π-allyl palladium intermediates I,68 which might either tautomerize to six-membered palladacyclic species9 II or generate dienolate intermediates III10. As shown in Scheme 1a, these in situ-generated reactive intermediates have various functionalities, such as nucleophilic oxygen anions, electrophilic Pd-π-allyl moieties, and electronneutral alkenes. Previous studies mainly focused on exploring the synthetic versatility of VECs by using a single palladium catalytic system, leading to the realization of various interesting transformations, including allylic substitutions, formal cycloadditions, and nucleophilic addition reactions. However, only a part of these functional moieties on VECs was utilized in such single catalytic systems, and the synthetic potential and translational ability have not been fully exploited. For example, the palladium-catalyzed nucleophilic addition to VECs only utilize the high electrophilic palladacyclic fragment II to deliver valuable linear allylic alcohols,9 whereas other functionalities such as the nucleophilic oxygen and alkenes played a minor role in these catalytic reactions. Further decoration of the alcohol products to construct drug-like frameworks and structurally complex compounds often requires additional purification and synthetic steps, which might result in higher production costs. Therefore, designing a catalytic system that can utilize all potential functionalities on VEC substrates in a single-step reaction to create interesting molecules is an attractive, economical, and previously underdeveloped research area. Scheme 1. Maximal utilization of the functionalities on VECs to construct 6,8-DOBCO skeletons via metal-organo relay catalysis. a Reaction positions on VECs in reported Pd-catalyzed transformations 1O
5 3
O O
[Pd]
OH 5
PdL
2 4
II
CO2
3
4
1 O
cyclization or
5
3
allyl-substitution
5
3
branched
linear
PdL
2
HO Nu
1O
1O
O
Nu
allyl-substitution
[3+n]
I
[5+n]
[Pd]
VECs
4
1O 2
5
umpolung
HO
2
5
OHC
3
E
3
O
O
O
relay catalysis
Pd Org
O P O
4
N 5
1O
O
4
O
3
1 6,8-DOBCOs
H N
4
maximal utilization of FGs on VCEs 4 chemical bonds formed in one reaction
N I
Me OTf
interesting 6,8-DOBCO skeleton obtained > 50 examples, up to 95% yield, >19:1 dr
Relay catalysis offers great opportunities to discover exciting chemistry with many advantages over single catalytic systems, such as saving chemicals, time, energy and labor,
O
O
5 3
O
or Me N
Our initial investigations focused on determining an effective palladium/acid dual catalytic system for the assembly of 6,8-DOBCOs from easily accessible vinylethylene carbonate 1a and amine-substituted enone 2a (Table 1). First, we tested various Lewis acids to evaluate the compatibility with Pd(PPh3)4. Although most of them completely inhibited the catalytic activity of the palladium complex (entries 14), Ti(OiPr)4 and FeCl2 promoted the target sequential reaction to deliver 6,8-DOBCO derivative 3a in moderate yields with excellent diastereoselectivities (entries 5 and 6). The results greatly encouraged us to screen additional types of acids to improve the reaction outcome, and we focused on the investigatation of the suitability of Brønsted acids, such as ptoluene sulfonic acid (PTSA), trifluoroacetic acid (TFA) and phosphoric acids PA1PA3. Again, no desired products were generated using such metal-organo catalysts (entries 711). To our delight, a BINOL-derived bulkyl phosphoric acid PA4 proved to be well compatible with this palladium catalytic system, and it provided reasonable yield without reducing diastereoselectivity (entry 12). Subsequently, solvents were further screened based on this palladium/phosphoric acid system, but inferior results were obtained (entries 1317). When the reaction was performed at lower temperature, the isolated yield of 3a slightly decreased (entry 18).15
PdL
2
organocatalyst
OH
RESULTS AND DISCUSSION
Table 1. Screening conditions for the reaction of VEC 1a and enone 2a.a
via
+
alleviating the generation of waste, and maximizing synthetic efficiency. Despite being powerful, some challenges inherent in the relay catalysis, especially the compatibility and cooperativity between different catalysts, make developing elegant and efficient relay catalytic systems highly significant.11 On the basis of the aforementioned motivations and our previous interest in the assembly of biologically interesting skeletons through organocatalysis,12 we report herein a concise method for the construction of 6,8-DOBCO frameworks from simple VECs and amine-substituted enones via metal-organo dual catalysis.13 The present relay catalytic system, which invovles palladium/phosphoric acid or palladium/halogenbonding catalyst,14 enables a sequential reaction of N-allylic substitution, oxo-Diels–Alder cyclization, and intramolecular ketalization. Through this protocol, all the functional groups on VECs maximally participate in the bond-forming reactions, thereby furnishing a broad spectrum of 6,8-DOBCO derivatives with structural diversity.
[4+2]
III b This work: the synthesis of 6,8-DOBCOs from VECs
O
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Ph O
O
+
solvent, 60 °C, 24 h TsHN 2a
Ph 1a
Ph O
Pd(PPh3)4 (5 mol %) cocatalyst (20 mol %) Ts
N
Ph
O 3a
entry
cocatalyst
solvent
yield (%)b
drc
1
BF3 Et2O
DCM
19:1 dr 3m R = Br, 68%, >19:1 dr 3n R = NO2, 80%, >19:1 dr 3o R = Me, 70%, >19:1 dr 3p R = Et, 74%, >19:1 dr 3q R = OMe, 74%, >19:1 dr
R
Unless noted otherwise, the reactions were carried out with 1a (0.15 mmol), 2b (0.1 mmol), Pd(PPh3)4 (5 mol %) and cocatalyt (20 mol %) in solvent (1 mL) at 60 oC for 24 h. b Isolated yield of 3a. c Dr was determined by 1H-NMR analysis of the crude reaction mixture. d the reaction was performed at 50 oC.
a
Cl
O
N
3g R = Br, 74%, >19:1 dr 3h R = OMe, 73%, >19:1 dr
3j 82%, 6:1 dr (43%, >19:1 dr)e
PA4 R = 2,4,6-(iPr)3-C6H2
The generality of 6,8-DOBCO synthesis under optimized conditions was then investigated. As summarized in Table 2, VECs 1 featuring either an electron-donating or electronwithdrawing group on the benzene ring worked well under standard conditions, generating the 6,8-DOBCOs 3a3i in good yields with excellent diastereoselectivities. Heteroaromatic VEC was also a suitable substrate to produce a thienyl product 3j in 82% yield with moderate dr value. Alternatively, the diastereoselective ratio of 3j could be promoted by using TsOH as co-catalyst through a sequential one-pot reaction fashion, which suggests the acids would influence the diastereoselectivity of this cascade transformation16 Next, we examined the reaction of 1a with various enones 2 under optimal conditions. It was found that various enone substrates with different aromatic rings bearing diverse electronic and steric substituents were compatible, thereby giving the corresponding products 3k3u with high levels of isolated yields and diastereose lectivities. The reactions also proceeded well for the furyl or
Ph O Ts
R
Ph O
R PA1
Cl
R
O P
3b R = F, 76%, >19:1 dr 3c R = Br, 75%, >19:1 dr 3d R = Me, 84%, >19:1 dr 3e R = Et, 73%, >19:1 dr 3f R = OMe, 70%, >19:1 dr
Ph O
CCDC 1914720 (3a)
R1
3
R O
3
O
N
2
Ph O N
O
DCM, 60 °C, 24 h
R1
Ts
R2
Pd(PPh3)4 (5 mol %) -PA4 (20 mol%)
R2
Cl
Cl Br
O Ts
O
Ph
O
N
N
Ts
3r R = Cl, 81%, >19:1 dr 3s R = OMe, 78%, >19:1 dr
Ts
3u 75%, >19:1 dr
S
O
O
Ph
O
Ts
3v 84%, >19:1 dr
N
Ph
O
N
Ts
3t 71%, >19:1 dr
O
N
O
Ph
O
Ph O
Ph
O
3w 74%, >19:1 dr
Ph
O
N
Cs
3xf 71%, >19:1 dr
Unless noted otherwise, the reactions were carried out with 1 (0.15 mmol), 2 (0.1 mmol), Pd(PPh3)4 (5 mol %) and PA4 (20 mol %) in DCM (1.0 mL) at 60 oC for 24 h. b Yield of the isolated product. c Dr was determined by 1H-NMR analysis of the crude reaction mixture. d The structure of 3a was determined by X-ray analysis, and the other products were assigned by analogy. e data in parentheses refer to using an another modified condition to obtain higher diastereoselectivity, for details, see SI.16 f Cs: 4-chlorobenzenesulfonyl. a
thienyl substituted enones, and the corresponding 3v and 3w were produced in satisfactory yields. Furthermore, the N-4chlorobenzenesulfonyl-protected aminomethyl enone was tested, and the protecting group had a limited effect on the reaction outcome (3x).
Table 2. Substrate scope for the reactions of VECs 1 with 2.a,b,c
initial
O O Ph
PA4 (20 mol %) DCM, 60 °C
O 1a +
19:1 dr
toluene, 100 °C
Scheme 2. Rediscovery of the optimal reaction conditions of VEC 1a with o-amino chalcone 4a Table 3. Substrate scope for the reactions of VECs 1 with 4a,b,c
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ACS Catalysis O
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
O
O O
+
R
R
3
N H 4
R1
1
Ph O
Pd(PPh3)4 (5 mol %) 2
R3
O
R1
O
N
toluene, rt to 100 °C R3
5
Ph O
Ph
O N Ts 5ad 95%, >19:1 dr
R2
R3
XB1 (20 mol%)
N
R
O
Ts
5b R = F, 94%, 14:1 dr 5c R = Br, 85%, 17:1 dr 5d R = Me, 80%, >19:1 dr 5e R = Et, 86%, >19:1 dr 5f R = OMe, 86%, >19:1 dr
R
Ph O N
5g R = Cl, 95%, >19:1 dr 5h R = Br, 82%, >19:1 dr 5i R = OMe, 54%, >19:1 dr 5j R = 3,4-Cl2, 88%, >19:1 dr
O
Ts CCDC 1914717 (5a)
Ph O
Ph O N
O
N
R
O N
Ph
O
Ts
R
Ph O N Ts
O
N
Ts
Ts 5k 83%, 4:1 dr (76%, >19:1 dr)e
Ph
5x R = Cl, 85%, >19:1 dr 5y R = Br, 80%, >19:1 dr 5z R = Me, 84%, 13:1 dr
Me
O
Ts
5l 61%, 2:1 dr (80%, >19:1 dr)e 5n R = 4-F, 84%, >19:1 dr 5o R = 4-Cl, 91%, >19:1 dr 5p R = 4-Br, 83%, >19:1 dr 5q R = 4-Me, 80%, >19:1 dr 5r R = 4-OMe, 84%, 14:1 dr 5s R = 3-Cl, 70%, >19:1 dr 5t R = 3-OMe, 88%, 10:1 dr 5u R = 2-Cl, 88%, >19:1 dr
Ph O
R
O
Ph O
S
N
5m 63%, 3:1 dr
X
O N Ts
5v X = O, 74%, >19:1 dr 5w X = S, 74%, >19:1 dr
Ph O
Ph N
O
Ts 5aa R = F, 72%, >19:1 dr 5ab R = Br, 81%, >19:1 dr
Ph
O
Ph
O
R
5ac R = SO2Ph, 92%, 11:1 dr 5ad R = Cs, 80%, >19:1 dr
Unless noted otherwise, the reactions were carried out with 1 (0.15 mmol), 4 (0.10 mmol) and Pd(PPh3)4 (5 mol %) in toluene (1.0 mL) at room temperature for 2 h; then halogen-bonding donor XB1 (20 mol %) was added and reaction stirred at 100 oC for 24 h. b Isolated yield. c Dr was determined by 1H-NMR analysis of the crude reaction mixture. d The structure of 3a was determined by X-ray analysis, and the other products were assigned by analogy. e data in parentheses refer to using an another modified condition to obtain higher diastereoselectivity, for details, see SI.16 a
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DOBCOs 5k and 5l in good yields with unsatisfactory diastereoselectivities, and the diastereocontrol of both reactions could also be improved by an alternative catalytic one-pot process using TsOH.16 Notably, an alkyl-substituted VEC could undergo this catalytic transformation to afford 5m in 63% yield, albeit with 3:1 diastereoselective ratio. Importantly, a wide range of o-amino chalcones 4 with various para-, meta- or ortho-substituents with both electron-rich and electron-poor features at the aryl groups were systematically investigated. All the tested reactions proceeded well, and the corresponding products 5n5ad were delivered in a highly efficient and diastereoselective manner. To demonstrate the practicality of these methods, we performed gram-scale reactions of VEC 1a with enones 2a or 4a, and 1.00 grams of 3a and 1.24 grams of 5a were obtained smoothly (Scheme 3a). Synthetic derivatization was also explored to further illustrate the versatility of the products. As shown in Scheme 3b, in the presence of diisobutylaluminum hydride (DIBAL-H), a regioselective reduction of the ketal moiety on 3a afforded the alcohol product 6 in 82% yield.17 The p-toluenesulfonyl N-protecting group of the tetrahydroquinoline on 5a could be easily removed by magnesium powder to yield the product 7, which could be easily oxidized to quinioline 8 by DEAD.18 Moreover, a fresh skeleton 9 with a fused hemiaminal moiety could be rapidly assembled from 7 via a sequential reductive ring-opening and oxidative cyclization reaction. In order to explore the reaction mechanism, several control experiments were performed. 19 As shown in Scheme 4, the reaction of 1a and 2a catalyzed by palladium can afford an Nallylation product 10 in the absence of phosphoric acid catalyst. By increasing the temperature to 60 oC, compound 10 cyclized smoothly to afford the bicyclic dihydropyran 11 through an intramolecular oxo-DielsAlder reaction. Furthermore, 11 could also be directly accessed from 1a and 2a via palladium catalysis under heating condition. In addition, by treatment of 11 with catalytic amount of phosphoric acid PA4 in DCM at 60 oC, the final product 3a could be accessed in high yield. These
To further investigate the generality of this relay catalytic strategy as well as prepare structurally diverse 6,8-DOBCOs, we carefully studied o-amino chalcones as another type of enone substrate. Unfortunately, the initial attempt on the sequential reaction of VEC 1a and enone 4a under the established conditions was unsuccessful. Therefore, we extensively rescreened the conditions (for details, see SI) and found that a halogen-bonding donor XB1 could cooperate with palladium catalyst to trigger the desired cascade reaction, and give the corresponding polycyclic product 5a with excellent results in terms of yield and diastereoselectivity (Scheme 2). With the newly established optimal catalytic reaction condition in hand, we immediately tested the scope and limitation of the palladium/halogen-bonding donor cocatalyzed sequential reaction of VECs 1 and various o-amino chalcones 4. As shown in Table 3, VECs 1 with either electronrich or electron–deficient aryl groups could successfully afford the desired products 5a5j with excellent yields and diastereoselectivities. Naphthyl and heteroarene-substituted 1 were also well-tolerated and delivered the corresponding
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ACS Catalysis a Large-scale synthesis of 3a and 5a
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
O 1a
+
NHTs
Ph
O
Ph
O
Ph O
standard conditions II
Ph
+
N
Ts 3a 75% 1.03 g
2a (0.94 g)
1a
Ph O
standard conditions I
NHTs
Ph
O
N
Ts 5a 83% 1.31 g
4a (1.14 g) b Synthetic transformations of the products
Ph O
(a)
3a
Ts
N
Ph N H O (a), (c) 9 63% (2 steps)
HO 6 82%
Ph O
(b)
5a
Ph O
Ph
N H
Ph
Ph O
(c)
N
O 7 78%
Ph
O
8 67%
Conditions: (a) DIBAL-H, DCM, rt; (b) Mg, MeOH, sonication, 40 oC; (c) DEAD, DCM, rt.
a
Scheme 3. Large-scale experiments and synthetic derivatizationsa O O
O
+ 2a
o
DCM, 60 C, 78%
Ph 1a
Ts
Pd(PPh3)4 DCM, 60 oC 85%
Pd(PPh3)4 DCM, rt 89%
Ts N
O Ph
control experiments
Ph O
Pd(PPh3)4, PA4
HO 10
Ph
O 3a
PA4 DCM 87% 60 oC
Ph O Ph
DCM, 60 oC 94%
Ts Ph
N
N
OH 11
Scheme 4. Control experiments results suggest the overall catalytic transformation probably proceeded through a Pd-catalyzed N-allylic substitution, DA cyclization and PA-catalyzed ketalization domino process. On the basis of the stereo configuration of the final products and the results of control experiments, a plausible mechanism for the Pd/PA co-catalyzed reaction was proposed. As shown in Figure 2, the reaction was initiated by the palladiumcatalyzed decarboxylation of VEC 1a to generate the π-allyl palladium intermediate I, which could further tautomerize to a highly electrophilic six-membered palladacyclic species II. This cyclic intermediate was then trapped by the nucleophilic amino group on 2a to give the allyl alcohol 10. Next, an intramolecular DielsAlder cyclization of the enone and internal alkene moieties occurred with unusual exo selectivity. The resulting dihydropyran 11 was protonated by phosphoric acid catalyst and isomerized to a zwitterionic oxonium, which was trapped by the alcohol to deliver the final product 3a.
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Ts N
O
1a
Pd0
Ph
CO2
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HO 10
O O Ph
PdII
H N
Pd-catalyzed allylic substitution
Ts
II
O Pd
Ts N
OH
Ts
O
I
O
O
Ph
P
O H
N
Ph O
O
Ph O Ph
OH
O P Ph O O H
Ts N PA-catalyzed ketal formation
O
exo-selective
Ph Ph O
II
O Pd
2a Ph
Ts
II
N 11
Ph
OH
O
Ph O
O P
O
O H
Ts
N
3a
Ph
O
Figure 2. Proposed reaction mechanism of the palladium/phosphoric acid relay catalytic reactions
(CIF), 5a (CIF) and 9 (CIF). This material is available free of charge via the Internet at http://pubs.acs.org.
CONCLUSION In summary, we have developed a novel synthetic method for the one-step construction of polycyclic 6,8-DOBCO architecture. By taking advantage of palladium and phosphoric acid dual catalysis, various pyrrolidine fused 6,8-DOBCOs were facilely produced in a highly efficient and diastereoselective manner. Another interesting combination of palladium and halogen-bonding donor catalysts enabled the reaction of VECs with o-amino chalcones to furnish a broad spectrum of 6,8-DOBCOs bearing a tetrahydroquinoline moiety. This metal-organo relay-catalyzed transformation probably proceeds through a sequential reaction of N-allylic substitution, inverse-electron-demand oxo-DielsAlder cyclization, and intramolecular ketalization. Such a dual catalytic system maximally utilizes the functional groups on VECs, and enables the formation of four chemical bonds in a single-step reaction. Further investigations on dual catalysis for VEC transformation to construct interesting skeletons are ongoing in our laboratory, and the results will be reported in due course.
AUTHOR INFORMATION Corresponding Author * E-mail:
[email protected] (J.-L. Li)
[email protected] (Q.-Z. Li)
Notes The authors declare no competing financial interests.
ASSOCIATED CONTENT Supporting Information Complete experimental procedures, characterization of new products, NMR spectra, and Xray crystallographic data for 3a
ACKNOWLEDGMENT Financial support from NSFC (21871031, 21702021 and 81703809), the Science & Technology Department of Sichuan Province (2017JQ0032), “Thousand Talents Program” of Sichuan Province, “Chengdu Talents Program” and the start-up found of Chengdu University is gratefully acknowledged.
REFERENCES (1) (a) Francke, W.; Schroeder, W. Bicyclic Acetals in Systems of Chemical Communication. Curr. Org. Chem. 1999, 3, 407−433. (b) Lenci, E; Menchi, G.; Saldívar-Gonzalez, F. I.; Medina-Franco J. L.; Trabocchi, A. Bicyclic Acetals: Biological Relevance, Scaffold Analysis, and Applications in Diversity-Oriented Synthesis. Org. Biomol. Chem. 2019, 17, 1037−1052. (2) (a) Yus, M.; Ramon, D. J.; Prieto, O. (−)-Frontalin: Synthesis using the Catalytic Enantioselective Addition of Dimethylzinc to a Ketone. Eur. J. Org. Chem. 2003, 2003, 2745−2748. (b) Vanderwel, D.; Oehlschlager, A. C. Mechanism of Brevicomin Biosynthesis from (Z)-6-Nonen-2-one in a Bark Beetle. J. Am. Chem. Soc. 1992, 114, 5081−5086. (c) Berens, U.; Scharf, H.-D. The First Stereoselective Synthesis of Racemic βMultistriatin: A Pheromone Component of the European Elm Bark Beetle Scolytus multistriatus (Marsh.). J. Org. Chem. 1995, 60, 5127−5134. (3) For selected 6,8-DOBCO-containing natural products, see: (a) González, N.; Rodríguez, J.; Jiménez, C. Didemniserinolipids A−C, Unprecedented Serinolipids from the Tunicate Didemnum sp. J. Org. Chem. 1999, 64, 5705–5707. (b) Corsano, S.; Mellor, J. M.; Ourisson, G. The Structure of Cimigenol. Chem. Commun. (London), 1965, 0, 185−186. (c) Tanaka, N.; Suenaga, K.; Yamada, K.; Zheng, S.-Z.; Chen, H.-S.; Uemura, D. Isolation and Structures of Attenols A and B. Novel Bicyclic Triols from the Chinese Bivalve Pinna attenuate. Chem. Lett. 1999, 28, 1025−1026. (d) Yin, S.; Fan, C.-Q.; Dong, L.; Yue, J.-M. Psoracorylifols A–E, Five Novel Compounds with Activity Against Helicobacter Pylori from Seeds of Psoralea Corylifolia. Tetrahedron 2006, 62, 2569−2575. (e) Sun, Y.; Tian, L.; Huang, J.; Ma, H.-Y.; Zheng, Z.; Lv, A.-L.; Yasukawa, K.; Pei, Y.-H. Trichodermatides A−D, Novel Polyketides from the MarineDerived Fungus Trichoderma reesei. Org. Lett. 2008, 10, 393–396. (4) For a review on the synthesis of 6,8-DOBCOs, see: (a) Zhang, W.; Tong, R. Synthetic Approaches To Construct the 6,8-DOBCO Framework in Natural Products. J. Org. Chem. 2016, 81, 2203–2212. For selected examples, see: (b) Schmidt, E. Y.; Tatarinova, I. V.; Semenova, N. V.;
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ACS Catalysis Protsuk, N. I.; Ushakov, I. A.; Trofimov, B. A. Exploring Acetylene Chemistry: A Transition Metal-Free Route to Dienyl 6,8Dioxabicyclo[3.2.1]octanes from Ketones and Acetylenes. J. Org. Chem. 2018, 83, 10272–10280. (c) Trofimov, B. A.; Schmidt, E. Y.; Ushakov, I. A.; Mikhaleva, A. I.; Zorina, N. V.; Protsuk, N. I.; Senotrusova, E. Y.; Skital’tseva, E. V.; Kazheva, O. N.; Alexandrov, G. G.; Dyachenko, O. A. One-Pot Assembly of 7-Methylene-6,8-dioxabicyclo[3.2.1]octanes, Congeners of Frontalin, from Ketones and Acetylene. Eur. J. Org. Chem. 2009, 2009, 5142–5145. (5) For selected recent reviews, see: (a) Gómez, J. E.; Kleij, A. W. Catalytic Nonreductive Valorization of Carbon Dioxide into Fine Chemicals. Adv. Organomet. Chem. 2019, 71, 175–226. (b) Guo, W.; Gómez, J. E.; Cristòfol, À; Xie, J.; Kleij, A. W. Catalytic Transformations of Functionalized Cyclic Organic Carbonates. Angew. Chem., Int. Ed. 2018, 57, 13735−13747. (c) Khan, A.; Zhang, Y. J. Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Electrophiles: Construction of Quaternary Stereocenters. Synlett 2015, 25, 853–860. (6) For selected examples on the [3+2] annulation of VECs, see: (a) Yang, L.; Khan A.; Zheng, R.; Jin, L. Y.; Zhang, Y. J. Pd-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Imines. Org. Lett. 2015, 17, 6230–6233. (b) Khan, A.; Xing, J.; Zhao, J.; Kan, Y.; Zhang, W.; Zhang, Y. J. Palladium-Catalyzed Enantioselective Decarboxylative Cycloaddition of Vinylethylene Carbonates with Isocyanates. Chem.–Eur. J. 2015, 21, 120–124. (c) Khan, A.; Zheng, R.; Kan, Y.; Ye, J.; Xing, J.; Zhang, Y. J. Palladium-Catalyzed Eecarboxylative Cycloaddition of Vinylethylene Carbonates with Formaldehyde: Enantioselective Construction of Tertiary Vinylglycols. Angew. Chem., Int. Ed. 2014, 53, 6439–6442. (d) 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. (e) Khan, I.; Zhao, C.; Zhang, Y. J. Pd-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with 3Cyanochromones. Chem. Commun. 2018, 54, 4708–4711. (f) Liu, K.; Khan, I.; Cheng, J.; Hsueh, Y. J.; Zhang, Y. J. Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with β-Nitroolefins by Cooperative Catalysis of Palladium Complex and Squaramide. ACS Catal. 2018, 8, 11600–11604. For representative examples on the annulation via other type of zwitterionic palladium intermediates, see: (g) Punna, N.; Das, P.; Gouverneur, V.; Shibata, N. Highly Diastereoselective Synthesis of Trifluoromethyl Indolines by Interceptive Benzylic Decarboxylative Cycloaddition of Nonvinyl, Trifluoromethyl Benzoxazinanones with Sulfur Ylides under Palladium Catalysis. Org. Lett. 2018, 20, 1526–1529. (h) Punna, N.; Harada, K.; Zhou, J.; Shibata, N. Pd-Catalyzed Decarboxylative Cyclization of Trifluoromethyl Vinyl Benzoxazinanones with Sulfur Ylides: Access to Trifluoromethyl Dihydroquinolines. Org. Lett. 2019, 21, 1515–1520. (7) For selected examples on the [5+n] annulation of VECs, see: (a) Yang, L. C.; Rong, Z. Q.; Wang, Y. N.; Tan, Z. Y.; Wang, M.; Zhao, Y. Construction of Nine-Membered Heterocycles through PalladiumCatalyzed 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. Ninemembered BenzofuranFused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond Formation. J. Am. Chem. Soc. 2017, 139, 15304–15307. (c) Yuan, C.; Wu, Y.; Wang, D.; Zhang, Z.; Wang, C.; Zhou, L.; Zhang, C.; Song, B.; Guo, H. Formal [5+3] Cycloaddition of Zwitterionic Allylpalladium Intermediates with Azomethine Imines for Construction of N,O-Containing Eight-Membered Heterocycles. Adv. Synth. Catal. 2018, 360, 652–658. (d) Das, P.; Gondo, S.; Nagender, P.; Uno, H.; Tokunaga, E.; Shibata, N. Access to Benzo-Fused NineMembered Heterocyclic Alkenes with a Trifluoromethyl Carbinol Moiety via a Double Decarboxylative Formal Ring-Expansion Process under Palladium Catalysis. Chem. Sci. 2018, 9, 3276−3281. (e) Yang, Y.; Yang, W. Divergent Synthesis of N-heterocycles by Pd-Catalyzed Controllable Cyclization of Vinylethylene Carbonates. Chem. Commun. 2018, 54, 12182−12185. (f) Zhao, H. W.; Du, J.; Guo, J. M.; Feng, N.-N.; Wang, L.R.; Ding, W.-Q.; Song, X.-Q. Formal [5+2] Cycloaddition of Vinylethylene Carbonates to Oxazol-5-(4H)-ones for the Synthesis of 3,4Dihydrooxepin-2(7H)-ones. Chem. Commun. 2018, 54, 9178−9181. (g) 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, 3551−3354. (h) Wei, Y.; Liu, S.; Li, M. M.; Li, Y.; Lan, Y.; Lu, L.-Q.; Xiao, W.-J. Enantioselective Trapping of Pd-Containing 1,5-Dipoles by Photogenerated Ketenes: Access to 7-Membered Lactones Bearing Chiral Quaternary Stereocenters. J. Am. Chem. Soc. 2019, 141, 133−137. (8) For the branched-selective allylic substitution with VECs, see: (a) Cai, A.; Guo, W.; Martínez-Rodríguez, L.; Kleij, A. W. PalladiumCatalyzed Regio- and Enantioselective Synthesis of Allylic Amines Featuring Tetrasubstituted Tertiary Carbons. J. Am. Chem. Soc. 2016, 138, 14194−14197. (b) Khan, A.; Khan, S.; Khan, I.; Zhao, C.; Mao, Y.; Chen, Y.; 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. (c) Quan, M.; Butt, N.; Shen, J.; Shen, K.; Liu, D.; Zhang, W. The Synthesis of Chiral β-Aryl-α,βunsaturated Amino Alcohols via a Pd-Catalyzed Asymmetric Allylic amination. Org. Biomol. Chem. 2013, 11, 7412−7419. (d) Zhang, Y.J.; Yang, J. H.; Kim, S. H.; Krische, M. J. anti-Diastereo- and Enantioselective Carbonyl (Hydroxymethyl)allylation from the Alcohol or Aldehyde Oxidation Level: Allyl Carbonates as Allylmetal Surrogates. J. Am. Chem. Soc. 2010, 132, 4562−4563. (e) Trost, B. M.; Aponick, A. PalladiumCatalyzed Asymmetric Allylic Alkylation of meso- and dl-1,2Divinylethylene Carbonate. J. Am. Chem. Soc. 2006, 128, 3931−3933. (9) For the linear-selective allylic substitution with VECs: (a) Guo, W.; Martínez-Rodríguez, L.; Kuniyil, R.; Martin, E.; Escudero-Adán, E. C.; Maseras, F.; Kleij, A. W. Stereoselective and Versatile Preparation of Triand Tetrasubstituted Allylic Amine Scaffolds under Mild Conditions. J. Am. Chem. Soc. 2016, 138, 11970−11978. (b) Guo, W.; MartínezRodríguez, L.; Martin, E.; Escudero-Adán, E. C.; Kleij, A. W. Highly Efficient Catalytic Formation of (Z)-1,4-But-2-ene Diols using Water as a Nucleophile. Angew. Chem., Int. Ed. 2016, 55, 11037−11040. (c) Xie, J.; Guo, W.; Cai, A.; Escudero-Adán, E. C.; Kleij, A. W. Pd-Catalyzed Enantio- and Regioselective Formation of Allylic Aryl Ethers. Org. Lett. 2017, 19, 6388−6391. (d) Crisòfol, À.; Escudero-Adán, E. C.; Kleij, A. W. Palladium-Catalyzed (Z)-Selective Allylation of Nitroalkanes: Access to Highly Functionalized Homoallylic Scaffolds. J. Org. Chem. 2018, 83, 9978−9990. (e) Wei, X.; Liu, D.; An, Q.; Zhang, W. Hydrogen-Bond Directed Regioselective Pd-Catalyzed Asymmetric Allylic Alkylation: The Construction of Chiral α-Amino Acids with Vicinal Tertiary and Quaternary Stereocenters. Org. Lett. 2015, 17, 5768−5771. (f) Deng, L.; Kleij, A. W.; Yang, W. Diversity-Orientated Stereoselective Synthesis through Pd-Catalyzed Switchable Decarboxylative C-N/C-S Bond Formation in Allylic Surrogates. Chem.−Eur. J. 2018, 24, 19156−19161. (g) Miralles, N.; Gómez, J. E.; Kleij, A. W.; Fernández, E. CopperMediated SN2′ Allyl-Alkyl and Allyl-Boryl Couplings of Vinyl Cyclic Carbonates. Org. Lett. 2017, 19, 6096−6099. (10) For the umpolung chemistry of VECs, see: (a) Guo, W.; Kuniyil, R.; Gómez, J. E.; Maseras, F.; Kleij, A. W. A Domino Process toward Functionally Dense Quaternary Carbons through Pd-Catalyzed Decarboxylative C(sp3)–C(sp3) Bond Formation. J. Am. Chem. Soc. 2018, 140, 39813987. (b) Yang, L. C.; Tan, Z. Y.; Rong, Z.-Q.; Liu, R.; Wang, Y.-N.; Zhao, Y. Palladium-Titanium Relay Catalysis Enables Switch from Alkoxide-π-allyl to Dienolate Reactivity for Spiro-Heterocycle Synthesis. Angew. Chem., Int. Ed. 2018, 57, 7860. (c) Wang, H.; Qiu, S.; Wang, S.; Zhai, H. Pd-Catalyzed Umpolung of π–Allylpalladium Intermediates: Assembly of All-Carbon α-Vinyl Quaternary Aldehydes through C(sp3)– C(sp3) Coupling. ACS Catal. 2018, 8, 1196011965. (11) For selected reviews on relay catalysis, see: (a) Fogg, D. E.; dos Santos, E. N. Tandem Catalysis: A Taxonomy and Illustrative Review. Coord. Chem. Rev. 2004, 248, 2365−2379. (b) Patil, N. T.; Shinde, V. S.; Gajula, B. A One-Pot Catalysis: The Strategic Classification with Some Recent Examples. Org. Biomol. Chem. 2012, 10, 211−224. (c) Patil, N. T.; Shinde, V. S.; Gajula, B. A One-Pot Catalysis: the Strategic Classification with Some Recent Examples. Org. Biomol. Chem. 2012, 10, 211−224. (d) Zhou, J. Recent Advances in Multicatalyst Promoted Asymmetric Tandem Reactions. Chem.−Asian J. 2010, 5, 422−434. (12) (a) Li, Q.; Zhou, L.; Shen, X.-D.; Yang, K.-C.; Zhang, X.; Dai, Q.-S.; Leng, H.-J.; Li, Q.-Z.; Li, J.-L. Stereoselective Construction of Halogenated Quaternary Carbon Centers by Brønsted Base Catalyzed [4+ 2] Cycloaddition of α‐Haloaldehydes. Angew. Chem., Int. Ed. 2018, 57, 1913−1917. (b) Li, J.-L.; Fu, L.; Wu, J.; Yang, K.-C.; Li, Q.-Z.; Gou, X.-J.; Peng, C.; Han, B.; Shen, X.-D. Highly Enantioselective Synthesis of Fused
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Bicyclic Dihydropyranones via Low-loading N-heterocyclic Carbene Organocatalysis. Chem. Commun. 2017, 53, 6875−6878. (c) Li, Q.-Z.; Zhang, X.; Zeng, R.; Dai, Q.-S.; Liu, Y.; Shen, X.-D.; Leng, H.-J.; Yang, K.C.; Li, J.-L. Direct Sulfide-Catalyzed Enantioselective Cyclopropanations of Electron-Deficient Dienes and Bromides. Org. Lett. 2018, 20, 3700−3704. (d) Li, J.-L.; Dai, Q.-S.; Yang, K.-C.; Liu, Y.; Zhang, X.; Leng, H.-J.; Peng, C.; Huang, W.; Li, Q.-Z. Construction of Azepino[2, 3b]indole Core via Sulfur Ylide Mediated Annulations. Org. Lett. 2018, 20, 7628−7632. (e) Yang, K.-C.; Li, Q.-Z.; Liu, Y.; He, Q.-Q.; Liu, Y.; Leng, H.-J.; Jia, A.-Q.; Ramachandran, S.; Li, J.-L. Highly Stereoselective Assembly of α-Carbolinone Skeletons via N-Heterocyclic CarbeneCatalyzed [4 + 2] Annulations. Org. Lett. 2018, 20, 7518−7521. (13) For selected reviews on the metal/organo dual catalysis, see: (a) Chen, D.-F.; Han, Z.-Y.; Zhou, X.-L.; Gong, L.-Z. Asymmetric Organocatalysis Combined with Metal Catalysis: Concept, Proof of Concept, and Beyond. Acc. Chem. Res. 2014, 47, 2365−2377. (b) Du, Z.; Shao, Z. Combining Transition Metal Catalysis and Organocatalysis–an Update. Chem. Soc. Rev. 2013, 42, 1337−1378. (c) Rueping, M.; Dipl.Chem., R. M. K.; Atodireser, I. Unifying Metal and Brønsted Acid Catalysis–Concepts, Mechanisms, and Classifications. Chem.−Eur. J. 2010, 16, 9350−9365. (d) Wu, X.; Li, M.; Gong, L. Asymmetric Relay Catalysis Reaction Consisting of Metal Complex and Chiral Phosphoric Acids. Acta Chim. Sin. 2013, 71, 1091–1100. (14) For selected palladium/phosphoric acid catalyzed reactions, see : (a) Banerjee, D.; Junge, K.; Beller, M. Cooperative Catalysis by Palladium and a Chiral Phosphoric Acid: Enantioselective Amination of Racemic Allylic Alcohols. Angew. Chem., Int. Ed. 2014, 53, 1304913053. (b) Zhang, J. Origins of the Enantioselectivity of a Palladium Catalyst with BINOL– Phosphoric Acid Ligands. Org. Biomol. Chem. 2018, 16, 80648071. For selected examples on halogen-bond catalyzed transformations, see: (c) Chan, Y.-C.; Yeung, Y.-Y. Halogen-Bond Catalyzed Bromocarbo-
cyclization. Angew. Chem., Int. Ed. 2018, 57, 3483. (d) Heinen, F.; Engelage, E.; Dreger, A.; Weiss, R.; Huber, S. M. Iodine(III) Derivatives as Halogen Bonding Organocatalysts. Angew. Chem., Int. Ed. 2018, 57, 3830. (e) Gliese, J.-P.; Jungbauer, S. H.; Huber, S. M. A HalogenBonding-Catalyzed Michael Addition Reaction. Chem. Comm. 2017, 53, 1205212055. (f) Jungbauer, S. H.; Huber, S. M. Cationic Multidentate Halogen-Bond Donors in Halide Abstraction Organocatalysis: Catalyst Optimization by Preorganization. J. Am. Chem. Soc. 2015, 137, 1211012120. (g) Takeda, Y.; Hisakuni, D.; Lin, C.-H.; Minakata, S. 2Halogenoimidazolium Salt Catalyzed Aza-Diels–Alder Reaction through Halogen-Bond Formation. Org. Lett. 2015, 17, 318321. (15) For more studies on condition screening, see the Supporting Information. (16) The diastereselectivities of these products (3j, 5k and 5l) can be improved by an alternative protocol; for details on this procedure, see Supporting Information. (17) Kotsuki, H.; Ushio, Y.; Kadota, I.; Ochi, M. Stereoselective Reduction of Bicyclic Ketals. An Efficient Synthesis of (−)-(R,R)-(cis-6Methyltetrahydropyran-2-yl)acetic Acid, an Enantiomer of Civet Cat Constituent. Chem. Lett. 1988, 17, 927930. (18) Bang, S. B.; Kim, J. Efficient Dehydrogenation of 1,2,3,4Tetrahydroquinolines Mediated by Dialkyl Azodicarboxylates. Synthetic Commun. 2018, 16, 80648071. (19) For more control experiments on the catalytic reaction, see Supporting Information.
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ACS Catalysis
Table of Contents N-allylation
ketalization
O
O O
IEDDA
relay catalysis
O
Pd
+
O
Org
H N
N
O
6,8-DOBCOs
4 chemical bond formation & two 4o stereocenters one-step construction of 6,8-DOBCO skeleton maximal utilization of FGs on VCEs
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> 50 examples up to 95% yield up to >19:1 dr
