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Pd-Catalyzed Umpolung of #-Allylpalladium Intermediates: Assembly of All-Carbon #-Vinyl Quaternary Aldehydes through C(sp3)-C(sp3) Coupling Huifei Wang, Shuxian Qiu, Sasa Wang, and Hongbin Zhai ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b03814 • Publication Date (Web): 09 Nov 2018 Downloaded from http://pubs.acs.org on November 9, 2018
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ACS Catalysis
Pd-Catalyzed Umpolung of π-Allylpalladium Intermediates: Assembly of All-Carbon α-Vinyl Quaternary Aldehydes through C(sp3)-C(sp3) Coupling Huifei Wang,†,‡,‖ Shuxian Qiu,†,‖ Sasa Wang,† and Hongbin Zhai*,†,§ †State
Key Laboratory of Chemical Oncogenomics, Shenzhen Engineering Laboratory of Nano Drug Slow-Release, Peking University Shenzhen Graduate School, Shenzhen 518055, China ‡School of Materials Science and Chemical Engineering, Ningbo University, Ningbo 315211, China §Collaborative
Innovation Center of Chemical Science and Engineering, Tianjin 300071, China
KEYWORDS: all-carbon quaternary center, decarboxylation, VECs, umpolung, palladium, allylic alkylation ABSTRACT: Construction of sterically congested all-carbon quaternary centers represents a formidable challenge in synthetic chemistry. The method described herein provides direct and facile access to a series of structurally diverse and synthetically useful aliphatic aldehydes, bearing an all-carbon α-vinyl quaternary center and a 1,5-diene functionality, through Pd-catalyzed umpolung of vinylethylene carbonates (VECs). The reaction features electrophilic-to-nucleophilic reactivity O L R "Pd" O + Pd reversal of the VEC-derived π-allyl-palladium umpolung E+ O O O intermediate via an unusual β-hydride AcO R R CHO CO2 R elimination process and the resultant enolate is chemoselectively coupled with allylic acetate to VECs nucleophile electrophile dienolate form an α-vinyl aldehyde embedded with an allhigh chemoselectivity high functional diversity all-carbon quaternary center carbon quaternary center.
All-carbon quaternary centers with four different carbon functional groups exist widely in biologically intriguing and architecturally fascinating natural products as well as many FDA-approved pharmaceuticals (Figure 1).1 Although synthetic chemists have made tremendous efforts on developing novel methodologies to access all-carbon quaternary centers in a direct, efficient, and highly selective manner,2,3 there still remain daunting challenges to the construction of acyclic allcarbon α-vinyl quaternary aldehydes. The conventional methods to those motifs usually required tedious steps and only limited direct strategies have been reported.4,5 Consequently, it is essential to develop novel approaches to rapidly construct allcarbon α-vinyl quaternary aldehydes. Organic cyclic carbonates, particularly vinylethylene carbonates (VECs), have been witnessed in recent years as privileged motifs enabling facile access to structurally diverse and biologically potential building blocks.6 Notably, the research groups of Zhang,7 Kleij, 8 Zhao,9 Glorius10 and others11 have accomplished a wide variety of Pd-catalyzed decarboxylative transformations of VECs (Scheme 1). The common π-allylpalladium intermediate I, which contains a nucleophilic alkoxide and an electrophilic π-allyl-Pd species can serve as 1,3- or 1,5-dipole, leading to [3+2],7b-e,9c [5+2],10,11c [5+3],11b or [5+4] cycloaddition9a-b,11a with high
H SN N S
Me H N O
H
O
Me SN NS O Me N H O H 11,11'-Dideoxyverticillin A cytotoxicity
Me
H
O
H N
O
N
O
Strychnine toxicity
O
O
HBr
H
MeO
MeN HO
NH2
N H
O
Dextromethorphan Cytadre cough suppressant adrenocortical inhibitor
N
Verapamil calcium channel blocker N
Et O
MeN
MeO
Razadyne AChE inhibitor
OMe
N
MeO
N
O
R = H, Morphine R = Me, Codeine analgesic
O O Halenaquinone PI3K inhibitor
MeO
MeO OR OH
O
Me
NH2 Leritine analgesic
HO CO2Et
N Talwin analgesic
Figure 1. Bioactive Natural Products and FDA-approved Drugs with All-Carbon Quaternary Centers. diastereo- or enantioselectivity (Scheme 1, eq 1). Alternatively, the π-allylpalladium intermediate I can also undergo substitution at the terminal or internal position with certain nucleophile, forging a new C-C,8c C-N,8a,d C-O,7a,8e,g C-S8b or CB bond8f (Scheme 1, eq 2). Compared with the wealth of reports on VECs employed as an electrophile, the application of VECs
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as a nucleophile is rare. Inspired by Trost’s pioneering discovery on β-H elimination of π-allylpalladium intermediate and umpolung of the reactivity12 (Scheme 1, eq 3) and due to our continuing interest on novel decarboxylation strategies,13,14 we launched a research program on the palladium-catalyzed reaction of VEC with allylic acetate as an electrophile. We envisioned that VEC might display reversed reactivity and act as a carbon-based nucleophile upon β-H elimination12,15 of the π-allyl-Pd intermediate I, through which electrophilic π-allylPd intermediate I may be converted into nucleophilic dienolate II. Note that during our current studies, the groups of Kleij8c and Zhao9c disclosed their elegant work on Pd-catalyzed umpolung of VECs in accomplishing homodimerization and formal [4+2] cycloaddition, respectively (Scheme 1, eq 4), representing the only two reports invloving reversed reactivity of VECs to date. We herein describe our discovery of Pdcatalyzed umpolung of VECs followed by allylation to forge all-carbon α-quaternary aldehydes with high chemoselectivity and good regioselectivity. Reactions of VECs: serving as an electrophile (common) O
L
"Pd"
O
R
CO2
(1,3- or 1,5-dipole) -allyl-Pd intermediate I nucleophile electrophile
VECs
Nu HO or
HO Ph
while promising result was observed when the reaction was performed at 50 ºC (entries 5 and 6). Considerable improvement, with complete suppression of homodimer 5 and acetate 6, was noted when the reaction was conducted at 100 ºC but the yield of the product was slightly decreased at 120 ºC (entries 7 and 8). The reaction Table 1. Optimization of Reaction Conditions O
Pd cat. (2.5 mol %) L (7.5 mol %)
O O
+ AcO
Me Cy
O
Cy P L3
Ph
3a
4
OH
Cy
Ph
O
PPh2
PPh2
PPh2
L1
Ph
PPh2 L2
CHO 5
PPh2 PPh2 L4
Me
CHO
2a Me
OHC
+
THF (0.2 M), T, sealed-tube
Ph
1a
Ph
+
HO
OAc Ph 6
entr y
Pd cat.
L
T (ºC)
3a
3a:4:5:6
1b
Pd2dba3•CHCl3
L1
rt
29
34:37:12:17
2b
Pd(OAc)2/bissulfoxide
L1
rt
34
41:39:11:19
3b
Pd(O2CCF3)2
L1
rt
25
31:48: 9:12
4b
Pd(PPh3)4
L1
rt
31
36:31:14:19
5b
Pd(OAc)2/bissulfoxide
L1
0
20
26:16:nd:58
6b
Pd(OAc)2/bissulfoxide
L1
50
43
45:50: 5:nd
7b
Pd(OAc)2/bissulfoxide
L1
100
62
73:27:nd:nd
8b
Pd(OAc)2/bissulfoxide
L1
120
58
73:27:nd:nd
9
Pd(OAc)2/bissulfoxide
L1
100
74
80:20:nd:nd
10c
Pd(OAc)2/bissulfoxide
L1
100
73
77:23:nd:nd
11d
Pd(OAc)2/bissulfoxide
L1
100
65
70:30:nd:nd
12
Pd(tBu3P)2
L1
100
76
87:13:nd:nd
13
Pd(tBu3P)2
L2
100
38
52:48:nd:nd
14
Pd(tBu3P)2
L3
100
31
39:61:nd:nd
15
Pd(tBu3P)2
L4
100
NR
1)
Pd
O
O R
[3+2], [5+2], [5+3] or [5+4] cycloaddition
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Nu
2) R
nucleophilic addition
Reactions of VECs: serving as a nucleophile (RARE) 3) Trost's early discovery: H Ph
"Pd"
OCO2Me OCO2Me
Ph
DMSO
Ph
L
OCO2Me
Pd
-H elimination
L
Ph
O
OCO2Me
4) Kleij's and Zhao's work
O
O Ph
CHO
homodimerization
O O
+
R
O
Ph
O Ph
Kleij
5) This work
O
O OH Ph
O
OH Ph
palladium-titanium relay catalysis Zhao
L
"Pd"
Pd
O CO2
VECs complete chemoselectivity
H
R
umpolung
E+
-
O
AcO
R
O Ph
R CHO
dienolate II high functional diversity
all-carbon quaternary center
Scheme 1. Pd-Catalyzed Umpolung of VECs We commenced our studies with the reaction of phenylsubstituted vinylethylene carbonate (1a) with 2 equiv of allylic acetate (2a) using Pd2dba3•CHCl3 (2.5 mol %) as the precatalyst and DPEPhos (L1) (7.5 mol %) as a ligand in THF at room temperature (Table 1, entry 1). Gratifyingly, the desired α-quaternary aldehyde (3a), was obtained in 29% yield, accompanied by the enal 4, the homodimerization by-product 5, and the acetate 6. The formation of the first three compounds (3a, 4, 5) implied that the reactivity of VEC had been dominantly reversed as anticipated. Screening of the palladium catalysts revealed that White’s catalyst16 perform better than Pd(PPh3)4, Pd2dba3•CHCl3, or Pd(O2CCF3)2 (entries1-4). The transformation was found to be sensitive to the reaction temperature (entries 5-8). The reaction preferentially gave the acetate 6 as the major product at a lower temperature (0 ºC),
aReaction
optimization was performed using 0.2 mmol of 1a and 0.6 mmol of 2a in THF for 4 h unless noted otherwise. Yields were determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard. b2a (0.4 mmol), 12 h. cNa2SO4 (0.5 equiv) was added. dProton sponge (1.0 equiv) was added. Pd2dba3•CHCl3 = tris(dibenzylideneacetone)dipalladium(0) chloroform adduct. Pd(OAc)2/bis-sulfoxide = White’s catalyst. DPEphos (L1) = oxydi-2,1-phenylene)bis(diphenylphosphine. Proton sponge = 1,8bis(dimethylamino)naphthalene.
efficiency was further enhanced by higher loading of acetate 2a (3 equiv) and shorter reaction time (4 h) (entry 9). Addition of Na2SO4 or proton sponge had no effect (entries 10 and 11). To our delight, replacement of White’s catalyst with more electron-
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ACS Catalysis rich and sterically hindered Pd(tBu3P)2 increased the yield of 3a to 76% (entry 12). Ultimately, upon testing a series of other ligands, DPEphos (L1) was identified as the optimal one (entries 13-15).17 O
Pd(tBu3P)2 (2.5 mol %) DPEPhos (7.5 mol %)
O O
+ AcO
CHO
+
THF, 100 °C, 4 h sealed-tube
Het 1
CHO
Me
Ar
Het
2a
3
4 (minor)
Aromatic Moiety CHO
CHO
CHO
CHO
R
CF3
CO2Me
Me 3a, R = H, 72% 3b, R = Me, 80% 3c, R = Et, 62%b 3d, R = tBu, 53%b 3e, R = Ph, 60% 3f, R = OMe, 58% 3g, R = OBn, 58% 3h, R = SMe, 76% 3i, R = F, 63% 3j, R = Cl, 79%
3k, 70%
CHO
3l, 73%
3m, 61%
CHO
CHO
O OMe
Me
Me
MeO
OMe OMe
3o, 58%b
3n, 69%
Vinyl Moiety
CHO
CHO
CHO
c
S
SMe 7a, 58%
OMe
SMe
SMe
7b, 57%
7c, 64% OH
CHO
F
3w, 78%
CHO
CHO
O
N
3ab, 58%
3ac, 61%
Cl
OMe
3x, 75%
OMe 3aa, 60%
CHO
CHO
R 3y, R = Me, 60% 3z, R = Cl, 75%
7
CHO
S
CHO
S
THF, 100 °C, 4 h sealed-tube
SMe
S
O
3v, 61%
2'
OH
O O 3u, 63%
1h
Ar
Me
3t, 63%
CHO
OH
SMe
AcO
CHO
Heterocyclic Moiety CHO
+
CHO
Pd(tBu3P)2 (5 mol %) DPEPhos (15 mol %)
Me
3s, 63%
3r, 52%
Ar
Ph
OMe 3q, 81%
O O
3p, 74%
CHO CHO
explored (Scheme 2). Substrates with an either electrondonating (3b-3h) or electron-withdrawing (3i-3l) group at the para position of the aromatic ring were compatible with the reaction conditions, giving the desired products in moderate to good yields. Additionally, m-substitution (3m, 3n), multisubstitution (3o, 3p), or more conjugation (3q-3s) of the aryl rings were all well-tolerated. Of particular interest, the reaction of phenylvinyl substituted carbonate (3t) also proceeded smoothly, producing the product in a comparable yield. In order to further investigate the tolerance of structural diversity of the transformation, a broad range of heteroaromatic rings were embedded into the substrates and it was found that heteroaryl carbonates, those bearing a furyl, thienyl, benzofuryl, benzothienyl, or pyridyl group were all competent substrates (3u-3ac). It is noteworthy that our method was also applicable to a late-stage diversification of structurally intricate molecules. The estrone analogue 3ad for example, reacted effectively and furnished the product in a synthetically useful yield, although higher catalyst loading and temperature were found to be necessary.
SMe
SMe
SMe
7d, 44%b
7e, 60%
7f, 52%b
Scheme 3. Substrate Scope. a General reaction conditions: 1h (0.2 mmol), 2' (0.6 mmol), Pd(tBu3P)2 (5 mol %), DPEPhos (15 mol %), 100 º C, 4 h. Isolated yields. b Yield of the corresponding alcohol product over the two steps including reduction with NaBH4.
Late-Stage Diversification of Complex Molecule Me OMe H OHC
H
H
estrone analogue 3ad 50%b
Scheme 2. Substrate Scope. a General reaction conditions: 1 (0.2 mmol), 2a (0.6 mmol), Pd(tBu3P)2 (2.5 mol %), DPEPhos (7.5 mol %), 100 ºC, 4 h. Isolated yields. b Pd(tBu3P)2 (5 mol %), DPEPhos (15 mol %), 110 ºC. c Yield of the corresponding alcohol product over the two steps including reduction with NaBH4. With the optimized conditions secured, we focused on examination of the scope of the substrates in the Pd-catalyzed umpolung of VECs. Various substituted carbonates were first
Next, we explored the scope of the allylic acetate partners with VEC 1h (Scheme 3).18 Under slightly reoptimized conditions with higher catalyst loading, branched arylsubstituted allylic acetates19 carrying either electron-rich (7a7d) or electron-deficient (7e-7f) groups showed good tolerance and provided single linear product with exclusive E-selectivity, implying that the nucleophilic addition take place preferentially at the less sterically hindered terminal position of the π-allyl-Pd intermediate. To demonstrate the practicality of the method, a gram-scale experiment was performed, in which a comparable yield was observed for the generation of α-quaternary aldehyde 3q (Scheme 4). The synthetic utility of the obtained α-quaternary aldehyde 3q was then extensively demonstrated in five types of representative derivatizations. First, Seyferth-Gilbert
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homologation of the aldehyde furnished alkyne 8a smoothly in 65% yield. The aldehyde could then be converted directly into the carboxylic ester 8b and the hydrazone 8c under mild conditions in excellent yields.20 The structure of hydrazone 8c was unambiguously confirmed by single crystal X-ray diffraction analysis.21 Next, one-step reductive amination of the aldehyde 1q (4.75 mmol) + 2a
2-Naph
standard [gram-scale] condition
CHO
e)
8e, 82% (Z:E = 1.4:1)
a)
8a, 65%
CHO
Co
3q 0.931 g (83%)
b)
CO2Me 2-Naph 8b, 92%
2-Naph pe
NHPMB
d) reduc ti amin ve ation
2-Naph 8d, 77%
c) NNHTs 2-Naph [X-ray]
8c, 87%
Scheme 4. Gram-scale Synthesis and Representative Derivatizations of 3q. Reagents and conditions: a) Bestmann reagent (dimethyl (diazomethyl)phosphonate), MeOH, 0 º C→rt, 0.5 h; b) I2, KOH, MeOH, 0 ºC→rt, 0.5 h; c) TsNHNH2, Na2SO4, MeOH, rt, 3 h; d) PMBNH2, Na2SO4, DCE; NaBH(OAc)3; e) mw, toluene, 150 ºC, 7 h. O
CHO
O O 1
Pd
Ph
CO2
(0)
Ph 3
HOAc
AcO
L L Pd
O H
Pd(0) O
Ph
OAc
I Pd L
L L Pd
H
Ph IV OAc
L III OHC
OAc
-H
eli
m
HO
in
at
io n
6 Ph (by-product)
A plausible mechanism of the Pd-catalyzed decarboxylative generation of all-carbon α-quaternary aldehydes is proposed in Scheme 5. On one hand, the π-allyl-Pd intermediate I22 is initially generated from the vinylethylene carbonate 1 in the presence of Pd(0) by oxidative addition, accompanied by CO2 extrusion. The electrophilic π-allyl-Pd intermediate I then undergoes β-H elimination,12,15 delivering the nucleophilic dienolate II. The palladium catalyst can either dissociate, liberating the dienolate and regenerating Pd(0) as shown below, or it can bind to the dienote II to undergo nucleophilic addition prior to dissociation and catalyst regeneration. On the other hand, π-allyl-Pd complex III, formed in situ from allyl acetate, could be trapped by the dienolate II, furnishing the complex IV with a newly-formed all-carbon quaternary center. Finally, dissociation of complex IV delivers the aldehyde 3 with simultaneous regeneration of the Pd(0) catalyst. As a side reaction, nucleophilic addition of the dienolate II to π-allyl-Pd intermediate I furnishes the homodimeric by-product 5.8c In addition, protonation of dienolate II followed by isomerization could generate the enal 4. The by-product 6 can be formed by nucleophilic addition of acetate anion to the π-allyl-Pd intermediate I, similar to previously reported nucleophilic addition.6a In summary, by simply reacting vinyl cyclic carbonate with allylic acetate in the presence of the sterically hindered Pd(tBu3P)2 catalyst, we have accomplished a rare but useful variant of Pd-catalyzed decarboxylative umpolung of VECs providing direct access to a broad series of structurally diverse and synthetically useful all-carbon α-vinyl quaternary aldehydes. Given the long-standing challenges in construction of all-carbon quaternary centers and the robustness of the novel and efficient decarboxylative umpolung of VECs, it can be anticipated with confidence that this protocol would enhance synthetic utilities in the assembly of a wide range of architecturally complex and bioactive building blocks.
ASSOCIATED CONTENT The Supporting Information is available free of charge on the ACS Publications website. Experimental procedures and characterization data for all new compounds (PDF) X-ray crystallographic data for 8c (CIF)
Me
AUTHOR INFORMATION
Ph 4 (by-product)
Corresponding Author
H+
OAc
Page 4 of 7
*E-mail:
[email protected].
O Ph
II
Author Contributions
I
‖ These
homodimer 5 (by-product)
authors contributed equally.
Scheme 5. Catalytic Cycle of the Pd-Catalyzed Umpolung of VECs.
Notes
afforded the corresponding amine 8d in 77% yield. In addition, microwave mediated Cope rearrangement of the 1,5-diene 3q took place at 150 ºC, providing the enals 8e (Z:E = 1.4:1) in 82% combined yield.
ACKNOWLEDGMENT
The authors declare no competing financial interest.
We thank the Shenzhen Science and Technology Innovation Committee (JCYJ20150529153646078 and JSGG20160229150510483) and NSFC (21871018, 21732001,
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ACS Catalysis 21702010, and 21672017) for financial support. We are grateful to Prof. Fayang Qiu of GIBH, CAS for enlightening discussions.
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J. Enantioselective Route to Aryl(1,3-butadien-2-yl)methanols: Formal Synthesis of (-)-Sporochnol A. Heterocycles 2009, 77, 249-253. (d) Kumar, R.; Halder, J.; Nanda, S. Asymmetric Total Synthesis of (R)α-Cuparenone, (S)-Cuparene and Formal Synthesis of (R)-βCuparenone through Meinwald Rearrangement and Ring Closing Metathesis (RCM) Reaction. Tetrahedron 2017, 73, 809-818. (e) Vital, P.; Tanner, D. Efficient and Highly Enantioselective Formation of the All-Carbon Quaternary Stereocentre of Lyngbyatoxin A. Org. Biomol. Chem. 2006, 4, 4292-4298. (f) Simaan, M.; Delaye, P.-O.; Shi, M.; Marek, I. Cyclopropene Derivatives as Precursors to Enantioenriched Cyclopropanols andn-Butenals Possessing Quaternary Carbon Stereocenters. Angew. Chem. Int. Ed. 2015, 54, 12345-12348. (5) For selected direct strategies, see: (a) Haraguchi, R.; Kusakabe, A.; Mizutani, N.; Fukuzawa, S.-i. Transition-Metal-Free Formylation of Allylzinc Reagents Leading to α-Quaternary Aldehydes. Org. Lett. 2018, 20, 1613-1616. (b) Hojoh, K.; Ohmiya, H.; Sawamura, M. Synthesis of α-Quaternary Formimides and Aldehydes through Umpolung Asymmetric Copper Catalysis with Isocyanides. J. Am. Chem. Soc. 2017, 139, 2184-2187. (6) For selected reviews, see: (a) Guo, W.; Gomez, J. E.; Cristofol, A.; Xie, J.; Kleij, A. W. Catalytic Transformations of Functional Cyclic Organic Carbonates: Quo Vadis? Angew. Chem. Int. Ed. 2018, 57, 13735-13747. (b) Zhang, H.; Liu, H.-B.; Yue, J.-M. Organic Carbonates from Natural Sources. Chem. Rev. 2013, 114, 883-898. (7) (a) 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. (b) Khan, A.; Xing, J. X.; Zhao, J. M.; Kan, Y. H.; Zhang, W. B.; Zhang, Y. J. Palladium-Catalyzed Enantioselective Decarboxylative Cycloaddition of Vinylethylene Carbonates with Isocyanates. Chem. Eur. J. 2015, 21, 120-124. (c) 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. (d) 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. (e) 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. (f) Zhang, Y.; Khan, A. Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Electrophiles: Construction of Quaternary Stereocenters. Synlett 2015, 26, 853-860. (8) (a) 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. (b) Gómez, J. E.; Guo, W.; Kleij, A. W. Palladium-Catalyzed Stereoselective Formation of Substituted Allylic Thioethers and Sulfones. Org. Lett. 2016, 18, 6042-6045. (c) 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, 3981-3987. (d) Guo, W.; Martínez-Rodríguez, L.; Kuniyil, R.; Martin, E.; Escudero-Adán, E. C.; Maseras, F.; Kleij, A. W. Stereoselective and Versatile Preparation of Tri- and Tetrasubstituted Allylic Amine Scaffolds under Mild Conditions. J. Am. Chem. Soc. 2016, 138, 11970-11978. (e) Guo, W.; Martínez-Rodríguez, 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. (f) Miralles, N.; Gómez, J. E.; Kleij, A. W.; Fernández, E. Copper-Mediated SN2′ Allyl–Alkyl and Allyl–Boryl Couplings of Vinyl Cyclic Carbonates. Org. Lett. 2017, 19, 6096-6099. (g) 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. (9) (a) 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 BenzofuranFused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and
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Rearrangement via Transannular Bond Formation. J. Am. Chem. Soc. 2017, 139, 15304-15307. (b) Yang, L.-C.; Rong, Z.-Q.; Wang, Y.-N.; Tan, Z. Y.; Wang, M.; Zhao, Y. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition. Angew. Chem. Int. Ed. 2017, 56, 2927-2931. (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. (10) Singha, S.; Patra, T.; Daniliuc, C. G.; Glorius, F. Highly Enantioselective [5+2] Annulations through Cooperative NHeterocyclic Carbene (NHC) Organocatalysis and Palladium Catalysis. J. Am. Chem. Soc. 2018, 140, 3551-3554. (11) (a) Das, P.; Gondo, S.; Nagender, P.; Uno, H.; Tokunaga, E.; Shibata, N. Access to Benzo-fused Nine-membered Heterocyclic Alkenes with a Trifluoromethyl Carbinol Moiety via a double decarboxylative formal ring-expansion process under palladium catalysis. Chem. Sci. 2018, 9, 3276-3281. (b) 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,OContaining Eight-Membered Heterocycles. Adv. Synth. Catal. 2018, 360, 652-658. (c) 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 3,4-Dihydrooxepin-2(7H)-ones. Chem. Commun. 2018, 54, 9178-9181. (12) Trost, B. M.; Tometzki, G. B. Umpolung of Pi-Allylpalladium Intermediates - a Chemoselective Reductive Elimination of Diols. J. Org. Chem. 1988, 53, 915-917. (13) For selected reviews, see: (a) Rodríguez, N.; Goossen, L. J. Decarboxylative Coupling Reactions: a Modern Strategy for C–CBond Formation. Chem. Soc. Rev. 2011, 40, 5030. (b) Weaver, J. D.; Recio, A.; Grenning, A. J.; Tunge, J. A. Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions. Chem. Rev. 2011, 111, 1846-1913. (c) Xuan, J.; Zhang, Z.-G.; Xiao, W.-J. VisibleLight-Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives. Angew. Chem. Int. Ed. 2015, 54, 15632-15641. (14) (a) Duan, S.; Cheng, B.; Duan, X.; Bao, B.; Li, Y.; Zhai, H. Synthesis of cis-5,5a,6,10b-Tetrahydroindeno[2,1-b]indoles through Palladium-Catalyzed Decarboxylative Coupling of Vinyl Benzoxazinanones with Arynes. Org. Lett. 2018, 20, 1417-1420. (b) Wang, S.; Chen, X.; Ao, Q.; Wang, H.; Zhai, H. Decarboxylative Csp3–Csp3 Coupling for Benzylation of Unstable Ketone Enolates:
Synthesis of p-(Acylethyl)phenols. Chem. Commun. 2016, 52, 94549457. (c) Wang, S.; Liu, M.; Chen, X.; Wang, H.; Zhai, H. Coppercatalyzed Decarboxylative Propargylation/Hydroamination Reactions: Access to C3 β-Ketoester-Functionalized Indoles. Chem. Commun. 2018, 54, 8375-8378. (15) For selected examples, see: (a) Werner, E. W.; Mei, T. S.; Burckle, A. J.; Sigman, M. S. Enantioselective Heck Arylations of Acyclic Alkenyl Alcohols Using a Redox-Relay Strategy. Science 2012, 338, 1455-1458. (b) Xu, L.; Hilton, M. J.; Zhang, X.; Norrby, P.-O.; Wu, Y.-D.; Sigman, M. S.; Wiest, O. Mechanism, Reactivity, and Selectivity in Palladium-Catalyzed Redox-Relay Heck Arylations of Alkenyl Alcohols. J. Am. Chem. Soc. 2014, 136, 1960-1967. (16) Delcamp, J. H.; White, M. C. Sequential Hydrocarbon Functionalization: Allylic C−H Oxidation/Vinylic C−H Arylation. J. Am. Chem. Soc. 2006, 128, 15076-15077. (17) For more details of screening of the ratio of Pd(tBu3)2/DPEPhos, see the Supporting Information. (18) Considering that hundreds of sulfur-containing drugs have been approved by FDA and sulfur functional groups exist widely in pharmaceuticals and natural products, we chose the sulfur-containing VEC 1h to explore the scope of allylic acetates. When VEC 1a, without substitution on the aromatic ring, was explored with acetate 2a’ under the same conditions, the desired product was obtained in 49% yield. (19) The linear aryl-substituted allylic acetate, cinnamyl acetate has been explored with VEC 1h under the same condition, giving the product 7a in a slightly reduced yield (46%). (20) Yamada, S.; Morizono, D.; Yamamoto, K. Mild Oxidation of Aldehydes to the Corresponding Carboxylic-Acids and Esters Alkaline Iodine Oxidation Revisited. Tetrahedron Lett 1992, 33, 43294332. (21) The crystal structure of hydrazone 8c was deposited at the Cambridge Crystallographic Data Centre (tracking number: 1862065). (22) The 31P NMR experiments demonstrated that the bidentate phosphine (DPEPhos) might replace the alkyl phosphines (tBu3P) to form the diphosphine palladium complex. For more details, see the Supporting Information.
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Insert Table of Contents artwork here O O O
+
R
VECs
L
"Pd"
Pd
O CO2
E+
-
O
R
nucleophile
high chemoselectivity
umpolung
AcO
R
electrophile
R CHO
dienolate
high functional diversity
all-carbon quaternary center
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