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Enantioselective Synthesis of Axially Chiral Biaryls via CuCatalyzed Acyloxylation of Cyclic Diaryliodonium Salts Kai Zhu, Kai Xu, Qi Fang, Yi Wang, Bencan Tang, and Fengzhi Zhang ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00695 • Publication Date (Web): 22 Apr 2019 Downloaded from http://pubs.acs.org on April 22, 2019
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ACS Catalysis
Enantioselective Synthesis of Axially Chiral Biaryls via CuCatalyzed Acyloxylation of Cyclic Diaryliodonium Salts Kai Zhu, †, ‡ Kai Xu, † Qi Fang, † Yi Wang, † Bencan Tang§ and Fengzhi Zhang*, †, ‡ College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, P. R. China Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, P. R. China §Department of Chemical and Environment Engineering, The University of Nottingham Ningbo China, Ningbo, 315100
†
‡
ABSTRACT: We report here a Cu-catalyzed enantioselective acyloxylation of cyclic diaryliodonium salts. With readily available cyclic diaryliodonium salts and ubiquitous aliphatic or (hetero)aromatic carboxylic acids as the starting materials, various axially chiral acyloxylated 2-iodobiaryls were prepared in R1 R2 enantioselective excellent yields and enantioselectivity (mostly 99% acyloxylation I R1 yield and 99% ee). DFT calculations were conducted CO2H + O R2 to reveal the stereo- and regioselectivity. This simple > 40 examples I mostly 99% yield reaction protocol can be employed for the late stage O OTf modification of some drug molecules. Finally, by Readily available carboxylic acids and 99% ee Valuable f unctionalized diversity-oriented transformations these acyloxylated and cyclic diaryliodonium salts axially chiral biaryls 2-iodobiaryl products can be easily transformed into diverse valuable functionalized biaryls which could be used as chiral ligands or functional materials. KEYWORDS: diaryliodonium salts, axially chiral biaryl, copper catalysis, acyloxylation, diversity oriented synthesis
Atropisomerism, a dynamic type of axial chirality arising from a large degree of hindrance to rotation about a bond, exists in many common scaffolds including biaryls, benzamides, anilides, diaryl ethers and diaryl amines.1 In drug discovery, the prevalence of atropisomerism has been increasing over the last decade.2 It has become increasingly appreciated that each possible atropisomeric conformation of a molecule can possess different drug properties and target profiles.3 Several research groups have demonstrated that the selectivity of a promiscuous compound can be improved by rigidifying it into the relevant conformation for the desired binding target.4 As atropisomerism becomes more prevalent, it’s highly important to develop novel and improved methods to obtain enantiopure atropisomers. Biaryl atropisomerism is the most typical type of axial chirality arising from a large degree of hindrance to rotation about the aryl-aryl single bond, which is ubiquitous in pharmaceuticals (such as vancomycin5 used as antibiotic), bioactive natural product (such as gossypol6 used as Bcl-2 inhibitor), functional materials (such as the dopants7 used in nematic liquid crystals) and chiral ligands8 (Figure 1). O OH OH
HO
H2N O HO O Me MeO O Cl O O HO O HOOC
O NH
N H
Cl H N
O O
N H O
H N O
NH2 HO
OH OH
vancomycin antibiotic
OH HO N H
OH
O
OH
O
chiral ligand NH
O HO HO
R
R O dopant in liquid crystals H
OH
OH
OH OH H O gossypol Bcl-2 inhibitor
Figure 1: Representative molecules containing axially chiral biaryl skeleton
Although several strategies including metal-catalyzed and organo-catalytic processes have been developed for the construction of biaryl atropisomers, 1,9,10 there are still some challenges need to be addressed. First, how to make the reaction happen in excellent yield and full enantiocontrol under mild conditions with low catalyst loading; Second, how to control the regioselectivity in the presence of other reaction sites; Third, how to increase the functional group tolerance and the structural diversity of the axially chiral biaryls. Recently we completed the copper-catalyzed acyloxylation of cyclic diaryliodonium salts for the construction of racemic biaryls.11 We envisioned that the above challenges might be addressed by developing our enantioselective version of acyloxylation for the access of axially chiral biaryls. Compared to the linear diaryliodonium salts which have been widely employed as the arylating reagents in (non)asymmetric reactions,12,13 the research especially the asymmetric synthesis involved with the cyclic diaryliodonium salts are very rare.14,15 In 2004, the Hayashi group reported the palladium-catalyzed Heck and carbonylation reactions of cyclic diaryliodonium salt, which opened a new window for the access of enantiopure biaryl atropisomers although only one asymmetric example reported with 38% yield and 28% ee (Scheme 1a).16 During our investigation, the Gu group reported excellent examples about the enantioselective amination and thiolative of cyclic diaryliodonum salts for the access of axially chiral biaryls (Scheme 1b).17 In addition, the Gu group also reported an asymmetric ring-opening reaction of diaryliodoniums to access molecules with center chirality.18 In continuation of our interest in the diaryliodonium salt chemistry,19 herein we report our enantioselective acyloxylation of cyclic diaryliodonium salts for the efficient preparation of axially chiral biaryls under economical, mild and scalable conditions (Scheme 1c), and demonstrate that they can be served as platform molecules for the divergent synthesis of various valuable chiral ligands or building blocks.
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(a) Hayash's Pd-catalyzed asymmetric carboxylation Pd(OAc)2
MeOH + CO +
I CO2Me
(R)-BINAP Et3N, DMF
I
OTf 38% yield, 28% ee (b) Gu's Cu-catalyzed asymmetric amination and thiolation R1 R2 R X
+ I Y Y = OTf or PF6
X = NH2/COSK
Cu(PyBox)2PF6 I R1 2 Z or Cu(CH3CN)4PF6, R (S)-(Ph)-Box up to 99% yield Z = NHR/SCOR and 99% ee
(c) This work: Cu-catalyzed asymmetric acyloxylation R1 R2
Cu(OAc)2 chiral Box ligand
I R1 O R2 > 40 examples I mostly 99% yield O OTf and 99% ee Readily available carboxylic acids Valuable f unctionalized and cyclic diaryliodonium salts axially chiral biaryls CO2H
+
Scheme 1: Asymmetric diaryliodonium salts.
synthesis
with
cyclic
We started our investigation by reacting benzoic acid 1a with cyclic diaryliodonium salt 2a in DCM at 30 oC with Cu(OAc)2 (10 mol%) as the catalyst (Table 1). Table 1: Optimization of the reaction conditions COOH
Cu(OAc)2
+
I
1a
Ph P
O
O
Ph P Ph
O Ph
L4
N
Entrya 1 2 3 4 5 6 7 8 9 10 11 12 aReaction
L7
Cat/mol% 10 10 10 10 10 10 10 10 10 10 5 5
O
3a, 99%, 99% ee
F
I O
O
O N
O
O
Cl
I O O
O
3b, 99%, 99% ee
Ph
Ligand/mol% L1/20 L2/20 L3/20 L4/20 L5/20 L6/20 L7/20 L8/20 L9/20 L10/20 L8/10 L8/5
L9
Br
I O
O
O N N
N N L8
R O
3c, 98%, 99% ee
3d, 99%, 99% ee
I O
I O
L6 O
Bn
3
Ph
L5
I O
L8 (5 mol%), Na2CO3 (3 eq.) DCM, 30 oC, 12 h
I O
I O
N N
N
N Bn
O
O
N N
O
I 2a OTf (0.12 mmol)
N
N
O O
1 (0.1 mmol)
L3
N N
N
+
N
L2
O
N N
Cu(OAc)2 (5 mol%) R COOH
O
O
Ph
L1
With the optimal conditions in hands, we first examined the scope of carboxylic acids for this enantioselective acyloxylation reaction (Table 2).
O 3a
2a
O P N O
We laid special stress on screening the effects of various chiral ligands. First, the chiral phosphoramidite L1 and phosphine L2 were tested which gave either no or very poor enantioselectivity, albeit virtually quantitative yields of the desired product 3a were obtained (Table 1, entries 1 and 2). The pyridine oxazoline ligands L2-7 were then screened. The reaction using pyridine oxazoline ligand L3 gave only 3% ee (Table 1, entry 3). The C2-symmetric pyridine bis(oxazoline) ligands (PyBOX) L4-7 led to 66-70% ee (Table 1, entries 4-6). Finally, the bis(oxazoline) ligands (BOX) L8-10 with an isopropyl linker were screened. To our pleasant surprise, it was found the ee was increased dramatically to 99% in almost quantitative yield when L8 was used (Table 1, entry 8). The reaction with phenyl-substituted ligand L9 was almost equally effective (Table 1, entry 9). However, the ee was decreased to 67% when the tert-butyl-substitued bisoxazoline L10 was used (Table 1, entry 10). Further investigation with L8 identified that the loading of catalyst and ligand could be reduced to 5 mol% without compromising the yield or enantioselectivity of 3a (Table 1, entries 11-12). The control experiment showed that no reaction happened in the absence of copper catalyst (not shown here).
Table 2: Substrate scope of carboxylic acids
I O
chiral ligand Na2CO3, DCM
OTf
Page 2 of 8
O OMe
I O
O
Ph
Yieldb 99 99 99 99 93 99 90 99 99 98 99 99
eec 0 8 3 66 64 67 70 99 97 67 99 99
conditions: benzoic acid 1a (0.1 mmol), iodonium salt 2a (0.12 mmol), Cu(OAc)2 (x mol%), chiral ligand (x mol%), Na2CO3 (0.3 mmol), DCM (2.0 mL), 30 oC, 12 h. b Isolated yields. cDetermined by chiral HPLC.
O
O
3e, 98%, 99% ee
L10
I O
3f, 99%, 99% ee
NO2
O
I O
I O
O
O 3u, 94%, 99% ee
3r, 99%, 99% ee
I O 3v, 82%, 99% ee
I O
3t, 95%, 99% ee
Br O
3w, 89%, 99% ee
Ph O
3s, 91%, 95% ee
Cl O
I O O
O
Ph
O 3p, 98%, 98% ee
I O
I O
3q, 91%, 99% ee
I O
3o, 98%, 99% ee
3n, N.R.
O
O
I O
N
O
3l, 95%, 99% ee
3k, 98%, 99% ee
O
I O
I O
I O O
O
O
3h, 98%, 97% ee
I O
3j, 98%, 99% ee
3m, 94%, 99% ee
O
3g, 99%, 95% ee
I O
3i, 98%, 99% ee
S
OH
H
I O
NHCbz O
3x, 97%, 98% ee
Generally the benzoic acid derivatives with either simple alkyl (3b), halogen (3c-e), strong electron-donating (3f and 3g)
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or withdrawing (3h and 3i) substituents all gave excellent yields and ee (>98% yield, >95% ee). 1-Naphthoic acid (3j) and 2-naphthoic acid (3k) also proceed steadily to give perfect stereo induction. The reactions with heteroaromatic carboxylic acids such as 2-furoic acid (3l) and 2-thiophenecarboxylic acid (3m) afforded the corresponding products in excellent yields and ee. However, 2-quinolinecarboxylic acid (3n) was negative for this reaction probably because of the strong coordinate effect of nitrogen. Alkyl carboxylic acids also worked smoothly and delivered the corresponding products in excellent yields and ee (3o-x) except the one with chlorine substituent (3v) giving a slightly decreased yield. Lots of functional groups such as hydroxyl, formyl, nitro, alkynyl, alkenyl, halogen and amide were tolerated under these mild conditions, which provide functional handles for further transformations. It is worth mentioning that the reaction, with carboxylic acids bearing with hydroxyl or unsaturated functional groups as substrates, took place regioselectively on the carboxylic acid position without touching either hydroxyl (3g), alkynyl (3r) or alkenyl (3s) groups which are normally reactive in the copper catalyzed reactions involved with linear diaryliodonium salts.20
carboxylic acid attacking from the less hindered side of the diaryliodonium salts. Again, all kinds of functional groups such as halide, nitro, ester or even the hydroxyl group are tolerated under this mild reaction conditions. To gain more understanding of this reaction, we further conducted the following competition experiments (Scheme 2). First, the reactivity of the linear 5 and cyclic diaryliodonium salt 2a was compared (Scheme 2, equation 1). Treatment of the benzoic acid 1a with the same amount of 5 and 2a under the optimized conditions, only the axially chiral product 3a was obtained in 85% yield, which demonstrated the cyclic diaryliodonium salt 2a is much more reactive than the linear one 5 under these conditions. We then examined the electronic effect of the substituents on the carboxylic acids (Scheme 2, equation 2). The reaction with a mixture of 1i, 1f and 2a gave the product 3h as the major product which showed the electron deficient carboxylic acid reacts much faster than the electron rich one. It gave almost equal amount of products 3a and 3p by reacting the mixture of acids 1a and 1p with 2a (Scheme 2, equation 3).
Next, we examined the scope of substituted cyclic diaryliodoniums salts (Table 3). First, the symmetric cyclic diaryliodonium salts were tested (4a-e). When additional methyl substituents were introduced to the meta- or paraposition of the C-I bond, the reactions gave the corresponding products in almost quantitative yields and ee at 0 0C (4a-d). The reaction of dinaphthaleneiodonium salt gave the product 4e in 99% ee and an un-optimized moderate yield. The nonsymmetric cyclic diaryliodonium salts were then examined (4f-p). It was found that all of them with either a methyl, fluorine or chlorine atom at the adjacent position of the C-I bond delivered the axially chiral products efficiently (>93% yield, >97% ee), which took place regioselectively with the Table 3: Substrate scope of cyclic diaryliodonium salts
I
R1 R2 R COOH
+ 2 OTf (0.12 mmol)
I O
I O
Ph O
I O
4b,[a] 99%, 99% ee I O
Ph O
F
I O
O
O
I O
I O
Ph O
4m, 98%, 99% ee
Ph O
4n, 96%, 99% ee
O O
I O
1p 0.2 mmol
4o, 93%, 99% ee
I
O
OTf 2a 0.2 mmol
3f, 16%
I O
+ O
3a, 46%
(3)
I O O 3p, 44%
Scheme 2: Competition experiments The single crystal X-ray diffraction analysis of 4j was then performed to determine the stereoselectivity of this reaction.21 The stereochemistry of 4j was determined to be R configuration. In terms of the regioselectivity, surprisingly it was found that the acid 1j only attacked the salt 2 from the phenyl ring without fluorine (Figure 2).
NO2
I O
4j
Figure 2: X-ray structure of 4j
O
I O
O
3h, 69%
conditions
OMe (2)
I O
+
optimized
+
4l, 95%, 99% ee
HO O
conditions
2a 0.2 mmol
COOH
I O
Ph
4k, 97%, 99% ee
OTf
I O
O
O 4h, 98%, 99% ee
O
4j, 99%, 99% ee
1a 0.2 mmol
I
1f 0.2 mmol +
COOH
3a, 85% NO2
optimized
COOH
1i 0.2 mmol
(1) O
2a 0.2 mmol
+
Cl
I O O
4i, 96%, 99% ee
COOH
I O
conditions OTf
OMe
F
4d,[a] 99%, 99% ee F
Cl
I O
Ph
NO2
optimized +
5 0.2 mmol
I O
4g,99%, 99% ee
NO2
COOH 1a 0.2 mmol
OTf
I O
I O
Ph
R
O
4c,[a] 99%, 99% ee
4f, 99%, 99% ee
F
I O 4O
Ph
O
4e, 52%, 99% ee
R1 R2
O
O
4a,[a] 99%, 99% ee
a
L8 (5 mol%), Na2CO3 (3 eq.) DCM, 30 oC, 12 h
I
1 (0.1 mmol)
I O
Cu(OAc)2 (5 mol%)
I
+
+
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
ACS Catalysis
Ph O
4p, 96%, 97% ee
Reaction temperature: 0 oC,
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Figure 3: DFT-calculated free-energy profile (kcal/mol) for Cu-catalyzed acyloxylation of cyclic diaryliodonium salt. All hydrogen atoms in transition-state geometries are not shown for clarity. Key distances are indicated in Å. Figures of the transition-state geometries were prepared using CYLview. To reveal the possible reaction mechanism and the origin of To further demonstrate the utility of these axially chiral enantio-/regioselectivity, the DFT calculations were acyloxylated products, the gram-scale reaction was conducted, conducted.22 The possible reaction pathway might involve and the platform molecule 3a (1.7 g, 99% yield and 99% ee) three steps (Figure 3): a Cu-catalyzed ring-opening step of the was prepared efficiently with further reduced amounts of cyclic diaryliodonium salt, an exergonic reorientation of the copper catalyst and chiral ligand (1 mol%). Compound 3a was carboxyl group, and the final acyloxylation that generates the then converted into various valuable functionalized biaryls by desired product. The pathway leading to the major (R)diversity-oriented transformations (Scheme 4). The enantiomer has an overall barrier of 9.7 kcal/mol, which is 5.3 alkenylated biaryl 11 was prepared in 71% yield and 99% ee kcal/mol lower in energy than that of minor (S)-enantiomer under the Heck coupling conditions with styrene. By cross (see SI, Figure S1). The high barrier for TS1-S is probably coupling with pyridine-3-boronic acid or diphenylphosphine caused by the steric repulsion between the indeno group in the the chiral bidentate pyridine (12) and phosphino ligands (13) ligand and the cyclic diaryliodonium salt (See SI, Figure S2). could be prepared in good yields and excellent ee respectively. In terms of the regioselectivity, DFT calculations show the Functional groups such as phenyl could be introduced to give bond cleavage between iodine and phenyl ring is preferred 14 efficiently by a Pd-catalyzed C-H activation/arylation with over the one between iodine and fluorine-substituted phenyl the ester as the directing group. Finally, the ester 3a could be ring by 4.9 kcal/mol in energy (See SI, Figure S3), explaining hydrolyzed to give the monophenol 15 and then biphenol 16 in why only one single product 4j was obtained. excellent yields and enantioselectivities. Treated biphenol 16 with phosphoryl chloride afforded the axially chiral Given that the carboxylic acid motifs are present in a range phosphoric acid 17 which is a highly valuable chiral ligand of small-molecule drugs or pre-clinical candidates, the lateand might be difficult to access by other methods.8,24 stage functionalization of such molecules would be a powerful demonstration of the utility of this process. To confirm this strategy, we selected five of most prescribed drugs I PPh2 (Indometacin, febuxostat, furosemide, diclofenac and N OH OH OH naproxen) and treated them to the reaction conditions (Scheme 3). Each of these drug molecules underwent smooth reaction 12, 80%, 95% ee 13, 52%, 99% ee 15, 98%, 99% ee with the cyclic diaryliodonium salt 2a and furnished the e b c f desired drug-like products 6-10 respectively in excellent enantioselectivities with an axially chiral biaryl moiety, which Ph OH might have different bioavailability and target profiles.23 I Ph
O
OMe
O
I O
N
O O HN
8 (from furosemide) 88%, 99% ee
O
S
7 (from febuxostat) 98%, 99% ee
I O
Cl I O
O
d
HN Cl O
O
9 (from diclofenac) 99%, 99% ee
10 (from naproxen) 99%, dr 99:1
Scheme 3: Late stage modification of drug molecules
O
aStyrene,
16, 84%, 99% ee g O
Ph
O Ph 14, 73%, 99% ee
I O
OH
Ph
O 3a
11, 71%, 99% ee
O
Cl
O 6 (from indometacin) 80%, 99% ee NH2 O S O Cl
CN
N
I O
I O
a
O
O
O P OH
17, 85%
Pd(OAc)2, AgOAc, AcOH, 110 oC; bPyridine-3boronic acid, Pd(PPh3)4, K2CO3, DMF, 110 oC; c Diphenylphosphine, CuI, Cs2CO3, toluene, 100 oC; dPh2IOTf, Pd(OAc)2, Ac2O, TfOH, DCE, 50 oC; eLiOH, THF/MeOH/H2O, 40 oC; fCu(OAc)2.H2O, D-glucose, KOH,
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ACS Catalysis DMSO/H2O, 110 oC; g1. POCl3, TEA, DCM, 45 oC; 2. THF/H2O, 60 oC. Scheme 4: Diversity oriented transformations of product 3a. In summary, we have developed an efficient protocol for the construction of axially chiral biaryls via copper-catalyzed acyloxylation of cyclic diaryliodonium salts with commercially available carboxylic acids. Various functionalized biaryl acetates were prepared in excellent yields and enantioselectivity, and a wide range of functional groups are tolerated under the mild and scalable reaction conditions. DFT calculations were conducted to reveal the stereo- and regioselectivity of this reaction. This simple reaction protocol can be applied for the late stage modification of some drug molecules to give the novel drug-like atropisomers. Finally, we further demonstrated that various valuable axially chiral biaryl ligands or functional molecules can be accessed efficiently by diversity-oriented transformations of the biaryl acetate products. We expect this highly efficient atropisomer conformation controlling work will become a more prevalent strategy in asymmetric synthesis and drug discovery.
■ ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI:
■ AUTHOR INFORMATION Corresponding Author *E-mail:
[email protected] ORCID Fengzhi Zhang: 0000-0001-9542-6634 Notes The authors declare no competing financial interest.
■ ACKNOWLEDGMENT This research was supported by the NSFC under grant No. 21871234, and Zhejiang Provincial NSFC for Distinguished Young Scholars under grant No. LR15H300001. We appreciate the help from Prof. Guilin Zhuang of Zhejiang University of Technology for X-ray analysis.
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Atropisomers via Peptide-Catalyzed Asymmetric Bromination. Science. 2010, 328, 1251-1255. (b) De, C. K.; Pesciaioli, F.; List, B. Catalytic Asymmetric Benzidine Rearrangement. Angew. Chem., Int. Ed. 2013, 52, 9293-9295. (c) Li, G. Q.; Gao, H. Y.; Keene, C.; Devonas, M.; Ess, D. H.; Kürti, L. Organocatalytic Aryl-Aryl Bond Formation: An Atroposelective [3,3]-Rearrangement Approach to BINAM Derivatives. J. Am. Chem. Soc. 2013, 135, 7414-7417. (d) Mori, K.; Ichikawa, Y.; Kobayashi, M.; Shibata, Y.; Yamanaka, M.; Akiyama, T. Enantioselective Synthesis of Multisubstituted Biaryl Skeleton by Chiral Phosphoric Acid Catalyzed Desymmetrization/Kinetic Resolution Sequence. J. Am. Chem. Soc. 2013, 135, 3964-3970. (e) Cheng, D. J.; Yan, L.; Tian, S. K.; Wu, M. Y.; Wang, L. X.; Fan, Z. L.; Zheng, S. C.; Liu, X. Y.; Tan, B. Highly Enantioselective Kinetic Resolution of Axially Chiral BINAM Derivatives Catalyzed by a Brønsted Acid. Angew. Chem., Int. Ed. 2014, 53, 3684-3687. (f) Yu, C. G.; Huang, H.; Li, X. M.; Zhang, Y. T.; Wang, W. Dynamic Kinetic Resolution of Biaryl Lactones via a Chiral Bifunctional Amine Thiourea-Catalyzed Highly Atropoenantioselective Transesterification. J. Am. Chem. Soc. 2016, 138, 6956-6959. (g) Zheng, S. C.; Wu, S.; Zhou, Q. H.; Chung, L. W.; Ye, L.; Tan, B. Organocatalytic Atroposelective Synthesis of Axially Chiral Styrenes. Nat. Commun. 2017, 8, 15238. (h) Zhang, H. H.; Wang, C. S.; Li, C.; Mei, G. J.; Li, Y.; Shi, F. Design and Enantioselective Construction of Axially Chiral Naphthyl-Indole Skeletons. Angew. Chem., Int. Ed. 2017, 56, 116-121. (i) Zhang, J.; Wang, J. Atropoenantioselective Redox-Neutral Amination of Biaryl Compounds through Borrowing Hydrogen and Dynamic Kinetic Resolution. Angew. Chem., Int. Ed. 2018, 57, 465-469. (11) (a) Xie, H.; Yang, S.; Zhang, C. X.; Ding, M. R.; Liu, M.; Guo, J.; Zhang, F. Z. Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic Diaryliodonium Salts. J. Org. Chem. 2017, 82, 5250-5262. (b) Xie, H.; Ding, M. R.; Liu, M.; Hu. T,; Zhang, F. Z. Synthesis of Functionalized Biaryls and Poly (hetero) aryl Containing Medium-Sized Lactones with Cyclic Diaryliodonium Salts. Org. Lett. 2017, 19，2600-2603. (12) For reviews about linear diaryliodonium salts: (a) Merritt, E. A.; Olofsson, B. Diaryliodonium Salts: A Journey from Obscurity to Fame. Angew. Chem., Int. Ed. 2009, 48, 9052-9070. (b) Grushin, V. V. Cyclic Diaryliodonium Ions: Old Mysteries Solved and New Applications Envisaged. Chem. Soc. Rev. 2000, 29, 315-324. (c) Yoshimura, A.; Zhdankin, V. V. Advances in Synthetic Applications of Hypervalent Iodine Compounds. Chem. Rev. 2016, 116, 3328-3435. (13) Selected recent examples about linear diaryliodonium salts: (a) Bigot, A.; Williamson, A. E.; Gaunt, M. J. Enantioselective αarylation of N-acyloxazolidinones with Copper(II)-Bisoxazoline Catalysts and Diaryliodonium Salts. J. Am. Chem. Soc. 2017, 133, 13778-13781. (b) Lukamto, D. H.; Gaunt, M. J. Enantioselective Copper-Catalyzed Arylation-Driven Semipinacol Rearrangement of Tertiary Allylic Alcohols with Diaryliodonium Salts. J. Am. Chem. Soc. 2017, 139, 9160-9163. (c) Teskey, C.; Sohel, S. M. A.; Bunting, D. L.; Modha, S. G.; Greaney, M. F. Domino N-/C-Arylation via In Situ Generation of a Directing Group: Atom-Efficient Arylation Using Diaryliodonium Salts. Angew. Chem., Int. Ed. 2017, 56, 52635266. (d) Reitti, M.; Gurubrahamam, R.; Walther, M.; Lindstedt, E.; Olofsson, B. Synthesis of Phenols and Aryl Silyl Ethers via Arylation of Complementary Hydroxide Surrogates. Org. Lett. 2018, 20, 17851788. (e) Beaud, R.; Phipps, R. J.; Gaunt, M. J. Enantioselective CuCatalyzed Arylation of Secondary Phosphine Oxides with Diaryliodonium Salts toward the Synthesis of P-Chiral Phosphines. J. Am. Chem. Soc. 2016, 138, 13183-13186. (f) Ye, B.; Zhao, J.; Zhao, K.; McKenna, J. M.; Toste, F. D. Chiral Diaryliodonium Phosphate Enables Light Driven Diastereoselective α-C(sp3)-H Acetalization. J. Am. Chem. Soc. 2018, 140, 8350-8356. (g) Wu, H.; Wang, Q.; Zhu, J. Copper-Catalyzed Enantioselective Arylative Desymmetrization of Prochiral Cyclopentenes with Diaryliodonium Salts. Angew. Chem., Int. Ed. 2018, 57, 2721-2725. (h) Chen, H.; Han, J.; Wang, L. Intramolecular Aryl Migration of Diaryliodonium Salts: Access to ortho-Iodo Diaryl Ethers. Angew. Chem., Int. Ed. 2018, 57, 1231312317.
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(14) For reviews about cyclic diaryliodonium salts, see: (a) Chatterjee, N.; Goswami, A. Synthesis and Application of Cyclic Diaryliodonium Salts: A Platform for Bifunctionalization in a Single Step. Eur. J. Org. Chem. 2017, 3023-3032. (b) Wang, M.; Chen, S. H.; Jiang, X. F. Atom-Economical Applications of Diaryliodonium Salts. Chem. Asian J. 2018, 13, 2195-2207. (15) Selected recent methods for the racemic ring opening of cyclic diaryliodonium salts: (a) Zhu, D.; Wu, Z.; Luo, B.; Du. Y.; Liu, P.; Chen, Y.; Hu, Y.; Huang, P.; Wen, S. Heterocyclic Iodoniums for the Assembly of Oxygen-Bridged Polycyclic Heteroarenes with Water as the Oxygen Source. Org. Lett. 2018, 20, 4815-4818. (b) Wang, M.; Fan, Q.; Jiang, X. Nitrogen-Iodine Exchange of Diaryliodonium Salts: Access to Acridine and Carbazole. Org. Lett. 2018, 20, 216-219. (c) Mathew, B. P.; Yang, H. J.; Kim, J.; Lee, B. J.; Kim, Y. T.; Lee, S.; Lee, C. Y.; Choe, W.; Myung, K.; Park, J. U.; Hong, S. Y. An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C-H Bond Activations. Angew. Chem., Int. Ed. 2017, 56, 5007-5011. (16) (a) Kina, A.; Miki, H.; Cho, Y. H.; Hayashi, T. PalladiumCatalyzed Heck and Carbonylation Reactions of a Dinaphthaleneiodonium Salt Forming Functionalized 2-Iodo-1,1’Binaphthyls. Adv. Synth. Catal. 2004, 346, 1728-1732. (b) Shimada, T.; Cho, Y. H.; Hayashi, T. Nickel-Catalyzed Asymmetric Grignard Cross-Coupling of Dinaphthothiophene Giving Axially Chiral 1.1’Binaphthyls. J. Am. Chem. Soc. 2002, 124, 13396-13397. (17) During our preparation of this manuscript, examples about the enantioselective amination and thiolative of cyclic diaryliodonium salts were reported by Gu group: (a) Zhao, K.; Duan, L. H.; Xu, S. B.; Jiang, J. L.; Fu, Y.; Gu, Z. H. Enhanced Reactivity by Torsional Strain of Cyclic Diaryliodonium in Cu-Catalyzed Enantioselective Ring-Opening Reaction. Chem. 2018, 4, 599-612. (b) Hou, M. Q.; Deng, R. X.; Gu, Z. H. Cu-Catalyzed Enantioselective Atropisomer Synthesis via Thiolative Ring Opening of Five-Membered Cyclic Diaryliodoniums. Org. Lett. 2018, 20, 5779-5783. c) Xu, S. B.; Zhao, K.; Gu, Z. H. Copper-Catalyzed Asymmetric Ring-Opening of Cyclic Diaryliodonium with Benzylic and Aliphatic Amines. Adv. Synth. Catal. 2018, 360, 3877-3883. (18) Li, B.; Chao, Z. Y.; Li, C. Y.; Gu, Z. H. Cu-Catalyzed Enantioselective Ring Opening of Cyclic Diaryliodoniums toward the Synthesis of Chiral Diarylmethanes. J. Am. Chem. Soc. 2018, 140, 9400-9403. (19) (a) Zhang, F.; Das, S.; Walkinshaw, A. J.; Casitas, A.; Taylor, M.; Suero, M. G.; Gaunt, M. J. Cu-Catalyzed Cascades to Carbocycles: Union of Diaryliodonium Salts with Alkenes or Alkynes Exploiting Remote Carbocations. J. Am. Chem. Soc. 2014, 136, 8851-8854. (b) Yang, S.; Hua, W. K.; Wu, Y. Q.; Hu, T.; Wang, F.; Zhang, X.; Zhang, F. Z. Site-Selective Synthesis of Functionalized Dibenzo [f, h] Quinolines and Their Derivatives Involving Cyclic Diaryliodonium Salts via a Decarboxylative Annulation Strategy. Chem. Commun. 2018, 54, 3239-3242. (c) Yang, S.; Wang, F.; Wu, Y.; Hua, W. K.; Zhang, F. Z. Synthesis of Functionalized Triphenylenes via a Traceless Directing Group Strategy. Org. Lett. 2018, 20, 1491-1495. (20) (a) Phipps, R. J.; McMurray, L.; Ritter, S.; Duong, H. A.; Gaunt, M. J. Copper-Catalyzed Alkene Arylation with Diaryliodonium Salts. J. Am. Chem. Soc. 2012, 134, 10773-10776. (b) Suero, M. G.; Bayle, E. D.; Collins, B. S. L.; Gaunt, M. J. Copper-Catalyzed Electrophilic Carbofunctionalization of Alkynes to Highly Functionalized Tetrasubstituted Alkenes. J. Am. Chem. Soc. 2013, 135, 5332-5335. (21) CCDC 1888554 (4j) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre. (22) CYLview, 1.0b; Legault, C. Y., Université de Sherbrooke, 2009 (http://www.cylview.org). (23) (a) Mizoi, K.; Takahashi, M.; Haba, M.; Hosokawa, M. Synthesis and Evaluation of Atorvastatin Esters as Prodrugs Metabolically Activated by Human Carboxylesterases. Bioorg. Med. Chem. Lett. 2016, 26, 921-923. (b) Takahashi, M.; Ogawa, T.; Kashiwagi, H.; Fukushima, F.; Yoshitsugu, M. Chemical Synthesis of an
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ACS Catalysis Indomethacin Ester Prodrug and Its Metabolic Activation by Human Carboxylesterase 1. Bioorg. Med. Chem. Lett. 2018, 28, 997-1000. (24) (a) Tang, W.; Zhang, X. New Chiral Phosphorus Ligands for Enantioselective Hydrogenation. Chem. Rev. 2003, 103, 3029-3070. (b) Jiang, G.; Halder, R.; Fang, T.; List, B. A Highly Enantioselective
Overman Rearrangement through Asymmetric Counteranion-Directed Palladium Catalysis. Angew. Chem., Int. Ed. 2011, 50, 9752-9755. (c) Privileged Chiral Ligands and Catalysis. Zhou, Q. L., Ed.; WileyVCH, Weinheim, 2011, 295-332.
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Enantioselective Synthesis of Axially Chiral Biaryls via CuCatalyzed Acyloxylation of Cyclic Diaryliodonium Salts Kai Zhu, †, ‡ Kai Xu, † Qi Fang, † Yi Wang, † Bencan Tang§ and Fengzhi Zhang*, †, ‡ In the presence of catalytic amount of Cu(OAc)2 and chiral Box ligand, the reactions of (hetero)aromatic or aliphatic carboxylic acids with cyclic diaryliodonium salts afforded the valuable axially chiral biaryls in excellent yields and enantioselectivities.
R1 R2 CO2H
Cu(OAc)2, chiral Box ligand
+
R1 R2
I O
> 40 examples mostly 99% yield O OTf and 99% ee Readily available carboxylic acids Valuablef unctionalized and cyclic diaryliodonium salts axially chiral biaryls I
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