Subscriber access provided by University of South Dakota
Communication
Directed Copper-Catalyzed Intermolecular HeckType Reaction of Unactivated Olefins and Alkyl Halides Chunlin Tang, Ran Zhang, Bo Zhu, Junkai Fu, Yi Deng, Li Tian, Wei Guan, and Xihe Bi J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b10874 • Publication Date (Web): 13 Nov 2018 Downloaded from http://pubs.acs.org on November 13, 2018
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 7 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
Journal of the American Chemical Society
Directed Copper-Catalyzed Intermolecular Heck-Type Reaction of Unactivated Olefins and Alkyl Halides Chunlin Tang,†,# Ran Zhang,†,# Bo Zhu,†,# Junkai Fu*,†,‡, Yi Deng,† Li Tian,† Wei Guan*,† and Xihe Bi*,† †
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Department of Chemistry, Northeast Normal University, Changchun 130024, China ‡ Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China Supporting Information Placeholder ABSTRACT: A new type of intermolecular alkylative olefination of unactivated olefins and alkyl halides has been realized for the first time. This copper-promoted Heck-type reaction employs a directing-group strategy to efficiently produce the coupled alkyl olefin products with excellent regio- and stereoselectivity. A broad substrate scope including 1°, 2°, and 3°alkyl bromides and various non-activated alkenes could be well tolerated. DFT calculations disclosed a dimethyl sulfoxide assisted concerted H−Br elimination process of a conformationally strained Cu(III)cyclic transition state.
The Mizoroki−Heck reaction1 has developed into an essential advancement in constructing C−C bonds in organic chemistry,2 yet significant problems remain unsolved. For unactivated olefins,3 mixtures of Heck isomers are ultimately obtained in low selectivity.4 Despite the recent efforts to provide selective access to branched,5 styrenyl6 or allylic7 olefinated products in the presence of different transition metals, the coupling partners for the Heck reaction of unactivated olefins are restricted to aryl, vinyl or benzyl halides5c,8 which lack detachable β-hydrogens or the C(sp2)−M intermediates generated from the directing grouppromoted C(sp2)−H activation.7,9 In comparison, Heck coupling of unactivated olefins and alkyl halides has received less attention. The intramolecular carbocyclizations of aliphatic alkenes with primary or secondary alkyl electrophiles have been successively reported by Oshima10a, Fu10b, Alexanian10c,d, Pan10e, Carreira,10f Cuerva10g and Jarvo10h through the use of cobalt, palladium, nickel or Ni/Ti co-catalysis (Figure 1a). However, few examples are reported for the intermolecular coupling of non-activated olefins and alkyl halides (Figure 1b).11 Challenges with this chemistry are evident with knowledge of the sluggish oxidative addition of lowvalent metal catalysts to sp3-hybridized electrophiles and the facile β-hydride elimination;12 both would ultimately hamper the further interaction with the already low reactive olefin partner. Additionally, the uncontrollable migratory insertion into the aliphatic olefins and the indiscriminate β-hydride elimination with either Ha or Hb for metal-alkyl intermediate C would result in a mixture of branched olefin product D and linear products E and F. Therefore, the development of a strategy to realize the intermolecular olefination of unactivated olefins and alkyl halides in a selective manner is highly desirable in order to afford a newly complementary type of Heck reaction and ultimately gain access to alkyl olefin products.
Figure 1. Alkylative olefination of unactivated olefins and alkyl halides.
Recently, utilization of alkyl radical species has proven to be a promising approach to advance the intermolecular alkylation of olefins13 by directly using alkyl halides14,15; such species could avoid either slow oxidative addition or β-hydride elimination. However, these alkylative olefination reactions require functionalized alkenes, such as styrenes, acrylates or vinyl ethers as the partners, presumably due to the high reactivity of the alkyl radical, which would be ultimately quenched if not efficiently trapped by the electrophilic acceptor. In this case, we envisaged that installation of a suitable directing group16 on the unactivated olefin substrate might be a potential solution for the intermolecular coupling with alkyl halides. Such a strategy would simulate the intermolecular olefination as an intramolecular version10 and thus increase the chemical reactivity of the non-activated olefins. Moreover, the directing group-coordinated metallacyclic intermediate might result in a conformationally strained intermediate,7,17 which would distinguish the adjacent hydrogen atoms during β-hydride elimination event. Herein, we report the first intermolecular Heck-type coupling of unactivated olefins and alkyl halides by using a directing-group strategy and earth-abundant copper catalyst2g with excellent regio- and stereoselectivity (Figure 1c).
ACS Paragon Plus Environment
Journal of the American Chemical Society 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
Our work was initiated with the reaction of 3-butenoic acid masked as its 8-aminoquinoline (AQ)18 amide 1a and ethyl αbromoisobutyrate 2a in the presence of CuCl and Cs2CO3 in THF at 60 °C (Table 1, entry 1). After 8 h, a mixture of 3a and 3a′ was isolated in 15% yield with a regioisomeric ratio (rr) of 1:1.5, with the majority of the mass balance attributed to recovery of 1a. Alkene substrates with other bidentate auxiliaries19 either afforded trace amount of product (amide-oxazoline) or failed to give any desired product. Increasing the loading of CuCl to 40 mol% improved the yield to 27% with an equivalent ratio of 3a and 3a′ (entry 2). Choice of solvent had a dramatic effect on the reaction (entries 3-7). Nonpolar solvents such as toluene completely suppressed the desired reaction, while polar solvent DMSO gave the product in an 80% isolated yield and a rr of 8:1. Further screening disclosed that a co-solvent system of DMSO/THF increased the yield (82%), regio- (rr = 12:1), and stereoselectivity (E/Z > 20:1) (entry 8, as conditions A). Higher concentrations or elevated temperatures (80 °C) promoted complete consumption of the substrate and resulted in a slightly improved yield; however, only moderate rr value could be obtained (entries 9-10). Other copper sources, for instance, CuI, CuCl2 and Cu(OTf)2 led to the decrease in both yield and rr value (entries 11-13). Control experiments without CuCl or Cs2CO3 provided no product, showing the important roles of both the copper catalyst and base (entries 14-15). Table 1: Optimization of the Reaction Conditionsa
α-substituted terminal alkenes were found to be suitable substrates, including ones containing sterically encumbering substituents such as n-butyl (3b) and isopropyl (3c). Herein, a modified conditions A with higher concentration and elevated temperature was required to accelerate these reactions. When diene or enyne compounds were employed, the olefination proved to be chemoselective with selective functionalization of the β-γ olefin (3d−3g), demonstrating the preference of the five-membered metallacycle. In terms of functional group compatibility, substrates containing methoxy (3h), chlorine (3i) and benzyl groups (3j−3m) with either electron-donating or -withdrawing substituents were all tolerated. For α,α-dimethyl substituted alkenes, the olefination also proceeded smoothly to obtain 3n in 81% yield. Notably, when a substrate having a cis-locked cyclic alkene was tested, the trisubstituted alkene 3o was obtained. The position of double bond at βγ position in 3o was different from the general palladiumcatalyzed Heck reaction of cyclic alkenes, in which conformational rigidity and restricted rotation steered β-hydride elimination away from the newly formed C−C bond.8a,20 Subjecting a 1,1disubstituted alkene to the reaction conditions delivered desired product 3p along with a minor amount of isomer 3p′′ which was generated through the β-hydride elimination of a hydrogen on the methyl group. It should be mentioned that all the above reactions provided excellent regioselectivity and a single E-configuration. Furthermore, the substrates with γ-δ olefin and tri- or tetrasubstituted olefins showed no reactivities (see Table S3 in SI); the former might due to the disfavor of six-membered metallacycle.21 Table 2: Substrate Scope of Electronically Unbiased Alkenesa, b
60, 8 h
yield % (recovery of 1a)b 15 (80)
1:1.5
60, 8 h
27 (68)
1:1
toluene
60, 8 h
0 (94)
-
CuCl
CH3CN
60, 8 h
42 (51)
3:1
5
CuCl
DMF
60, 8 h
54 (35)
4:1
6
CuCl
DMSO
60, 6 h
63 (26)
6:1
7
CuCl
DMSOe
60, 4 h
80 (9)
8:1
CuCl
DMSO/THF (1:1)e
60, 4 h
82 (4)
12:1
9
CuCl
60, 2.5 h
86
6.5:1
10
CuCl
80, 2.5 h
84
5.5:1
11
CuI
60, 8 h
60 (20)
9:1
12
CuCl2
60, 8 h
65 (18)
8:1
13
Cu(OTf)2
60, 8 h
21 (67)
5:1
14
none
60, 12 h
0 (96)
-
15g
CuCl
DMSO/THF (1:1)f DMSO/THF (1:1)e DMSO/THF (1:1)e DMSO/THF (1:1)e DMSO/THF (1:1)e DMSO/THF (1:1)e DMSO/THF (1:1)e
60, 12 h
0 (95)
-
entry
catalyst
solvent
temp (°C)
1
CuCld
THF
2
CuCl
THF
3
CuCl
4
8
rrc (3a:3a′)
a
Conditions: 1a (0.2 mmol) and 2a (0.6 mmol) in solvent (2.0 mL) in the presence of copper (0.08 mmol) and Cs2CO3 (0.2 mmol). b Isolated yields. c The ratio of 3a and 3a′ was determined by 1H NMR. d 20 mmol%. e 1.0 mL solvent. f 0.5 mL solvent. g Without Cs2CO3.
Under the optimized reaction conditions, the substrate scope of the olefins was investigated. As shown in Table 2, a variety of
Page 2 of 7
a
Modified conditions A: 1 (0.2 mmol) and 2a (0.6 mmol) in DMSO/THF (1:1, 0.5 mL) with CuCl (0.08 mmol) and Cs2CO3 (0.2 mmol) at 80 °C. b rr or E/Z is > 20:1 if not stated otherwise. c 100 °C. d 60 °C.
Encouraged by the broad olefin scope, various functionalized alkyl halides were examined (Table 3). Treatment of acyclic αbromo esters with 1a under optimized reaction conditions A gave products 4a−4c with excellent regioselectivities, while cyclic αbromo esters resulted in the formation of 4d and 4e with moderate rr values. Numerous α-bromo alkyl and aryl esters including tertbutyl, benzyl, 4-Me-phenyl and several functionalized alkyl esters were found to be suitable coupling partners (4f−4k). Tertiary alkyl halides with two electron-withdrawing moieties could also be regioselectively converted to the corresponding products 4l−4o in moderate to good yields. This alkylative olefination was opera-
ACS Paragon Plus Environment
Page 3 of 7 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
Journal of the American Chemical Society tive with a variety of alkyl halides bearing different functional groups including benzyl, allyl, silyl ether, methyl ether and chlorine atom to deliver 4p−4t in good yields in a highly stereoselective manner. Gratifyingly, the reaction was compatible with secondary alkyl halides; ethyl 2-bromo-propionate and -valerate led to the formation of 4u and 4v, resepectively, with good E/Z ratios under reaction conditions B which could improve the regioselectivity (rr values are 4:1 and 5:1 for 4u and 4v, respectively, under conditions A), while ethyl α-bromo phenylacetate gave product 4w as single E isomer. Moreover, the olefination could smoothly proceed with α-bromoketone and primary 2-cyanobenzyl bromide to offer 4x and 4y. In some of the above cases, elevated temperatures are needed to obtain better yields. Unfortunately, the unactivated alkyl halides, benzyl bromide and ethyl bromoacetate failed (for details, see Table S3 in SI).
The amides with β-γ internal olefins obtained via our protocol are amenable to further synthetic transformations (Scheme 1). A 2.0 mmol scale synthesis was successfully carried out to give 3a with just a slight decrease in yield and rr value. The 8aminoquinoline moiety could be conveniently removed by treatment with BF3·OEt2 to generate diester 5. The internal double bond could be either efficiently hydrogenated to afford δ-ester amide 6 or dihydroxylated under Sharpless conditions to deliver the corresponding diol intermediate, which cyclized spontaneously to produce lactone 7 in 87% yield. The ethyl ester group on 3a could be selectively reduced with lithium aluminum hydride at 0 °C for 0.5 h to give alcohol 8; when the reaction time was prolonged for 4 h, both the ester and the amide could be reduced and amino alcohol 9 was obtained. Scheme 1. Representative Derivatizations
Table 3: Substrate Scope of Alkyl Halidesa, b
To elucidate the reaction mechanism, control experiments were performed (Scheme 2). Treatment of product 3a in conditions A or B did not change the rr value, indicating that the regioisomer 3a′ was not generated through alkene isomerization. The addition of TEMPO or butylated hydroxytoluene (BHT) into the reaction mixture suppressed the desired reaction and compound 10 could be isolated in the case of TEMPO, which suggested that this reaction involved a radical process. Scheme 2. Mechanistic Investigations
a
Conditions A: 1a (0.2 mmol) and 2 (0.6 mmol) in DMSO/THF (1:1, 1.0 mL) with CuCl (0.08 mmol) and Cs2CO3 (0.2 mmol) at 60 °C; Conditions B: 1a (0.2 mmol) and 2 (0.6 mmol) in DMSO (1.0 mL) with Cu(MeCN)4PF6 (0.10 mmol) and NaOMe (0.2 mmol) at 70 °C. b rr or E/Z is > 20:1 if not stated otherwise. c Copper(I) thiophene-2-carboxylate (0.08 mmol) was used to replace CuCl. d DMSO (1.0 mL) as solvent.
On the basis of previous literature17 and above experimental results, a plausible mechanism is illustrated in Figure 2a. Initially, Cu(I) catalyst coordinates with 1a to afford species M1. Then, a single electron transfer (SET) between M1 and 2a occurs, likely aided by the base additive22 to generate a Cu(II) complex M2 and a carbon radical M3, a process akin to the initiation step in atom transform radical addition (ATRA)23. Subsequent migratory insertion into the unactivated olefin affords a putative Cu(III) intermediate M4.24 Finally, a concerted Hb−Br or Ha−Br elimination,25 followed by protodemetallation would produce the major product 3a and the minor product 3a′, respectively, and regenerate Cu(I) salt.26 To gain a deeper understanding of the excellent regioselectivity in concerted H−Br elimination event, especially the key role of DMSO in this step, DFT calculations were performed at the SMD(DMSO)/(U)M06/[6-31G(d)/LanL2DZ(Cu)] level (see Figures S1-S4 in Supporting Information). As shown in Figure 2b, in the presence of three DMSO molecules, concerted Hb−Br elimina-
ACS Paragon Plus Environment
Journal of the American Chemical Society 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
tion is much easier to occur than concerted Ha−Br elimination, which is consistent with our experimental observations that 3a was predominantly formed. The origin of regioselectivity can be understood by the conformationally strained metallacyclic transition state. Hb−Br elimination occurs concertedly through an eightmembered-ring transition state TS1-Hb with a smaller energy barrier (∆E‡) of 10.9 kcal/mol, whereas Ha−Br elimination (via a six-membered-ring TS1-Ha) requires a larger ∆E‡ value (13.9 kcal/mol).
Page 4 of 7
Computational details Figures S1 – S4, supplementary data Tables S1 – S3, and experimental procedures, analytical data for all new compounds.
AUTHOR INFORMATION Corresponding Author E-Mail:
[email protected] [email protected] [email protected] Author Contributions # C.
T.; R. Z. and B. Z. contributed equally.
Notes The authors declare no competing financial interest.
ACKNOWLEDGMENT We gratefully acknowledge the NNSFC (21702027, 21502017, 21522202, 21773025), Young Scientific Research Foundation of Jilin Province (20180520228JH) and Fundamental Research Funds for the Central Universities (2412017QD010, 2412017FZ015).
REFERENCES
Figure 2. Proposed mechanism and energy profiles of concerted H−Br elimination in the presence of three DMSO.
In summary, we have developed the first Cu-catalyzed intermolecular Heck-type coupling of unactivated olefins and alkyl halides with the assistant of a bidentate auxiliary. This protocol was compatible with 1°, 2°, 3°alkyl bromides and various aliphatic alkenes to produce olefinated products with excellent regio- and stereoselectivity. These resultant internal β,γ-unsaturated amides were proven to be versatile synthetic building blocks in a variety of chemical transformations. Detailed mechanistic studies and DFT calculations indicated a radical pathway involving a dimethyl sulfoxide assisted concerted H−Br elimination event of conformationally strained Cu(III)cyclic transition state. Further applications and mechanistic studies are in progress in our laboratory.
ASSOCIATED CONTENT Supporting Information
(1) (a) Heck, R. F.; Nolley, J. P. Palladium-catalyzed vinylic hydrogen substitution reactions with aryl, benzyl, and styryl halides. J. Org. Chem. 1972, 37, 2320. (b) Mizoroki, T.; Mori, K.; Ozaki, A. Arylation of olefin with aryl iodide catalyzed by palladium. Bull. Chem. Soc. Jpn. 1971, 44, 581. (2) Selected recent reviews: (a) Beletskaya, I. P.; Cheprakov, A. V. The Heck reaction as a sharpening stone of palladium catalysis. Chem. Rev. 2000, 100, 3009. (b) Dounay, A. B.; Overman, L. E. The asymmetric intramolecular Heck reaction in natural product total synthesis. Chem. Rev. 2003, 103, 2945. (c) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Palladiumcatalyzed cross-coupling reactions in total synthesis. Angew. Chem., Int. Ed. 2005, 44, 4442. (d) Bras, J. L.; Muzart, J. Intermolecular dehydrogenative Heck reactions. Chem. Rev. 2011, 111, 1170. (e) Ruan, J.; Xiao, J. From α-arylation of olefins to acylation with aldehydes: a journey in regiocontrol of the Heck reaction. Acc. Chem. Res. 2011, 44, 614. (f) Sigman, M. S.; Werner, E. W. Imparting catalyst control upon classical palladium-catalyzed alkenyl C−H bond functionalization reactions. Acc. Chem. Res. 2012, 45, 874. (g) Wang, S.-S.; Yang, G.-Y. Recent developments in low-cost TM-catalyzed Heck-type reactions (TM = transition metal, Ni, Co, Cu, and Fe). Catal. Sci. Technol. 2016, 6, 2862. (3) For a review, see: Deb, A.; Maiti, D. Emergence of unactivated olefins for the synthesis of olefinated arenes. Eur. J. Org. Chem. 2017, 1239. (4) (a) Dieck, H. A.; Heck, R. F. Organophosphinepalladium complexes as catalysts for vinylic hydrogen substitution reactions. J. Am. Chem. Soc. 1974, 96, 1133. (b) Fall, Y.; Berthiol, F.; Doucet, H.; Santelli, M. Palladium-tetraphosphine catalysed Heck reaction with simple alkenes: influence of reaction conditions on the migration of the double bond. Synthesis 2007, 1683. (c) Calò, V.; Nacci, A.; Monopoli, A.; Cotugno, P. Heck reactions with palladium nanoparticles in ionic liquids: coupling of aryl chlorides with deactivated olefins. Angew. Chem., Int. Ed. 2009, 48, 6101. (5) Selected examples on branched products: (a) Olofsson, K.; Larhed, M.; Hallberg, A. Highly regioselective palladium-catalyzed internal arylation of allyltrimethylsilane with aryl triflates. J. Org. Chem. 1998, 63, 5076. (b) Mo, J.; Xu, L.; Xiao, J. Ionic liquid-promoted, highly regioselective Heck arylation of electron-rich olefins by aryl halides. J. Am. Chem. Soc. 2005, 127, 751. (c) Matsubara, R.; Gutierrez, A. C.; Jamison, T. F. Nickel-catalyzed Heck-type reactions of benzyl chlorides and simple olefins. J. Am. Chem. Soc. 2011, 133, 19020. (d) Qin, L.; Ren, X.; Lu, Y.; Li, Y.; Zhou, J. Intermolecular Mizoroki−Heck reaction of aliphatic olefins with high selectivity for substitution at the internal position. Angew. Chem., Int. Ed. 2012, 51, 5915. (e) Zheng, C.; Wang, D.; Stahl, S. S. Catalyst-controlled regioselectivity in the synthesis of branched conjugated dienes via aerobic oxidative Heck reactions. J. Am. Chem. Soc. 2012, 134, 16496. (f) Tasker, S. Z.; Gutierrez, A. C.; Jamison, T. F. Nickelcatalyzed Mizoroki−Heck reaction of aryl sulfonates and chlorides with electronically unbiased terminal olefins: high selectivity for branched products. Angew. Chem., Int. Ed. 2014, 53, 1858.
ACS Paragon Plus Environment
Page 5 of 7 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
Journal of the American Chemical Society (6) Selected examples on styrenyl products: (a) Delcamp, J. H.; Brucks, A. P.; White, M. C. A general and highly selective chelate-controlled intermolecular oxidative Heck reaction. J. Am. Chem. Soc. 2008, 130, 11270. (b) Werner, E. W.; Sigman, M. S. A highly selective and general palladium catalyst for the oxidative Heck reaction of electronically nonbiased olefins. J. Am. Chem. Soc. 2010, 132, 13981. (c) Werner, E. W.; Sigman, M. S. Operationally simple and highly (E)-styrenyl-selective Heck reactions of electronically nonbiased olefins. J. Am. Chem. Soc. 2011, 133, 9692. (d) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.; Liu, Q.; Zhang, L.; Jiao, N. Ligand-free Pd-catalyzed highly selective arylation of allylic esters with retention of the traditional leaving group. Angew. Chem., Int. Ed. 2008, 47, 4729. (e) Hu, P.; Kan, J.; Su, W.; Hong, M. Pd(O2CCF3)2/benzoquinone: a versatile catalyst system for the decarboxylative olefination of arene carboxylic acids. Org. Lett. 2009, 11, 2341. (f) Ye, Z.; Brust, T. F.; Watts, V. J.; Dai, M. Palladium-catalyzed regio- and stereoselective γ-arylation of tertiary allylic amines: identification of potent adenylyl cyclase inhibitors. Org. Lett. 2015, 17, 892. (g) Zhou, Y.-B.; Wang, Y.-Q.; Ning, L.-C.; Ding, Z.-C.; Wang, W.-L.; Ding, C.-K.; Li, R.-H.; Chen, J.-J.; Lu, X.; Ding, Y.-J.; Zhan, Z.-P. Conjugated microporous polymer as heterogeneous ligand for highly selective oxidative Heck reaction. J. Am. Chem. Soc. 2017, 139, 3966. (7) Selected examples on allylic products: (a) Maity, S.; Kancherla, R.; Dhawa, U.; Hoque, E.; Pimparkar, S.; Maiti, D. Switch to allylic selectivity in cobalt-catalyzed dehydrogenative Heck reactions with unbiased aliphatic olefins. ACS Catal. 2016, 6, 5493. (b) Takahama, Y.; Shibata, Y.; Tanaka, K. Heteroarene-directed oxidative sp2 C−H bond allylation with aliphatic alkenes catalyzed by an (electron-deficient η5-cyclopentadienyl)rhodium(III) complex. Org. Lett. 2016, 18, 2934. (c) Yamaguchi, T.; Kommagalla, Y.; Aihara, Y.; Chatani, N. Cobalt-catalyzed chelation assisted C−H allylation of aromatic amides with unactivated olefins. Chem. Commun. 2016, 52, 10129. (d) Manoharan, R.; Sivakumar, G.; Jeganmohan, M. Cobalt-catalyzed C−H olefination of aromatics with unactivated alkenes. Chem. Commun. 2016, 52, 10533. (e) Maity, S.; Dolui, P.; Kancherla, R.; Maiti, D. Introducing unactivated acyclic internal aliphatic olefins into a cobalt catalyzed allylic selective dehydrogenative Heck reaction. Chem. Sci. 2017, 8, 5181. (8) (a) Yang, Z.; Zhou, J. Palladium-catalyzed, asymmetric Mizoroki−Heck reaction of benzylic electrophiles using phosphoramidites as chiral ligands. J. Am. Chem. Soc. 2012, 134, 11833. (b) Standley, E. A.; Jamison, T. F. Simplifying nickel(0) catalysis: an air-stable nickel precatalyst for the internally selective benzylation of terminal alkenes. J. Am. Chem. Soc. 2013, 135, 1585. (9) (a) Lu, Y.; Wang, D.-H.; Engle, K. M.; Yu, J.-Q. Pd(II)-catalyzed hydroxyl-directed C−H olefination enabled by monoprotected amino acid ligands. J. Am. Chem. Soc. 2010, 132, 5916. (b) Tsai, A. S.; Brasse, M.; Bergman, R. G.; Ellman, J. A. Rh(III)-catalyzed oxidative coupling of unactivated alkenes via C−H activation. Org. Lett. 2011, 13, 540. (c) Li, X.; Gong, X.; Zhao, M.; Song, G.; Deng, J.; Li, X. Rh(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides using activated and unactivated alkenes. Org. Lett. 2011, 13, 5808. (d) Deb, A.; Bag, S.; Kancherla, R.; Maiti, D. Palladium-catalyzed aryl C−H olefination with unactivated, aliphatic alkenes. J. Am. Chem. Soc. 2014, 136, 13602. (e) Wang, Q.; Han, J.; Wang, C.; Zhang, J.; Huang, Z.; Shi, D.; Zhao, Y. Highly siteselective sequential alkenylation of oxalyl amide protected phenylpropylamine derivatives via a seven-membered palladacycle. Chem. Sci. 2014, 5, 4962. (f) Takahama, Y.; Shibata, Y.; Tanaka, K. Oxidative olefination of anilides with unactivated alkenes catalyzed by an (electron-deficient η5cyclopentadienyl)rhodium(III) complex under ambient conditions. Chem. - Eur. J. 2015, 21, 9053. (g) Deb, A.; Hazra, A.; Peng, Q.; Paton, R. S.; Maiti, D. Detailed mechanistic studies on palladium-catalyzed selective C−H olefination with aliphatic alkenes: a significant influence of proton shuttling. J. Am. Chem. Soc. 2017, 139, 763. (h) Seth, K.; Bera, M.; Brochetta, M.; Agasti, S.; Das, A.; Gandini, A.; Porta, A.; Zanoni, G.; Maiti, D. Incorporating unbiased, unactivated aliphatic alkenes in Pd(II)catalyzed olefination of benzyl phosphonamide. ACS Catal. 2017, 7, 7732. (i) Lu, M.-Z.; Chen, X.-R.; Xu, H.; Dai, H.-X.; Yu, J.-Q. Ligand-enabled ortho-C−H olefination of phenylacetic amides with unactivated alkenes. Chem. Sci. 2018, 9, 1311. (10) (a) Fujioka, T.; Nakamura, T.; Yorimitsu, H.; Oshima, K. Cobaltcatalyzed intramolecular Heck-type reaction of 6-halo-1-hexene derivatives. Org. Lett. 2002, 4, 2257. (b) Firmansjah, L.; Fu, G. C. Intramolecular Heck reactions of unactivated alkyl halides. J. Am. Chem. Soc. 2007, 129, 11340. (c) Bloome, K. S.; McMahen, R. L.; Alexanian, E. J. Palladium-catalyzed Heck-type reactions of alkyl iodides. J. Am. Chem. Soc. 2011, 133, 20146. (d) Venning, A. R. O.; Kwiatkowski, M. R.; Peña, J. E.
R.; Lainhart, B. C.; Guruparan, A. A.; Alexanian, E. J. Palladiumcatalyzed carbocyclizations of unactivated alkyl bromides with alkenes involving auto-tandem catalysis. J. Am. Chem. Soc. 2017, 139, 11595. (e) Zhou, W.; An, G.; Zhang, G.; Han, J.; Pan, Y. Ligand-free palladiumcatalyzed intramolecular Heck reaction of secondary benzylic bromides. Org. Biomol. Chem. 2011, 9, 5833. (f) Weiss, M. E.; Kreis, L. M.; Lauber, A.; Carreira, E. M. Cobalt-catalyzed coupling of alkyl iodides with alkenes: deprotonation of hydridocobalt enables turnover. Angew. Chem., Int. Ed. 2011, 50, 11125. (g) Millán, A.; Álvarez de Cienfuegos, L.; Miguel, D.; Campaña, A. G.; Cuerva, J. M. Water control over the chemoselectivity of a Ti/Ni multimetallic system: Heck- or reductive-type cyclization reactions of alkyl iodides. Org. Lett. 2012, 14, 5984. (h) Harris, M. R.; Konev, M. O.; Jarvo, E. R. Enantiospecific intramolecular Heck reactions of secondary benzylic ethers. J. Am. Chem. Soc. 2014, 136, 7825. (11) In the study of Pd-catalyzed intermolecular Heck coupling of tertiary alkyl halides and styrenyl derivatives, an example using methylenecyclopentane is included to give a moderate yield, see: Kurandina, D.; Rivas, M.; Radzhabov, M.; Gevorgyan, V. Heck reaction of electronically diverse tertiary alkyl halides. Org. Lett. 2018, 20, 357. (12) Luh, T.-Y.; Leung, M.-k.; Wong, K.-T. Transition metal-catalyzed activation of aliphatic C−X bonds in carbon–carbon bond formation. Chem. Rev. 2000, 100, 3187. (13) For selected reviews, see: (a) Nishikata, T.; Ishikawa, S. Challenges in the substitution of terminal C−C double bonds with tertiary alkyl groups. Synlett 2015, 26, 716. (b) Tang, S.; Liu, K.; Liu, C.; Lei, A. Olefinic C–H functionalization through radical alkenylation. Chem. Soc. Rev. 2015, 44, 1070. (14) For a review on α-carbonyl alkyl halides, see: Ouyang, X.-H.; Song, R.-J.; Li, J.-H. Developments in the chemistry of α-carbonyl alkyl bromides. Chem. Asian J. 2018, 13, 2316. For selected examples on radical alkenylation of α-carbonyl alkyl halides, see: (a) Liu, C.; Tang, S.; Liu, D.; Yuan, J.; Zheng, L.; Meng, L.; Lei, A. Nickel-catalyzed Heck-type alkenylation of secondary and tertiary α-carbonyl alkyl bromides. Angew. Chem., Int. Ed. 2012, 51, 3638. (b) Jiang, H.; Huang, C.; Guo, J.; Zeng, C.; Zhang, Y.; Yu, S. Direct C−H functionalization of enamides and enecarbamates by using visible-light photoredox catalysis. Chem. - Eur. J. 2012, 18, 15158. (c) Nishikata, T.; Noda, Y.; Fujimoto, R.; Sakashita, T. An efficient generation of a functionalized tertiary-alkyl radical for coppercatalyzed tertiary-alkylative Mizoroki−Heck type reaction. J. Am. Chem. Soc. 2013, 135, 16372. (d) Nakatani, A.; Hirano, K.; Satoh, T.; Miura, M. Nickel-catalyzed direct alkylation of heterocycles with α-bromo carbonyl compounds: C3-selective functionalization of 2-pyridones. Chem. - Eur. J. 2013, 19, 7691. (e) Nishikata, T.; Nakamura, K.; Itonaga, K.; Ishikawa, S. General and facile method for exo-methlyene synthesis via regioselective C−C double-bond formation using a copper–amine catalyst system. Org. Lett. 2014, 16, 5816. (f) Zhang, X.; Yi, H.; Liao, Z.; Zhang, G.; Fan, C.; Qin, C.; Liu, J.; Lei, A. Copper-catalysed direct radical alkenylation of alkyl bromides. Org. Biomol. Chem. 2014, 12, 6790. (g) Zhu, K.; Dunne, J.; Shaver, M. P.; Thomas, S. P. Iron-catalyzed Heck-type alkenylation of functionalized alkyl bromides. ACS Catal. 2017, 7, 2353. (h) Ye, Z.; Cai, X.; Li, J.; Dai, M. Catalytic cyclopropanol ring opening for divergent syntheses of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers. ACS Catal. 2018, 8, 5907. (15) Selected examples on radical alkenylation of unactivated alkyl halides, see: (a) Lebedev, S. A.; Lopatina, V. S.; Petrov, E. S.; Beletskaya, I. P. Condensation of organic bromides with vinyl compounds catalysed by nickel complexes in the presence of zinc. J. Organomet. Chem. 1988, 344, 253. (b) Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K. Cobaltcatalyzed Heck-type reaction of alkyl halides with styrenes. J. Am. Chem. Soc. 2002, 124, 6514. (c) Affo, W.; Ohmiya, H.; Fujioka, T.; Ikeda, Y.; Nakamura, T.; Yorimitsu, H.; Oshima, K.; Imamura, Y.; Mizuta, T.; Miyoshi, K. Cobalt-catalyzed trimethylsilylmethylmagnesium-promoted radical alkenylation of alkyl halides: a complement to the Heck reaction. J. Am. Chem. Soc. 2006, 128, 8068. (d) McMahon, C. M.; Alexanian, E. J. Palladium-catalyzed Heck-type cross-couplings of unactivated alkyl iodides. Angew. Chem., Int. Ed. 2014, 53, 5974. (e) Zou, Y.; Zhou, J. Palladium-catalyzed intermolecular Heck reaction of alkyl halides. Chem. Commun. 2014, 50, 3725. (f) Liu, W.; Li, L.; Chen, Z.; Li, C.-J. A transition-metal-free Heck-type reaction between alkenes and alkyl iodides enabled by light in water. Org. Biomol. Chem. 2015, 13, 6170. (g) Xie, J.; Li, J.; Weingand, V.; Rudolph, M.; Hashmi, A. S. K. Intermolecular photocatalyzed Heck-like coupling of unactivated alkyl bromides by a dinuclear gold complex. Chem. - Eur. J. 2016, 22, 12646. (h) Kurandina, D.; Parasram, M.; Gevorgyan, V. Visible light-induced room-temperature Heck reaction of functionalized alkyl halides with vinyl
ACS Paragon Plus Environment
Journal of the American Chemical Society 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
arenes/heteroarenes. Angew. Chem., Int. Ed. 2017, 56, 14212. (i) Wang, G.-Z.; Shang, R.; Cheng, W.-M.; Fu, Y. Irradiation-induced Heck reaction of unactivated alkyl halides at room temperature. J. Am. Chem. Soc. 2017, 139, 18307. (16) For heteroatom-directed Heck reactions, see: Oestreich, M. Neighbouring-group effects in Heck reactions. Eur. J. Org. Chem. 2005, 783. (17) Conformationally strained intermediate in regioselective β-hydride elimination: (a) Wang, D.-H.; Engle, K. M.; Shi, B.-F.; Yu, J.-Q. Ligandenabled reactivity and selectivity in a synthetically versatile aryl C−H olefination. Science 2010, 327, 315. (b) Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Ligand-accelerated C−H activation reactions: evidence for a switch of mechanism. J. Am. Chem. Soc. 2010, 132, 14137. (c) Liu, B.; Fan, Y.; Gao, Y.; Sun, C.; Xu, C.; Zhu, J. Rhodium(III)-catalyzed N-nitrosodirected C−H olefination of arenes. High-yield, versatile coupling under mild conditions. J. Am. Chem. Soc. 2013, 135, 468. (18) (a) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. Highly regioselective arylation of sp3 C−H bonds catalyzed by palladium acetate. J. Am. Chem. Soc. 2005, 127, 13154. (b) Tran, L. D.; Popov, I.; Daugulis, O. Copper-promoted sulfenylation of sp2 C−H bonds. J. Am. Chem. Soc. 2012, 134, 18237. (19) (a) Rouquet, G.; Chatani, N. Catalytic functionalization of C(sp2)−H and C(sp3)−H bonds by using bidentate directing groups. Angew. Chem., Int. Ed. 2013, 52, 11726. (b) Daugulis, O.; Roane, J.; Tran, L. D. Bidentate, monoanionic auxiliary-directed functionalization of carbon– hydrogen bonds. Acc. Chem. Res. 2015, 48, 1053. (c) Gurak, J. A., Jr.; Engle, K. M. Regioselective hydroamination using a directed nucleopalladation/protodepalladation strategy. Synlett 2017, 28, 2057. (20) Oestreich, M. Breaking news on the enantioselective intermolecular Heck reaction. Angew. Chem., Int. Ed. 2014, 53, 2282. (21) For selected palladium-catalyzed examples, see: (a) O’Duill, M. L.; Matsuura, R.; Wang, Y.; Turnbull, J. L.; Gurak, J. A., Jr.; Gao, D.-W.; Lu, G.; Liu, P.; Engle, K. M. Tridentate directing groups stabilize 6-membered palladacycles in catalytic alkene hydrofunctionalization. J. Am. Chem. Soc. 2017, 139, 15576. (b) Liu, Z.; Ni, H.-Q.; Zeng, T.; Engle, K. M. Catalytic carbo- and aminoboration of alkenyl carbonyl compounds via five- and six-membered palladacycles. J. Am. Chem. Soc. 2018, 140, 3223. (c) Liu, M.; Yang, P.; Karunananda, M. K.; Wang, Y.; Liu, P.; Engle, K. M. C(alkenyl)−H activation via six-membered palladacycles: catalytic 1,3diene synthesis. J. Am. Chem. Soc. 2018, 140, 5805. (d) Wang, H.; Bai, Z.; Jiao, T.; Deng, Z.; Tong, H.; He, G.; Peng, Q.; Chen, G. Palladiumcatalyzed amide-directed enantioselective hydrocarbofunctionalization of unactivated alkenes using a chiral monodentate oxazoline ligand. J. Am. Chem. Soc. 2018, 140, 3542. (e) Wang, C.; Xiao, G.; Guo, T.; Ding, Y.; Wu, X.; Loh, T.-P. Palladium-catalyzed regiocontrollable reductive Heck reaction of unactivated aliphatic alkenes. J. Am. Chem. Soc. 2018, 140, 9332. For selected nickel-catalyzed examples, see: (f) Derosa, J.; van der Puyl; V. A.; Tran, V. T.; Liu, M.; Engle, K. M. Directed nickel-catalyzed 1,2-dialkylation of alkenyl carbonyl compounds. Chem. Sci. 2018, 9, 5278. (g) Lv, H.; Xiao, L.-J.; Zhao, D.; Zhou, Q.-L. Nickel(0)-catalyzed linearselective hydroarylation of unactivated alkenes and styrenes with aryl boronic acids. Chem. Sci. 2018, 9, 6839. (22) (a) Xu, T.; Cheung, C. W.; Hu, X. Iron-catalyzed 1,2-addition of perfluoroalkyl iodides to alkynes and alkenes. Angew. Chem., Int. Ed. 2014, 53, 4910. (b) Xu, T.; Hu, X. Copper-catalyzed 1,2-addition of αcarbonyl iodides to alkynes. Angew. Chem., Int. Ed. 2015, 54, 1307. (23) Eckenhoff, W. T.; Pintauer, T. Copper catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of reducing agents. Catal. Rev.-Sci. Eng. 2010, 52, 1. (24) Selected examples on organocopper(III) species, see: (a) Liu, L.; Zhu, M.; Yu, H.-T.; Zhang, W.-X.; Xi, Z. Organocopper(III) spiro complexes: synthesis, structural characterization, and redox transformation. J. Am. Chem. Soc. 2017, 139, 13688. (b) Suess, A. M.; Ertem, M. Z.; Cramer, C. J.; Stahl, S. S. Divergence between organometallic and single-electrontransfer mechanisms in copper(II)-mediated aerobic C−H oxidation. J. Am. Chem. Soc. 2013, 135, 9797. (25) Xu, J.; Fu, Y.; Luo, D.-F.; Jiang, Y.-Y.; Xiao, B.; Liu, Z.-J.; Gong, T.-J.; Liu, L. Copper-catalyzed trifluoromethylation of terminal alkenes through allylic C−H bond activation. J. Am. Chem. Soc. 2011, 133, 15300. (26) Another possible reaction pathway involving a direct β-H elimination of Cu(III) species M4 has been shown to be unfavorable in energy, see Figure S1 in Supporting Information.
ACS Paragon Plus Environment
Page 6 of 7
Page 7 of 7 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
Journal of the American Chemical Society
ACS Paragon Plus Environment
7
