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Intramolecular Insertions into Unactivated C(sp3)-H Bonds by Oxidatively Generated #-Diketone-#-Gold Carbenes: Synthesis of Cyclopentanones Youliang Wang, Zhitong Zheng, and Liming Zhang J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 02 Apr 2015 Downloaded from http://pubs.acs.org on April 3, 2015
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Intramolecular Insertions into Unactivated C(sp3)-H Bonds by Oxidatively Generated β-Diketone-α-Gold Carbenes: Synthesis of Cyclopentanones Youliang Wang, Zhitong Zheng, and Liming Zhang* Department of Chemistry & Biochemistry, University of California, Santa Barbara, CA 93106 Supporting Information Placeholder ABSTRACT: Generation of reactive α-oxo gold carbene intermediates via gold-catalyzed oxidation of alkynes has become an increasing versatile strategy of replacing hazardous diazo carbonyl compounds with benign and readily available alkynes in the development of efficient synthetic methods. However, one of the hallmarks of metal carbene/carbenoid chemistry, i.e., insertion into an unactivated C(sp3)-H bond, has not be realized. This study reveals for the first time that this highly valuable transformation can be readily realized intramolecularly by oxidatively generated β-diketone-α-gold carbenes using ynones as substrates. Substrate conformation control via the Thorpe-Ingold effect is the key design feature that enable generally good to excellent efficiencies, and synthetically versatile cyclopentanones including spiro-, bridged, and fused bicyclic ones can be readily accessed.
Insertions into unactivated C(sp3)-H bonds by reactive metal carbene/carbenoids are powerful synthetic strategies in the constructions of complex functional structures. The most practiced approach uses diazo compounds as precursors to the reactive metal intermediates, resulting in the development of a plethora of efficient methods and the documentation of an array of elegant applications.1 While many preparative methods have been developed for diazo compounds,1a they remain as highly hazardous materials and are toxic and potentially explosive. Moreover, the reagents used for their synthesis tend to be energetic and thereby put further strain on operational safety. A few years ago we2 developed an intermolecular oxidative gold catalysis that permits facile access to α-oxo gold carbenes (i.e., A) by using benign and readily available alkynes instead of diazo carbonyl compounds3 (Scheme 1A). This approach opens a readily accessible venue to probe the reactivities of these reactive intermediates and explore their synthetic utilities. Indeed, a range of useful synthetic methods have been developed by us4 and others5 based on this non-diazo strategy. From all the documented reactivities, α-oxo gold carbenes appear to be more electrophilic than their Rh carbenoid counterparts and react readily with various nucleophiles including solvents,6 hence displaying more of the characteristics of gold-stabilized carbocations.7 As a consequence, insertions into C(sp3)-H bonds, hallmarks of carbene reactivities, have so far not been observed with thus-generated α-oxo gold carbenes, despite a formal instance in the versatile gold-catalyzed oxidative formation of cyclopentenone reported by Liu,5j where the formation of an α-oxo gold carbene intermediate is deemed unlikely (Scheme 1B), and cases involving intramolecularly generated more electron-rich counterparts.8 Notwithstanding, the gold carbenes/carbenoid generated from ethyl diazoacetate (EDA) have been shown to be capable of inserting into the C-H bonds of
alkanes (used as solvent, Scheme 1C).3a To reconcile these apparent difference in reaction outcomes, we reasoned that α-oxo gold carbenes are capable of C-H insertions but prefer electrophilic reactions.3b In the cases of their oxidative generations, various nucleophiles present in the reaction mixture, such as the oxidants, their reduced counterparts and even solvents,6,9 can readily trap these highly electrophilic species and thereby divert them from significant and observable C-H insertions. We anticipated that by suitable substrate design and by optimization of reaction conditions insertions into unactivated C(sp3)-H bonds by oxidatively generated α-oxo gold carbenes can be realized and become synthetically useful, thereby circumventing the use of diazo substrates in this class of highly valuable transformations. Herein we disclose our preliminary results on this topic. A. Oxidative generation of -oxo gold carbene exter nal oxidant
O-Z
O
[Au]
Z
O high electrophilic intermediate [Au] A
[Au]
[Au]
[Au]
O
equivalent
hazardous and potentially explosive
O-Z N2 B. W ork by Liu Me +
N+ Me O1a (3 equiv)
IPrAuCl/AgNTf 2 (5%) DCE, 80 C, 2.5 h O
83%
C. W ork by Nolan, Díaz-Requejo and Pérez IPrAuCl Me Me O NaBArF4 + Me N2 Me Me OEt 90% Me Me solvent 4.9
CO2Et
Me Me
Me
CO2Et
Me :
1
Scheme 1. α-Oxo gold carbenes and C-H insertion reactions. At the outset, we chose the alkynone 2a as the substrate (Table 1) for the following considerations: a) the likely generated βdiketone-α-gold(I) carbene (i.e., B, Scheme 2) upon gold-promoted oxidation of the alkynone moiety should be even more electrophilic than the α-oxo gold carbene counterpart A and thereby more reactive toward C-H insertion, b) the additional acyl group would provide extra steric hindrance to dissuade intermolecular side reactions, and c) the gem-dimethyl groups would provide beneficial conformation control of the carbon backbone due to the ThorpeIngold effect. Much to our delight, C-H insertions occurred even with Ph3PAuNTf2 in the presence of 8-methylquinoline N-oxide (1a) and three different C-H insertion products, i.e., 3a-5a, were
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yieldb ent catalyst (5 mol %) N-oxide ry 3a/4a/5ac 6a 1a 30% (9.5/1/1.1) 7% 1 Ph3PAuNTf2 61% (1.1/1/1) 20% 1a 2 BrettPhosAuNTf2 63% (7.9/1/0) 11% 1a 3 IPrAuNTf2 1a 57% (15.7/1/0) 7% 4 IMesAuCl/AgNTf2 70% (6.7/1/0) 12% 1a 5 MorDalPhosAuNTf2 59% (7.7/1/0) 7% 1a 6 L1AuCl/AgNTf2 1a 65% (10.0/1/0) 10% 7 L2AuCl/AgNTf2 1a 68% (11.0/1/0) 8% 8 L3AuCl/AgNTf2 1a 72% (13.2/1/0) 7% 9 L4AuCl/AgNTf2 1a 67% (12.8/1/0) 12% 10 L4AuCl/AgOTf 1a 67% (12.2/1/0) 10% 11 L4AuCl/AgSbF6 71% (9.5/1/0) 5% 12d L4AuCl/NaBArF4 (10 mol %) 1a 1b 84%e (13.7/1/0) 8% 13 L4AuCl/AgNTf2 75% (13.0/1/0) 6% 1c 14f L4AuCl/AgNTf2 1b 74% (13.8/1/0) 10% 15 IMesAuCl/AgNTf2 a [2a] = 0.05 M. b Estimated by 1H NMR using diethyl phthalate as the internal reference. c As mixtures of tautomers and diastereomers. d 12 h. Isolated yield. e 77% isolated yield. f Overnight.
formed, albeit only in a 27% combined yield as mixtures of tautomers and insertion products, i.e., 3a-5a, were formed, albeit only in a 30% combined yield as mixtures of tautomers and diastereomers at the β-diketone moieties (Table 1, entry 1). In addition, acetophenone (6a) was also formed in 7% yield. While the formation of the major product, cyclopentanone 3a, via carbene insertion into γ-CH2 was expected, the formations of the minor cyclobutanones 4a and 5a via carbene insertion into β-CH2 and βCH3, respectively, were somewhat surprising, especially in the latter case. These results indicate that the gold carbene generated is indeed highly reactive and very capable of inserting into unactivated C(sp3)-H bonds. With the bulky and electron-rich BrettPhos as ligand, the combined yield of the C-H insertion products was much improved, although the regioselectivity suffered (entry 2). When the N-hetereocyclic carbene IPr was used as ligand, the reaction yield was moderate but with serviceable regioselectivity (entry 3). Notable in this case is that there was no insertion into the methyl C-H bond, indicating the gold carbene intermediate is less reactive than those generated in entries 1 and 2, consistent with the fact that IPr is a stronger σ-donor than phosphines. This was also the case with IMes, another frequently used NHC, despite an even better selectivity of the cyclopentanone 3a over the cyclobutanone 4a (15.7:1) was realized (entry 4). We have previously reported that P,N-bidentate ligands can attenuate the reactivity of α-oxo gold carbenes via the formation of triscoordinated gold centers.4b-e Indeed, when Mor-DalPhos11 was used, the insertion into methyl C-H bonds likewise did not occur, while the reaction yield and the ratio of 3a and 4a remained moderate (entry 5). Other P,N-bidentate ligands, i.e., L1-L4, were also examined. In all the cases, no cyclobutanone 5a was detected (entries 6-9). While the substitution of methyl groups on the
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morpholine ring of Mor-DalPhos showed slight increase of selectivity of 3a over 4a (comparing entries 5 and 6), the ligands containing a piperidine ring, i.e., L2, and methyl-substituted ones, i.e., L3 and L4,4d led to steadily improved selectivities and yields, the trend of which appears correlate to the increasing basicity of the nitrogen atom and shielding by the piperidine ring (entries 7-9). A good regioselectivity of 13.2 /1 was achieved with L4 as ligand (entry 9), along with an acceptable 72% yield. Replacing NTf2with other counter anions led to lower selectivities and/or decreased reaction yields (entries 10-12). The oxidant was then varied. 8Isopropylquinoline N-oxide (1b),4f a more hindered oxidant, led to an improved 84% yield (entry 13), while others including 2,6dichloropyridine N-oxide (entry 14) were not as effective. Finally, replacing L4 with IMes led to a slightly better selectivity but a lower yield (comparing entry 15 with entry 13). In all these cases, acetophenone was detected as a side product.
Scheme 2. A proposed mechanism for the reaction of 2a. A plausible mechanism is proposed in Scheme 2 to explain the reaction outcomes and in particular the formation of 6a. Based on the ease of insertion into unactivated C(sp3)-H bonds including those of methyl, it is likely that the β-diketone-α-gold carbene B is generated as the key reactive intermediate via oxidative gold catalysis and, moreover, the C-H insertions are concerted. On the other hand, a competitive hydride abstraction12 of the β-methylene group would lead to the formation of the carbocation intermediate C, which would then undergo C-C bond fragmentation to deliver the acylketene D. This intermediate could then undergo hydrative decarboxylation to yield 6a by adventitious H2O during the reaction and/or upon workup. In addition, the formation of the other side product, i.e., 2-methyl-2-octene, in the process is supported by GCMS analysis of one of the reaction mixtures. The likelihood that both C and 4a might be formed via the same transition state but with subsequent bifurcation13 is intriguing and will be subjected to future DFT calculations. Mindful of the beneficial Thorpe-Ingold effect in facilitating the C-H insertion, we first probed the reaction scope using ynones possessing fully substituted α-carbons under the optimal conditions outlined in Table 1, entry 13. As shown in Table 2, the phenyl group of 2a can be replaced with an n-butyl in the case of the ynone substrate 2b, and the gold catalysis was highly efficient and regioselective (entry 1). Insertion by the gold carbene intermediate into a sterically more hindered C-H bond, as in the case of 2c, was more efficient and selective with IMesAuCl/AgNTf2 (5 mol%) as catalyst (entry 2); moreover, in this case no product derived from insertion into the more labile methine C-H bond was detected, indicating a strong preference of forming five-membered rings. The expected insertion into an ethereal and hence activated C-H bond in the case of 2d, however, did not occur. With IPrAuNTf2 as catalyst, the cyclic acetal 3d was isolated in 60% yield along with 12% of 3d’(entry 3). The former product must be formed via an initial hydride abstraction12 at the γ-CH2 followed by cyclization of the gold enolate oxygen, and the latter via the same process as 2methyl-2-octene in Scheme 2. It is important to point out that the
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Table 2. Scope with ynones featuring fully substituted αcarbons a entry
substrate 2
yieldb
product 3
Me Me O
1
94% (>25/1)c
n
Bu
2b
n
Bu
3b
Me Me
2d,e
O
78% (15/1)c
Me Me
Ph 2c Me Me O
3f
3c
60%
TIPSO Ph
2d
3d Me
Me O
4 Bz
2e
3e
5 2f
96%
(18.2/1)c
3f
72% (trans/cis : >20/1) 85%
6 2g
3g
2h
3h
75%
7 Bz O
f
8
76%
OTBS
2i
Reaction conditions: 2 (0.05 M in PhF), L4AuCl/AgNTf2 (5 mol%), 1b (2 equiv), rt, 2 h. b Isolated yield. c Cyclopentanone 3/cyclobutanones 4 and 5. d IMesAuCl/AgNTf2 (5 mol%) as catalyst. e 58% yield and 3/(4+5) = 2/1 with L4AuCl/AgNTf2 as catalyst. f IPrAuNTf2 (5 mol%) as catalyst Me Me 3d'
Table 3. Constructions of fused bicyclic cyclopentanonesa entry
substrate 2
2j
Ph
O
2
48% 2k
Ph Me
3d
absence of any product of type 3d in the prior cases as well as in the ensuing cases suggest that insertions into non-activated C-H bonds by β-diketone-α-gold carbenes might not involve similar hydride abstractions and hence likely be concerted. Entries 4-6 show the reactions of ynone substrates possessing a cyclohexane ring at the γ-, β-, α-carbon, and the formed cyclopentanone products featured spiro-, fused, and bridged bicyclic skeletons, respectively, in good to excellent yields. Of note is that 3f was formed predominantly as the 5,6-trans-fused isomer, and the high efficiency of forming 3g, despite the strained nature of the bicycle[3.2.1]octane ring. The TIPS-protected hydroxylalkynone 2h, readily accessible from cyclohexanone in three steps by using Katritzky’s alkynylacyl anion equivalent, i.e., deprotonated 1(benzotriazol-1-yl)propargyl ethyl ether,14 also underwent the oxidative gold catalysis in good efficiency (entry 7). Overall, this entry opens a facile four-step strategy to construct the synthetically versatile bridged bicycle from cyclohexanone. By following the same 4-step sequence with the exception of the gold catalyst, the TBSO-substituted hexahydro-1,4-methanopentalen-2(1H)-one 3i was prepared from norcamphor in a good yield (entry 8). Also
3j
(trans/cis: >8/1)
O
OTBS
3i' (20%)
40%
1c
Ph
O
yieldb
cyclopentanone 3
O
3i
a
TIPSO
isolated in the reaction was the side product 3i’, the formation of which can be ascribed to silyloxy oxygen trapping of the carbene center followed by silyl migration. This finding suggests the importance of properly masking a competing nucleophilic site in order to facilitate the desired C-H insertion process. To further explore the synthetic utility of this C-H insertion chemistry, we turned our attention to substrates offering access to fused bicyclic cyclopentanones, as in the case of 2f (cf. Table 2, entry 5). For the cases examined in Table 3, IPrAuNTf2 turned out to be the optimal catalyst, and in some cases (entries 3-5) the oxidant loadings were lowered to 1.5 equiv. In the absence of the Thorpe-Ingold effect, the cyclohexyl-containing alkynone 2j still underwent the desired reaction, affording mainly the trans-fused product 3j albeit in only 40% yield (entry 1). The use of a C-C double bond to limit conformational flexibility in the case of 2k did improve the reaction to some extent (entry 2).5j Much to our delight, the Thorpe-Ingold effect again significantly facilitates the reaction, and as shown in entries 3-4 the bicyclic cyclopentanones 3l and 3m were both formed in good yields. Different from the cases of 3f and 3j, they are mainly or exclusively cis-fused, likely the result of the gold carbene moiety mostly or completely residing at the cyclohexane ring axial position. The symmetric nature of the 1,3diketone-2-gold carbene generated in these oxidative gold catalysis suggests that 3m should be accessible from the isomeric phenyl alkynyl ketone 2m’. Indeed, the reaction of 2m’proceeded with an identical yield and the same exclusive cis-selectivity (entry 5). This oxidative gold catalysis was also conducive to the construction of 5,5-fused cyclopentanones, which are exclusive cis-fused (entries 6-8). Again, the phenyl alkynyl ketones 2o and 2p were suitable substrates. The low yield of the latter (entry 8) again reflected the importance of sterically shielding of the HO group as the side product 3p’, owing to the competing oxygen attack, was formed in an equal amount.
83% (cis/trans: 3.5/1)
O
Ph OTIPS
4d
3k
2l
3l
O
75% (cis only) 2m
Ph
3m
OTIPS
5d
75% (cis only)
Bz
2m’
3m 67% (cis only)
6 2n
3n 67% (cis only)
7
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2o
3o
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Corresponding Author
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8
40% 2p
Notes
3p
The authors declare no competing financial interests.
a
Reaction conditions: 2 (0.05 M in PhF), IPrAuNTf2 (5 mol %), 1b (2 equiv), rt, 2 h. b Isolated yield. c DCE as solvent. d 1.5 equiv. of 1b.
ACKNOWLEDGMENT The authors thank NSF (CHE-1301343) and NIH (R01 GM084254) for financial support.
To gain additional insights to the reaction mechanism, we examined the gold-catalyzed reactions of the α-diazo β-diketone 7 (Scheme 3A). While too slow with either IPrAuNTf2 or L4AuNTf2, the reaction in the presence of tBuBrettPhosAuNTf2 (5 mol%) proceeded to completion in 4 days. In comparison, the corresponding oxidative gold catalysis using the same catalyst took only 2 h and, moreover, afforded higher yields, highlighting the additional advantages of our oxidative gold catalysis over the diazo approach. Importantly, the nearly identical ratios of 3a/4a/5a corroborate the likely formation of a common reactive intermediate (i.e., B) in both cases. The C-H insertion step was probed by deuterium kinetic isotope effect (KIE). As shown in Scheme 3B, in the internal competition a KIE of 2.34 was observed.15 This value indicates that the C-H bond is significantly elongated in the insertion transition state. In contrast, inverse KIEs were observed with donor-substituted gold carbenes.8c A
t Me Me BuBrettPhosAuNTf 2 (5 mol %), 1b (1.5 equiv), DCE, 2 h O 23% (1.00) 36% (1.55) 16% (0.70) 19% (0.82) n Me Me Bu Me C 6H 13 O O O 2a Ph Me O Me Ph Me n Me Me Bu C 5 H11 Bz Bz Bz 6a 5a O 4a 3a nBu
N2
Bz
7 B
n
Me Me H
Bu
19% (1.00) tBuBrettPhosAuNTf
2
L4AuCl/AgNTf2 O (5 mol%) 1b (2 equiv) PhF, rt, 2 h K H/ K D = 2.34
14% (0.73)
13% (0.68)
(5 mol %), DCE, 4 days Me
Me
Me
D
Bz
3a-d (43.7%)
nBu
Me
Me
O
Me O n Bu
O nBu
D
Ph 90.2% 2a-d
30% (1.56)
H
Bz 3a (26.3%)
Bz D H 4a-d (8%)
Scheme 3. Mechanistic studies. In summary, we have discovered for the first time that oxidatively generated gold carbenes in the form of β-diketone-αgold carbenes can easily insert intramolecular into unactivated C(sp3)-H bonds in likely concerted manners. Substrate conformation control via the Thorpe-Ingold effect is the key design feature that enable the generally good to excellent efficiencies in the examined cases. This novel reactivity offers efficient access to synthetically versatile cyclopentanones including spiro-, bridged, and fused bicyclic ones from readily available ynone substrates. This study represents a remarkable advance in replacing toxic and potentially explosive diazo ketones with benign and easily available alkynes in achieving one of the hallmark and most valuable transformation of metal carbenes/carbenoids, i.e., insertions into unactivated C(sp3)-H bonds.
ASSOCIATED CONTENT / Supporting Information Experimental details, compound characterization and spectra. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
[email protected] REFERENCES (1) For reviews, see: a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern catalytic methods for organic synthesis with diazo compounds: from cyclopropanes to ylides; Wiley: New York, 1998; b) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861; c) Taber, D. F. In Carbon-Carbon σ -Bond Formation; Pattenden, G., Ed.; Pergamon Press: Oxford, England ; New York, 1991; Vol. 3, p 1045. (2) Zhang, L. Acc. Chem. Res. 2014, 47, 877. (3) For selected examples using diazo substrates, see: a) Diaz-Requejo, M. M.; Perez, P. J. Chem. Rev. 2008, 108, 3379; b) Fructos, M. R.; Belderrain, T. R.; de Fremont, P.; Scott, N. M.; Nolan, S. P.; DiazRequejo, M. M.; Perez, P. J. Angew. Chem. Int. Ed. 2005, 44, 5284; c) Prieto, A.; Fructos, M. R.; Mar Díaz-Requejo, M.; Pérez, P. J.; PérezGalán, P.; Delpont, N.; Echavarren, A. M. Tetrahedron 2009, 65, 1790; d) Jadhav, A. M.; Pagar, V. V.; Liu, R.-S. Angew. Chem., Int. Ed. 2012, 51, 11809; e) Briones, J. F.; Davies, H. M. L. J. Am. Chem. Soc. 2012, 134, 11916; f) Cao, Z.-Y.; Wang, X.; Tan, C.; Zhao, X.-L.; Zhou, J.; Ding, K. J. Am. Chem. Soc. 2013, 135, 8197; g) Yu, Z.; Ma, B.; Chen, M.; Wu, H.-H.; Liu, L.; Zhang, J. J. Am. Chem. Soc. 2014, 136, 6904; h) Xi, Y.; Su, Y.; Yu, Z.; Dong, B.; McClain, E. J.; Lan, Y.; Shi, X. Angew. Chem., Int. Ed. 2014, 53, 9817. (4) For our selected work, see: a) Ye, L.; Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258; b) Wu, G.; Zheng, R.; Nelson, J.; Zhang, L. Adv. Synth. Catal. 2014, 356, 1229; c) Ji, K.; Zhang, L. Org. Chem. Front. 2014, 1, 34; d) Ji, K.; Zhao, Y.; Zhang, L. Angew. Chem., Int. Ed. 2013, 52, 6508; e) Luo, Y.; Ji, K.; Li, Y.; Zhang, L. J. Am. Chem. Soc. 2012, 134, 17412; f) Lu, B.; Li, C.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 14070. (5) For selected work, see: a) Ghorpade, S.; Su, M.-D.; Liu, R.-S. Angew. Chem., Int. Ed. 2013, 52, 4229; b) Vasu, D.; Hung, H.-H.; Bhunia, S.; Gawade, S. A.; Das, A.; Liu, R.-S. Angew. Chem., Int. Ed. 2011, 50, 6911; c) Qian, D.; Zhang, J. Chem. Commun. 2012, 48, 7082; d) Davies, P. W.; Cremonesi, A.; Martin, N. Chem. Commun. 2011, 47, 379; e) Henrion, G.; Chavas, T. E. J.; Le Goff, X.; Gagosz, F. Angew. Chem., Int. Ed. 2013, 52, 6277; f) Xu, M.; Ren, T.-T.; Li, C.-Y. Org. Lett. 2012, 14, 4902; g) Wang, T.; Shi, S.; Hansmann, M. M.; Rettenmeier, E.; Rudolph, M.; Hashmi, A. S. K. Angew. Chem., Int. Ed. 2014, 53, 3715; h) Shi, S.; Wang, T.; Yang, W.; Rudolph, M.; Hashmi, A. S. K. Chem. Eur. J. 2013, 19, 6576; i) Sun, N.; Chen, M.; Liu, Y. J. Org. Chem. 2014, 79, 4055; j) Bhunia, S.; Ghorpade, S.; Huple, D. B.; Liu, R.-S. Angew. Chem., Int. Ed. 2012, 51, 2939; k) Chen, M.; Chen, Y.; Sun, N.; Zhao, J.; Liu, Y.; Li, Y. Angew. Chem., Int. Ed. 2015, 1200. (6) He, W.; Xie, L.; Xu, Y.; Xiang, J.; Zhang, L. Org. Biomol. Chem. 2012, 10, 3168. (7) Wang, Y.; Muratore, M. E.; Echavarren, A. M. Chem. - Eur. J. 2015, DOI: 10.1002/chem.201406318. (8) a) Lemiere, G.; Gandon, V.; Cariou, K.; Hours, A.; Fukuyama, T.; Dhimane, A. L.; Fensterbank, L.; Malacria, M. J. Am. Chem. Soc. 2009, 131, 2993; b) Escribano-Cuesta, A.; López-Carrillo, V.; Janssen, D.; Echavarren, A. M. Chem. - Eur. J. 2009, 15, 5646; c) Horino, Y.; Yamamoto, T.; Ueda, K.; Kuroda, S.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 2809. (9) He, W.; Li, C.; Zhang, L. J. Am. Chem. Soc. 2011, 133, 8482. (10) See supporting information for details. (11) Hesp, K. D.; Stradiotto, M. J. Am. Chem. Soc. 2010, 132, 18026. (12) a) Bhunia, S.; Liu, R.-S. J. Am. Chem. Soc. 2008, 130, 16488; b) Bolte, B.; Gagosz, F. J. Am. Chem. Soc. 2011, 133, 7696. (13) For an example of gold catalysis involving bifurcation, see: Ye, L.; Wang, Y.; Aue, D. H.; Zhang, L. J. Am. Chem. Soc. 2012, 134, 31. (14) Katritzky, A. R.; Lang, H. J. Org. Chem. 1995, 60, 7612. (15) Similar KIEs are reported on metal carbene insertions into unactivated C(sp3)-H bonds. For references, see: a) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem. Soc. 2000, 122, 3063; b) Mbuvi, H. M.; Woo, L. K. Organometallics 2008, 27, 637.
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