Communication Cite This: J. Am. Chem. Soc. 2018, 140, 10950−10954
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Carboiodination Catalyzed by Nickel Hyung Yoon,† Austin D. Marchese,† and Mark Lautens* Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada
J. Am. Chem. Soc. 2018.140:10950-10954. Downloaded from pubs.acs.org by UNIV OF SOUTH DAKOTA on 09/12/18. For personal use only.
S Supporting Information *
Scheme 1. Previous Work on the Ni-Catalyzed Arylcyanation and Pd-Catalyzed Carbohalogenation Reaction
ABSTRACT: A novel nickel-catalyzed cycloisomerization reaction forming a new carbon−carbon bond while preserving the carbon−halogen bond has been developed. A cheap and readily available Ni-catalyst is employed to generate nitrogen containing heterocycles in good to excellent yields and the procedure is readily scalable. The more readily available aryl bromides were also cyclized with the addition of potassium iodide to generate the respective alkyl iodides. A rare dual ligand system employing a bisphosphine and bisphosphine monoxide was used to achieve enantioenriched products.
N
ickel-catalyzed processes continue to be of interest from researchers in academia and industry due to their low cost and diverse reactions.1 In particular, advances in Nicatalyzed cross coupling reactions in the formation of new carbon−carbon and carbon−heteroatom bonds have been achieved1−4 though the preinstalled coupling moiety disappears in the process. Despite the remarkable progress made, highly atom economical methodologies remain scarce.5 We envisioned that a cycloisomerization reaction would represent an ideal platform for the development of a novel, perfectly atom economical Ni-catalyzed transformation. Notably in 2008, the Jacobsen6 and Hiyama7 groups concurrently disclosed the intramolecular Ni- and Lewis acid cocatalyzed arylcyanation reaction of arylnitriles to generate the respective alkylnitriles (Scheme 1A). However, the isomerization reaction of organic halides via Ni-catalysis remains unprecedented. Transition-metal catalyzed synthesis of halogenated compounds have also attracted tremendous attention as organic halides are found in various natural products, bioactive molecules and undoubtedly represent valuable and versatile synthetic precursors.8−10 In 2010 and 2011, our group described the first Pd-catalyzed reactions based on reversible oxidative addition of C−X bonds. A particular focus was on the cycloisomerization (carbohalogenation) reaction forming heterocycles wherein the carbon−iodine bond was regenerated at the end of the catalytic cycle (Scheme 1B).11 We showed that the use of an exceptionally bulky and electron rich phosphine ligand such as QPhos or P(tBu)3 facilitated reversible oxidative addition. The Tong group also independently described the Pd-catalyzed carboiodination reaction utilizing vinyl iodides at higher temperatures in the presence of excess dppf to generate 1,2,3,6-tetrahydropyridines.12 Following these seminal reports, several related methodologies were reported13 including the reductive elimination of C−Br and C−Cl bonds,14 highly diastereoselective transformations,15 as well as the use of HX salts as external halogen sources.16 As © 2018 American Chemical Society
part of our ongoing research interest and aim to advance the carbohalogenation reaction, we sought to employ nickel, a cheaper, base metal equivalent, to provide a new perspective in generating the respective alkyl halides. Herein, we describe the first Ni-catalyzed intramolecular carbohalogenation reaction, using an inexpensive and easily accessible catalyst, to generate valuable halogenated 3,3disubstituted heterocycles in good to excellent yield (Scheme 1C). Inexpensive, readily available phosphine and phosphite ligands can be used in place of the sterically bulky ligands typically required for the analogous Pd process. In addition to the cycloisomerization reaction, the synthesis of alkyl iodides from the respective aryl bromide and additional potassium iodide is reported. Moreover, a significant limitation in the Pdcatalyzed carboiodination reaction was the lack of an asymmetric variant. We discovered that using an unusual dual ligand system combining a bisphosphine and bisphosphine monoxide, generated the respective chiral iodinated oxindoles that were previously inaccessible. At the outset of our investigation, we selected substrate 1a for the optimization of the conditions for the nickel-catalyzed carboiodination reaction. Utilizing the bulky QPhos ligand previously employed for the Pd-catalyzed variant, 1a was subjected to NiBr·glyme, ligand and manganese as the reducing agent to give 2a in 45% yield (Scheme 2). The Received: July 2, 2018 Published: August 23, 2018 10950
DOI: 10.1021/jacs.8b06966 J. Am. Chem. Soc. 2018, 140, 10950−10954
Communication
Journal of the American Chemical Society
Having established the optimized reaction conditions, we investigated the substrate scope of this reaction (Scheme 3).
Scheme 2. Initial Hit
Scheme 3. Ni-Catalyzed Carboiodination*
structure of 2a was unambiguously determined by spectroscopic analysis and single crystal X-ray crystallography. After screening of the reaction parameters, the optimal conditions were found to be NiI2(PPh3)2 as the precatalyst and manganese as the reducing agent in toluene at 100 °C for 24 h (90% yield). A series of variations from the standard reaction conditions were performed to examine their effects on the efficiency of the transformation (Table 1). Table 1. Ni-Catalyzed Carboiodination: Variation from the Standard Reaction Conditions
Entry
Variation from “standard conditions”
Yield 2a (%)a,b
1 2 3 4c 5e 6 7f 8 9 10g 11
None NiBr2(PPh3)2 instead of NiI2(PPh3)2 NiCl2(PPh3)2 instead of NiI2(PPh3)2 NiI2 and Phend instead of NiI2(PPh3)2 No Ni catalyst No Mn Ni(COD)2 and PPh3 instead of NiI2(PPh3)2 Zn instead of Mn Dioxane instead of PhMe 5 mol % instead of 10 mol % 80 °C instead of 100 °C
(90) 79 N.R. N.R. N.R. N.R. 81 36 80 50 54
*
Reactions were run on 0.2 mmol scale. Isolated yields. aReaction was run on 2.75 mmol scale. bReaction was run for 48 h. cReaction was heated to 120 °C. dNiI2 (10 mol %) and P(OiPr)3 (20 mol %) was used at 80 °C.
The weakly electron-rich acrylamides 1b and 1c provided 2b and 2c in good yield to excellent yields (85% and 92% yield, respectively). Other halogens such as chloride and fluoride were tolerated in the isomerization reaction (2d and 2e, 82% yield). The trifluoromethylated acrylamide 1f was found to be less reactive under the reaction conditions and required elevated temperature and longer reaction time to attain 2f in moderate yield (120 °C and 48 h). Removable N-protecting groups such as −MOM and −Bn afforded the corresponding products in moderate to excellent yields. However, both reactions required additional time to reach full conversion (2g and 2h, 68 and 91% yield respectively). Introduction of a 2methylated pendant aromatic group afforded 2i in diminished yield, suggesting that steric encumbrance impacts the efficiency of the cyclization (38% yield). The fluorinated pendant aromatic ring was well tolerated (2j, 76% yield). Upon changing the substituent on the alkene from an aromatic group to an alkyl group, a different catalyst system was required to give the corresponding halogenated oxindoles. The combination of NiI2 and P(OiPr)3 gave the desired cycloisomerized product in higher yields. Methyl- and benzylacrylamides 1k and 1l cyclized in good yields (78% and 75%, respectively).17 In contrast to 2i, bulkier substituent such as isopropyl afforded 2m in 72% yield. The n-butyl substituted substrate 1n required longer reaction times to reach full conversion (48 h and 58% yield). Finally, to test the scalability of this protocol, model acrylamide 1a was cyclized on gram scale to provide 2a in 86% yield. Unfortunately, unprotected acrylamides and monosub-
a
Determined by 1H NMR analysis of the crude reaction mixtures using 1,3,5-trimethoxybenzene as internal standard. bIsolated yields in parentheses. c10 mol % of NiI2 was used. dPhen = 1,10phenanthroline. e20 mol % of PPh3 was added. fNo Mn was added and 40 mol % of PPh3 was added. gReaction was run at 0.4 M. N.R. = no reaction observed.
The use of similar catalysts but with a different halide counterion (i.e., NiBr2(PPh3)2 and NiCl2(PPh3)2) led to lower yield or no formation of 2a (entry 2 and 3 respectively). Of note, no halogen scrambling was observed when NiBr2(PPh3)2 was used. Employing 1,10-phenanthroline (Phen), a bidentate N,N ligand commonly used in Ni-catalysis, failed to give the desired reaction (entry 4). Removing the precatalyst or the reducing agent led to no reaction (entry 5 and 6). Interestingly, Ni(COD)2 and PPh3 gave the desired product in slightly lower yield in the absence of manganese (entry 7). These results suggest that the manganese is exclusively used as the reducing agent for the in situ generation of the active catalyst. Another commonly used reducing agent such as zinc gave the product in reduced yield (entry 8). Dioxane was also found to be a suitable solvent but provided the product in lower yield (80% yield, entry 9). Finally, a lower catalyst loading or lower temperature stunted the formation of 2a (entry 10 and 11).17 10951
DOI: 10.1021/jacs.8b06966 J. Am. Chem. Soc. 2018, 140, 10950−10954
Communication
Journal of the American Chemical Society stituted olefins were found to be unsuitable substrates for this transformation. Of note, in the presence of a second acceptor where a competing 5-exo-trig cyclization is possible, 1o selectively cyclized on the methacryl group to yield 2o exclusively (Scheme 4). Notably, the absence of the carbonyl functionality
Scheme 5. Ni-Catalyzed Halogen Exchange-Induced Carboiodination*
Scheme 4. Directed Ni-Catalyzed Carboiodination*
*
Reactions were run on 0.2 mmol scale. Isolated yields. aNiI2 (10 mol %) and P(OiPr)3 (20 mol %) was used at 80 °C. bReaction was run for 48 h.
Scheme 6. Enantioselective Ni-Catalyzed Carboiodination*
* Reactions were run on 0.2 mmol scale. Isolated yields. aNiI2 (10 mol %) and P(OiPr)3 (20 mol %) was used at 80 °C.
gave no cycloisomerized product.18 Intrigued by these results, we sought to determine if an electron poor alkene was essential for the transformation. We prepared acetamide 1p, which can cyclize with the tethered methallyl group to generate the respective indoline. Subjecting 1p to the standard reaction conditions gave 2p in excellent yield (93% yield). In addition, replacing the acetyl group with a tosyl group also afforded the product in good yield (2q, 89% yield).17 These findings suggest that an oxygen atom may serve as a directing group to facilitate the oxidative addition step.19 Exploiting the directed oxidative addition, tetrahydroquinoline 2r was obtained in 65% yield. Aryl bromides are cheaper, more readily available, and easily accessible building blocks in comparison to the corresponding aryl iodides. However, with this methodology, the generation of the alkyl bromide from bromoacrylamide 3a proceeded in low yield.20 We anticipated that in the presence of an external iodide source, a halogen exchange would occur in situ to generate the respective alkyl iodide (Scheme 5). Upon adding 2 equivalents of potassium iodide to the standard reaction conditions, 2a was formed in 83% yield starting from 3a. By using the second set of optimized conditions, the electron-rich p-methoxybromoacrylamide 3b cyclized to give the corresponding oxindole 2s in 70% yield. Additionally, the dioxol bearing oxindole 2t was generated in good yield (84% yield). Analogous to the generation of 2j, the formation of the Nbenzylated oxindole 2u required longer reaction times (44% yield). To further showcase the benefits of employing nickel in carboiodination, the enantioselective variant was explored (Scheme 6). A variety of ligands were screened including bisphosphines and BINOL-derived chiral phosphites and phosphoramidites. Within the class of these ligands, limited
*
Reactions were run on 0.2 mmol scale. Isolated yields. e.r. values were determined by HPLC analysis on a chiral stationary phase.
success was found in achieving high enantioselectivity, with MonoPhos providing the best yield and e.r. (45% yield and 65:35 e.r.).21 Serendipitously, we discovered that using a dual ligand system was essential in achieving higher enantioselectivity.22 Utilizing a 9:1 mixture of (S)-TolBINAP:(S)-BINAPO afforded the model substrate 2a in 50% yield and 89:11 e.r.23 Employing a more electron rich acrylamide 1c gave 2c in higher yield and good e.r. (57% yield, 89:11 e.r.). In contrast to the racemic variant that required elevated temperature and longer reaction time, generation of the trifluoromethylated oxindole 2f proceeded in good yields and moderate e.r. (84% yield, 78:22 e.r.). Switching the vinyl aromatic group to an alkyl group gave moderate yields and lower e.r. (65:35 e.r.). We propose that the reaction proceeds via an enantioselective oxidative addition3c,24 or carbometalation. A radical pathway is unlikely but cannot be ruled out.25 Efforts are underway to understand the origin of this two ligand effect. In conclusion, we have reported the first nickel-catalyzed cycloisomerization reaction involving the regeneration of a valuable carbon−halogen bond. Two sets of reaction conditions were found to promote this transformation. Diverse functional groups were tolerated and the resulting oxindoles were obtained in good to excellent yields. Additionally, the Nicatalyzed halogen-exchange carboiodination reaction is also reported. An enantioselective variant was identified employing a dual ligand system to attain good e.r. 10952
DOI: 10.1021/jacs.8b06966 J. Am. Chem. Soc. 2018, 140, 10950−10954
Communication
Journal of the American Chemical Society
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N.; Wen, J.; Tcyrulnikov, S.; Biswas, S.; Qu, B.; Hie, L.; Kurouski, D.; Wu, L.; Grinberg, N.; Haddad, N.; Busacca, C. A.; Yee, N. K.; Song, J. J.; Garg, N. K.; Zhang, X.; Kozlowski, M. C.; Senanayake, C. H. Org. Lett. 2017, 19, 3338. (m) Qin, X.; Lee, M. W. Y.; Zhou, J. S. Angew. Chem., Int. Ed. 2017, 56, 12723. (n) Yu, P.; Morandi, B. Angew. Chem., Int. Ed. 2017, 56, 15693. (o) Li, Y.; Wang, K.; Ping, Y.; Wang, Y.; Kong, W. Org. Lett. 2018, 20, 921. (p) Lu, K.; Han, X.-W.; Yao, W.W.; Luan, Y.-X.; Wang, Y.-X.; Chen, H.; Xu, X.-T.; Zhang, K.; Ye, M. ACS Catal. 2018, 8, 3913. (q) Yen, A.; Lautens, M. Org. Lett. 2018, 20, 4323. (4) For selected examples relevant to this work, see: (a) Higgs, A. T.; Zinn, P. J.; Simmons, S. J.; Sanford, M. S. Organometallics 2009, 28, 6142. (b) Renz, A. L.; Pérez, L. M.; Hall, M. B. Organometallics 2011, 30, 6365. (c) Zheng, B.; Tang, F.; Luo, J.; Schultz, J. W.; Rath, N. P.; Mirica, L. M. J. Am. Chem. Soc. 2014, 136, 6499. (d) Lee, H.; Börgel, J.; Ritter, T. Angew. Chem., Int. Ed. 2017, 56, 6966. (e) Diccianni, J. B.; Hu, C.; Diao, T. Angew. Chem., Int. Ed. 2017, 56, 3635. (f) Haines, B. E.; Yu, J.-Q.; Musaev, D. G. Chem. Sci. 2018, 9, 1144. (5) For selected reviews and references therein, see: (a) Yamamoto, Y. Chem. Rev. 2012, 112, 4736. (b) Chen, F.; Wang, T.; Jiao, N. Chem. Rev. 2014, 114, 8613. (6) Watson, M. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 12594. (7) Nakao, Y.; Ebata, S.; Yada, A.; Hiyama, T.; Ikawa, M.; Ogoshi, S. J. Am. Chem. Soc. 2008, 130, 12874. (8) For selected reviews and references therein on bioactive molecules, see: (a) Hernandes, M. Z.; Cavalcanti, S. M. T.; Moreira, D. R. M.; de Azevedo, W. F., Jr.; Leite, A. C. L. Curr. Drug Targets 2010, 11, 303. (b) Kosjek, T.; Heath, E. Halogenated Heterocycles as Pharmaceuticals: In Halogenated Heterocycles: Synthesis, Application and Environment; Iskra, J., Ed.; Springer: New York, 2012. (c) Wilcken, R.; Zimmermann, M. O.; Lange, A.; Joerger, A. C.; Boeckler, F. M. J. Med. Chem. 2013, 56, 1363. (9) For selected reviews and references therein for halogenated natural products, see: (a) Gribble, G. D. Acc. Chem. Res. 1998, 31, 141. (b) Gribble, G. W. Structure and Biosynthesis of Halogenated Alkaloids. In Modern Alkaloids: Structure, Isolation, Synthesis, and Biology; Fattorusso, E., Tagilialatela-Scafati, O., Eds.; Wiley-VCH: Weinheim, 2008. (10) For selected reviews and references therein, see: (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (b) Late Transition Metal-Mediated Formation of Carbon−Halogen Bonds. In C-X Bond Formation; Vigalok, A., Kaspi, A. W., Eds.; Springer: Berlin, Heidelberg, 2010. (c) Campbell, M. G.; Ritter, T. Chem. Rev. 2015, 115, 612. (d) Petrone, D. A.; Ye, J.; Lautens, M. Chem. Rev. 2016, 116, 8003. (e) Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advancements. In New Trends in Cross-Coupling: Theory and Applications; Colacot, T. J., Ed.; Royal Society of Chemistry: Cambridge, 2015. (11) (a) Newman, S. G.; Lautens, M. J. Am. Chem. Soc. 2010, 132, 11416. (b) Newman, S. G.; Lautens, M. J. Am. Chem. Soc. 2011, 133, 1778. (12) Liu, H.; Li, C.; Qiu, D.; Tong, X. J. Am. Chem. Soc. 2011, 133, 6187. (13) For selected examples, see: (a) Hao, W.; Wei, J.; Geng, W.; Zhang, W.-X.; Xi, Z. Angew. Chem., Int. Ed. 2014, 53, 14533. (b) Chu, L.; Xiao, K.-J.; Yu, J.-Q. Science 2014, 346, 451. (c) Chen, C.; Hu, J.; Su, J.; Tong, X. Tetrahedron Lett. 2014, 55, 3229. (d) Chen, C.; Hou, L.; Cheng, M.; Su, J.; Tong, X. Angew. Chem., Int. Ed. 2015, 54, 3092. (e) Zhu, R.-Y.; Liu, L.-Y.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 12394. (f) Ratushnyy, M.; Parasram, M.; Wang, Y.; Gevorgyan, V. Angew. Chem., Int. Ed. 2018, 57, 2712. (g) Kinney, R. G.; Tjutrins, J.; Torres, G. M.; Liu, N. J.; Kulkarni, O.; Arndtsen, B. A. Nat. Chem. 2018, 10, 193. (14) For selected examples, see: (a) Quesnel, J. S.; Arndtsen, B. A. J. Am. Chem. Soc. 2013, 135, 16841. (b) Le, C. M.; Menzies, P. J. C.; Petrone, D. A.; Lautens, M. Angew. Chem., Int. Ed. 2015, 54, 254. (c) Quesnel, J. S.; Kayser, L. V.; Fabrikant, A.; Arndtsen, B. A. Chem. -
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.8b06966. X-ray data for 2a (CIF) Experimental procedures, optimization, characterization and X-ray data (PDF)
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AUTHOR INFORMATION
Corresponding Author
*
[email protected] ORCID
Hyung Yoon: 0000-0003-4573-2160 Mark Lautens: 0000-0002-0179-2914 Author Contributions †
H.Y. and A.D.M. contributed equally to this work.
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the University of Toronto, Alphora Research, Inc., and the Natural Sciences and Engineering Research Council (NSERC) for financial support. H.Y. is the recipient of an Ontario Graduate Scholarship. We thank Dr. I. Franzoni (University of Toronto), Y.J. Jang (University of Toronto) and Professor Sophie Rousseaux (University of Toronto) for insightful discussion throughout the project. Y. J. Jang and E. Larin (University of Toronto) are thanked for the preparation of starting materials 3c, 3d. We thank Dr. Alan Lough (University of Toronto) for single-crystal X-ray analysis of 2a.
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REFERENCES
(1) For selected reviews and references therein, see: (a) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346. (b) Han, F.-S. Chem. Soc. Rev. 2013, 42, 5270. (c) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature 2014, 509, 299. (d) Gu, J.; Wang, X.; Xue, W.; Gong, H. Org. Chem. Front. 2015, 2, 1411. (e) Wang, X.; Dai, Y.; Gong, H. Top Curr. Chem. 2016, 374, 43. (f) Richmond, E.; Moran, J. Synthesis 2018, 50, 499. (g) Lucas, E. L.; Jarvo, E. R. Nat. Rev. Chem. 2017, 1, 0065. (2) For selected reviews and references therein, see: (a) Phapale, V. B.; Cárdenas, D. J. Chem. Soc. Rev. 2009, 38, 1598. (b) Han, F.-S. Chem. Soc. Rev. 2013, 42, 5270. (c) Pellissier, H. Enantioselective Nickel-Catalyzed Cross-Coupling Reactions. In Enantioselective NickelCatalyzed Transformations; Hardacre, C., Gebbink, B. K., Rodriguez, J., Eds.; Royal Society of Chemistry: Cambridge, 2016. (3) For selected cross-coupling examples relevant to this work, see: (a) Matsubara, R.; Jamison, T. F. J. Am. Chem. Soc. 2010, 132, 6880. (b) Matsubara, R.; Gutierrez, A. C.; Jamison, T. F. J. Am. Chem. Soc. 2011, 133, 19020. (c) Gøgsig, T. M.; Kleimark, J.; Nilsson Lill, S. O.; Korsager, S.; Lindhardt, A. T.; Norrby, P.-O.; Skrydstrup, T. J. Am. Chem. Soc. 2012, 134, 443. (d) Ehle, A. R.; Zhou, Q.; Watson, M. P. Org. Lett. 2012, 14, 1202. (e) Standley, E. A.; Jamison, T. F. J. Am. Chem. Soc. 2013, 135, 1585. (f) Harris, M. R.; Konev, M. O.; Jarvo, E. R. J. Am. Chem. Soc. 2014, 136, 7825. (g) Tasker, S. Z.; Gutierrez, A. C.; Jamison, T. F. Angew. Chem., Int. Ed. 2014, 53, 1858. (h) Desrosiers, J.-N.; Hie, L.; Biswas, S.; Zatolochnaya, O. V.; Rodriguez, S.; Lee, H.; Grinberg, N.; Haddad, N.; Yee, N. K.; Garg, N. K.; Senanayake, C. H. Angew. Chem., Int. Ed. 2016, 55, 11921. (i) Fang, X.; Yu, P.; Morandi, B. Science 2016, 351, 832. (j) Vandavasi, J. K.; Hua, X. Y.; Halima, H. B.; Newman, S. G. Angew. Chem., Int. Ed. 2017, 56, 15441. (k) Medina, J. M.; Moreno, J.; Racine, S.; Du, S.; Garg, N. K. Angew. Chem., Int. Ed. 2017, 56, 6567. (l) Desrosiers, J.10953
DOI: 10.1021/jacs.8b06966 J. Am. Chem. Soc. 2018, 140, 10950−10954
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Journal of the American Chemical Society Eur. J. 2015, 21, 9550. (d) Le, C. M.; Hou, X.; Sperger, T.; Schoenebeck, F.; Lautens, M. Angew. Chem., Int. Ed. 2015, 54, 15897. (e) Le, C. M.; Sperger, T.; Fu, R.; Hou, X.; Lim, Y. H.; Schoenebeck, F.; Lautens, M. J. Am. Chem. Soc. 2016, 138, 14441. (f) Malapit, C. A.; Ichiishi, N.; Sanford, M. S. Org. Lett. 2017, 19, 4142. (g) Zhu, R.-Y.; Saint-Denis, T. G.; Shao, Y.; He, J.; Sieber, J. D.; Senanayake, C. H.; Yu, J.-Q. J. Am. Chem. Soc. 2017, 139, 5724. (15) (a) Newman, S. G.; Howell, J. K.; Nicolaus, N.; Lautens, M. J. Am. Chem. Soc. 2011, 133, 14916. (b) Petrone, D. A.; Malik, H. A.; Clemenceau, A.; Lautens, M. Org. Lett. 2012, 14, 4806. (c) Petrone, D. A.; Yoon, H.; Weinstabl, H.; Lautens, M. Angew. Chem., Int. Ed. 2014, 53, 7908. (16) Petrone, D. A.; Franzoni, I.; Ye, J.; Rodriguez, J. F.; PobladorBahamonde, A. I.; Lautens, M. J. Am. Chem. Soc. 2017, 139, 3546. (17) Acrylamide 1a was subjected to the equivalent Pd-catalyzed cyclization outlined by Newman and Lautens to give 2a in 93% yield (see reference 11b). Replacing NiI2(PPh3)2 with Pd(PPh3)4 provided 2a in
