Subscriber access provided by FONDREN LIBRARY, RICE UNIVERSITY
Letter
Developing NHC-Iridium Catalysts for the Highly Efficient Enantioselective Intramolecular Hydroamination Reaction Pengchao Gao, Gellért Sipos, Daven Foster, and Reto Dorta ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b02508 • Publication Date (Web): 09 Aug 2017 Downloaded from http://pubs.acs.org on August 9, 2017
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 free 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 accessible to all readers and 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.
ACS Catalysis 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 5
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
Developing NHC-Iridium Catalysts for the Highly Efficient Enantioselective Intramolecular Hydroamination Reaction. Pengchao Gao, Gellért Sipos, Daven Foster, Reto Dorta* Department of Chemistry, School of Molecular Sciences, University of Western Australia, 35 Stirling Highway, 6009 Perth, Australia. Supporting Information Placeholder ABSTRACT: Chiral, cationic NHC-iridium complexes
are introduced as catalysts for the intramolecular hydroamination reaction of unactivated aminoalkenes. The catalysts show high activity in the construction of pyrrolidines, which are accessed with excellent optical purity. Enantiomerically enriched piperidines and indolines are also produced and various functional groups are tolerated with this LTM system. A reaction mechanism is proposed and a major deactivation pathway of these catalysts is presented and discussed. KEYWORDS: chiral NHC, iridium, catalysis, hydroamination, N-heterocycles
Optically active N-heterocyclic compounds are of prime importance in commodity and specialty chemicals and are often present in natural products and medicines. One of the most elegant ways of producing compounds such as chiral pyrrolidines, piperidines or indolines is through the use of an enantioselective olefin hydroamination reaction starting from the appropriate aminoolefin precursor molecules.1 Classical hydroamination (HA) reactions that employ electronically unbiased olefins and alkenes are also an illustration of perfect atom economy in chemical reactions, and although great progress has been achieved over the last two decades, they are far from well established. Advances since Marks' and coworkers first reports of asymmetric intramolecular HA reactions,2 have by and large concentrated on developing the original rare-earth systems, alkali and alkaline earth metal catalysts as well as early-transition metal compounds.1 Impressive recent results by the groups of Schafer,3b and Sadow,3c-f have indeed shown that chiral zirconium catalysts are able to provide pyrrolidine products with high enantiopurity and represent the current state of the art for these asymmetric transformations. The major drawback that remains with these catalyst systems is their highly sensitive nature and very limited functional group tolerance that impedes a broader implementation of this elegant synthetic methodology.
Late-transition metal (LTM) catalysts would without doubt alleviate the problem, but the asymmetric intramolecular HA reaction of unactivated aminoolefins has until now not been developed to any degree,4 with a single report existing in the literature, in which Buchwald et al. use a cationic rhodium systems with chiral MOP-type ligands.5 In this context, we were inspired by results reported by Stradiotto et al. who have applied the dimeric [Ir(COD)Cl]2 complex as a precatalyst in the non-chiral version of this reaction.6 We were able to show that by replacing the halide with NHC structures featuring appropriately substituted naphthyl wingtips,7 highly unsaturated, yet stable cationic [(NHC)Ir(COD)]+ species can be isolated that display greatly improved activities in the intramolecular HA reaction (NHC = 2,7-SICyNap, Scheme 1, top left).8 Unfortunately, a first foray into using an enantiopure NHC ligand led to highly attenuated catalyst activities and prevented an extended study. Previous work (2016) Cy
This work Cy Ph
[PF 6] N
Cy
N
N
Cy Cy
Ph
Cy
Ph [BF 4]
Cy
Cy Cy
N
a)
N
(Ra,Ra,S,S)-1 (ca. 85% dr)
Ph
Cy Ph
Cy N
N
Cy Ir
H Cy
a) 0.5 [Ir(COD)Cl] 2,
N
activity in HA? selectivity in HA?
racemic, high activity in HA
N
[X]
Cy
Ir Cy
Ir Cy
Ph
Ph
Cy Cl
(Ra,Ra,S,S)-2 (optically pure) NaO tBu,
b)
Cy
Ph N
[X]
Cy
Ir Cy
[(Ra,Ra,S,S)-3][X]
THF, work-up. b) Ag[X] or Na[X], CH 2Cl 2, work-up.
Scheme 1. Catalyst structures and synthesis of cationic 3[X] complexes. Results herein report the preparation of optically pure [(NHC)Ir(COD)]+ catalysts that combine the high activity of [(2,7-SICyNap)Ir(COD)]+ discussed above with excellent enantioselectivities in this HA reaction. Following
ACS Paragon Plus Environment
3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
7 3
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
earlier studies from our group,9 we installed enantiomerically pure (S,S)-diphenyldiamine into the NHC backbone in order to access the optically enriched (Ra,Ra)-isomer of the ligand salt (ca. 85% dr) containing the same unsymmetrically substituted 2,7-dicyclohexyl-1-naphthyl wingtips mentioned above.10 This NHC salt (DiPh-2,7-SICyNap, 1) was then used in the synthesis of neutral complex 2, at which stage the minor stereoisomers of the NHC [(Ra,Sa),S,S)-1] and [(Sa,Sa),S,S)-1] were conveniently eliminated upon purification. Finally, salt metathesis with AgPF6, NaBArF24 or AgNTf2 gave access to three cationic complexes (3[X]). All of these cationic, formally 14-electron complexes show a stabilizing interaction via one of the naphthyl groups, leading to tilting of the NHC structure as discussed elsewhere.8
Barf conversion
NTf2 time
NTf2 conversion
0 55.83111851 60.79627003 63.58075725 65.80910266 69.59557531 77.53275193 83.52654873 87.95734928 91.27728817
0 4.766666667 5.1 5.3 5.983333333 6.75 120 7.4 8.233333333 9.166666667 10010.33333333
0 78.32570398 79.06820076 80.57924391 85.01749523 88.1808217 90.1475897 92.50034578 94.60800175 96.20873151
93.54980299 95.50778665 96.81845654 97.66737339
8013.81666667
11.48333333 12.65
97.50094267 98.17554048 98.56736767 99.26774923
98.29649654 98.91938485 99.11346249 99.47889486 99.59625425 100.003853 99.85970324 100.1649695 100.160294 100.6126928 100.0574044 100.1214843 100.2633799 100.3755176 100.3967997 100.129941 100.2778073 100.4272886 100.2245399 100.5042448 100.3718746 100.4816715 100.2671216 100.6978575 100.4216775 100.4518396 100.6576661 100.1179201 100.4594082 100.4752696 100.4741928 100.499831 100.4856859 100.4225414 100.4958258 100.3882273 100.2345559 100.4734924 100.3039655 100.48331 100.3438348 100.4906544 100.4022753 100.4962449 100.4041677 100.4464267 100.4622274 100.5230772 100.6106597 100.1439108 100.5772129 100.0886774 100.4918853 100.4546352
conversion (%)
0 5 3 3 3 3 6 3 5 7
ACS Catalysis
14.98333333 16.15 6017.31666667 18.48333333 19.65 4020.81666667 21.98333333 23.15 2024.31666667 25.48333333 26.65 027.81666667 28.98333333 0 30.15 5 31.31666667 32.48333333 33.65 34.81666667 35.98333333 37.15 38.31666667 39.48333333 40.65 41.81666667 42.98333333 44.15 45.31666667 46.48333333 47.65 48.81666667 49.98333333 51.15 52.31666667 53.48333333 54.65 55.81666667 56.98333333 58.15 59.31666667
10
15
99.54502557 99.73746945 99.89769107 100.1377007 100.0988756 100.0044478 100.410035 100.4152356 100.2506957 100.4181872 100.2729364 100.2963801 20 25 30 100.3223066 time (min) 100.3821335 100.4795206 100.1304349 100.3724104 100.1070585 100.1247415 100.5025573 100.1262839 100.4844963 100.1554894 100.2781063 100.3620261 100.171969 100.0846181 99.99820492 100.1671606 100.2474451 100.1657137 100.3572049 100.0369519 100.0977438 100.2835889 100.2740009 100.0769642 100.0568277
100
3, R = Bn 10, R = p -NO2Ph
Page 2 of 5
below (Table 1). Entry 4 shows that a switch to an alternative solvent (tBuOH) also provides good results, but reactions in that case had to be run at slightly
Table 1: Scope of the intramolecular HA with 3[X].
Entry: Product
3[X]/mol%
Solvent
kobsa
(Conv.)/ yield(%)b
ee(%)c
c
1: 4b R=H 2: 4b R=H 3: 4b R=H 4: 4b R=H 5: 5b R=4-NO2 6: 6b R=4-Cl 7: 7b R=4-MeO 8: 8b R=4-CO2Me 9: 9b R=2-Me
3[NTf2]/1 3[BArF24]/1 3[PF6]/1 3[BArF24]/1 3[NTf2]/2 3[NTf2]/2 3[NTf2]/2 3[NTf2]/2 3[NTf2]/2
CD2Cl2 CD2Cl2 CD2Cl2 t BuOH CD2Cl2 CD2Cl2 CD2Cl2 CD2Cl2 CD2Cl2
31 25 8 20 92 49 53 25
(99)/95 (99)/93 (99)/96 94 (99)/92 (99)/91 (99)/95 (99)/94 (99)/91
>99 97 99 97 98 97 98 >99 >99
10: 10b R=CH2Cy 11: 11b R=Me
3[NTf2]/2 3[NTf2]/2
CD2Cl2 CD2Cl2
9 -d
(99)/92 (99)/89
99 90
12: 12b
3[NTf2]/2
CD2Cl2
2.2
(99)/96
97
13: 13b R=H 14: 14b R=MeO
3[NTf2]/2 3[NTf2]/2
CD2Cl2 CD2Cl2
15 1.7
(99)/93 (99)/96
99 96
15: 15b
3[NTf2]/5
CD2Cl2
30 d
(89)/81
98
16: 16b
3[NTf2]/2
CD2Cl2
12
(99)/95
>99
17: 17b R=H 18: 18b R=MeO
3[NTf2]/2 3[NTf2]/2
CD2Cl2 CD2Cl2
2.0 1.5
(99)/95 (92)/88
98 96
19: 19b R=H 20: 20b R=Br
3[NTf2]/2 3[NTf2]/2
CD2Cl2 CD2Cl2
68 75
(99)/93 e (99)/92 (1:1)ge (1:1)g
97/99 99/99
21: 21b R=H 22: 22b R=Br
3[BArF24]/5 3[NTf2]/5
CD2Cl2 CD2Cl2
18 7
(99)/90 e (99)/93 e
94/77 96/76
23: 23b
3[NTf2]/2
CD2Cl2
3.3
(99)/94 e
86/63
24: 24b
3[BArF24]/5
t
BuOH
-
93
87
25: 25b
3[BArF24]/7
t
BuOH
-
88
62
11, R = p -ClPh 12, R = p -MeOPh 13, R = o -MePh 18, R = -CH2Cy
3[PF6]
20, R = Ph
3[BArF24] 3[NTf2]
35
40
45
50
Figure 1. Plots of the conversion (%) vs time (min) for 4a (left) and plots of ln([4a]/[4a]0) vs time (min) (right).
The different anions were chosen in order to study the influence of the gegenion on the catalytic activity of these NHC-iridium species.11 Figure 1 presents the outcome of this catalyst comparison as applied to the standard HA substrate N-benzyl-2,2-diphenylpent-4-en-1-amine (4a). Gratifyingly, all three catalysts showed excellent activities with full conversion achieved within one hour at room temperature employing comparatively low catalyst loadings for this challenging transformation (1 mol%). This corresponds to approximate TOF50 values of 377 h-1 {3[PF6]}, 1071 h-1 for {3[BArF24]} and 1500 h-1 for {3[NTf2]}, placing these catalysts on par or above the most active HA catalysts reported (rare-earth systems).2,3a,d Enantioselectivities were equally satisfying and showed a slight dependence on the counteranion used, with 3[BArF24] providing marginally lower enantioselectivity (97% ee) than 3[PF6] (98.5% ee) and 3[NTf2] (99.5% ee). What came as a surprise was the fact that 3[NTf2] produced the most active system in this comparison. As far as we are aware, there is not a single report in the literature using a cationic iridium complex with an NTf2 counteranion in catalysis.12,13 With these results in hand, we moved ahead and started a broader investigation into the substrate scope using both 3[BArF24] and 3[NTf2] catalysts and results are tabulated
ACS Paragon Plus Environment
Page 3 of 5
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
t 26: 26b 3[NTf2]/2 BuOH 92 94 27: 26b 3[NTf2]/5 CD2Cl2 0.7 (99)/91 90 a (10-2 min-1); pseudo-first-order rate constants, see SI for details. b Isolated yield. c Ee’s determined by HPLC, by 1H NMR of (R)-(−)-O-acetyl-mandelic acid derivatives or by 19F NMR of Mosher amide derivatives. Absolute stereochemistry: (S) as deduced by comparison (4b, 9b, 19b, 20b). d kobs not given for 11 (reaction too fast); kobs only indicative for 15, see SI for details. e Diastereomeric ratios: 1.1:1 (19b, 20b), 3:4 (21b), 1:1 (22b), 3:2 (23b). Isolated yields are for the mixture of diastereomers.
elevated temperature to ensure appropriate dissolution of the reaction mixture. Entries 5-11 highlight the fact that contrary to what had been recorded for rhodium,6 the present system is relatively insensitive to variations of the nitrogen substituent. Different benzyl substitutions (entries 5-8), including ones that contain functional groups not tolerated by early-transition/lanthanide catalysts, uniformly lead to excellent results both in terms of reactivity and selectivity. Among the para-modified benzyl groups tested, we do not see any apparent trend between reactivity (kobs) and their electronic nature. Replacing these benzyl groups with purely aliphatic substituents is equally successful (entries 10,11), although a slight erosion in enantioselectivity can be seen for the methyl substituted substrate 11a. This might indicate that a more sterically encumbered N-substituent (entries 1-10) is beneficial for selectivity and is recognized by the catalyst structure. This is in line with the observation that the similarly sized N-phenyl substituent does not provide the corresponding product in optically enriched form (92% yield, 9% ee, see SI).14 3,3’-Substituted spirocyclic pyrrolidine products were accessed next and entries 12-16 show that here again, excellent reactivity produces the product molecules in very high optical purity. Noteworthy is the fact that the tosylprotected substrate in entry 16 is perfectly amenable to undergo cyclization, again highlighting the functional group tolerance of the present LTM system. Unsymmetrically 2,2’-disubstituted substrates (entries 19,20) underwent cyclization to give diastereomer mixtures in approximately equal amount and with excellent enantioselectivity. Kinetic resolution was also not observed in the case of racemic N-benzyl-2-phenyl-4-pentenamine or N-benzyl2-isopropyl-4-pentenamine (entries 21-23), again giving rise to diastereomer mixtures in roughly equal amounts. Not surprisingly, reactivity was lower in these cases, but reactions could still be run at room temperature giving high yields of isolated product. The enantioselectivity of one of the diastereomers was consistently higher than that of the other. The most straightforward explanation of these results would see a scenario where the backbone substrate substitution is recognized by the catalyst structure, and where omitting it (H instead of R) would lead to a certain loss of enantioselection due to a less ordered transition state. Gratifyingly, a 2,2’-difluoro substituted aminoalkene (24a, entry 24) was also amenable to cyclization to give the corresponding fluorinated pyrrolidine product in high
yield and optical purity (93% yield, 87% ee). Such partially fluorinated pyrrolidines are of central importance in drug development,15 and our results show how the asymmetric HA reaction might be used for accessing this family of compounds. Unfortunately, replacing the fluorine atoms by hydrogens and trying to ring-close the parent Nbenzyl-pent-4-en-1-amine was not successful. While the intramolecular HA reaction did occur under forcing conditions (80 °C, 5 mol% cat.) to give acceptable yields of product (69%), the enantioselectivity of the transformation was negligible (20% ee). On the other hand, intramolecular HA to access an indoline derivative (26b) proceeded remarkably well and gave the product with excellent enantioselectivity and in high isolated yield (entries 26/27). Furthermore, a representative piperidine was also obtained with reasonable optical purity when employing a higher catalyst loading (entry 25). Ph N
Naph
NHR
Ph N
[X] Naph NHR
Ir Ph Naph N
Ph
A
Ph [X]
Naph
N
Ph
N
N Naph RHN
Naph Ir
Ir Ph
3[X]
N
Naph RN
[X]
Ph [X] N Ir
B
Naph R N
C OH 3[NTf 2] (5 mol%)
H 2N
H N
+
O
tBuOH,
60°C 0.6 M
1.5 equiv
0.3 mmol
N
96% yield, 74% ee
D
Bn
D Cl [NTf ] 2 N
Br
Bn
Br 22b [NTf 2]
Cy Ph
N Cy
Ph N
Cy
Cl
Cl
D
D
Ph
Ph
Cy
Cy N
N Cy
Ir Cy
3[NTf 2]
Ir
Cy Cl
2 (not active in HA)
Scheme 2. Proposed catalytic cycle (above), example of a ring-opening amination of oxabicycles catalyzed by 3[NTf2] (middle) and catalyst decomposition in CD2Cl2 as observed for entry 22 of Table 1. The proposed reaction mechanism is drawn in Scheme 2 (top) and involves coordination of the olefin (A) followed by external attack of the amine to give the neutral complex B before hydrogen migration generates cationic C that would regenerate 3[X] after liberation of the product.16 Overall, it would therefore follow a similar pathway to Hartwig’s cationic rhodium systems,5d,e and be distinctly different from the reaction mechanism proposed
ACS Paragon Plus Environment
ACS Catalysis
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
for asymmetric HA reactions between norbornene and aniline using electron-rich, neutral iridium catalysts.17 Our postulated mechanism is in line with several observations: 1) liberation of COD (or its hydrogenated derivatives) or hydride formation could not be observed at any point during these conversion runs; 2) catalyst 3[X] is relatively insensitive to the electronic nature of the N-substituent;18 3) the overall electronic structure of 3[X] (cationic complex, COD ligand) disfavors a classical N-H oxidative addition / insertion / reductive elimination pathway; 4) a mechanistically related reaction that relies on such an external attack of the amine (asymmetric ringopening amination of oxabicycles),19 can be performed successfully under absolutely identical reaction conditions (Scheme 2, middle). For some of the more challenging reaction runs, NMR analysis of the mixture at the end of the catalytic run revealed that part of the catalyst had transformed back to the neutral, catalytically inactive (NHC)Ir(COD)Cl (2) precursor as evidenced by the appearance of diagnostic signals in 1H NMR as well as 13C NMR (see SI for details). Complex 2 in fact arises from the reaction of the pyrrolidine product with the methylene chloride solvent (Scheme 2, bottom). This type of nucleophilic substitution reaction (Menshutkin reaction) is generally very slow (half-life for trimethylamine and CH2Cl2 of a month),20 but seems to be greatly facilitated by the presence of the cationic [(NHC)Ir(COD)]+ species.21 The resulting ammonium salt was identified via high resolution mass spectrometry. The generation of neutral chloro complex 2 during catalysis unfortunately also leads to product contamination as it cannot be separated and removed efficiently during workup and column chromatographic purification of the product. After unsuccessfully applying a literature procedure used for removal of Grubbs-type ruthenium catalyst contaminants,22 we developed a protocol where the cationic iridium complex is reformed and separated by extracting the product into a non-polar solvent at the beginning of the purification procedure (see SI for details).23 Two decades after Togni et al. had shown that neutral iridium catalysts effect the asymmetric hydroamination between norbornene and aniline,24 we herein report a cationic iridium system that is able to cyclize unactivated aminoalkenes with unprecedented ease to give optically enriched pyrrolidine, piperidine and indoline products. The present system achieves this by using a chiral, monodentate NHC ligand and by incorporating the NTf2 anion, yielding a catalyst that easily matches and exceeds results obtained with the latest reference zirconium systems and at the same time overcomes their lack of functional group tolerance. The catalyst platform disclosed here will serve as a basis for our continued efforts into expanding the utility of such chiral NHC ligands and pertinent developments will be discussed in due course.
Page 4 of 5
Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Experimental procedures, characterization of compounds (PDF).
AUTHOR INFORMATION Corresponding Author
*
[email protected] Funding Sources
No competing financial interests have been declared.
ACKNOWLEDGMENT R.D. thanks the Australian Research Council for generous funding (FT130101713). P.G. and G.S. thank UWA for International Postgraduate Research Scholarships. D.F. thanks UWA for an RTP scholarship.
REFERENCES (1) For selected reviews on the HA reaction: (a) Müller, T. E.; K. C. Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108, 3795. (b) Hannedouche, J.; Schulz, E. Chem. Eur. J. 2013, 19, 4972. (c) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J. Chem. Rev. 2015, 115, 2596. (d) Bernoud, E.; Lepori, C.; Mellah, M.; Schulz, E.; Hannedouche, J. Catal. Sci. Technol. 2015, 5, 2017. (2) (a) Gagné, M. R.; Brard, L.; Conticello, V.; Giardello, M. A.; Stern, C. L.; Marks, T. J. Organometallics 1992, 11, 2003. (b) Conticello, V. P.; Brard, L.; Giardello, M. A.; Tsuji, Y.; Sabat, M.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 2761. (c) Giardello, M. A.; Conticello, V. P.; Brard, L.; Gagné, M. R.; Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10241. (3) For catalytic systems providing >90 % ee for at least two pyrrolidine-type products; with rare-earth/group 4 metals, see: (a) Gribkov, D. V.; Hultzsch, K. C.; Hampel, F. J. Am. Chem. Soc. 2006, 128, 3748. (b) Wood, M. C.; Leitch, D. C.; Yeung, C. S.; Kozak, J. A.; Schafer, L. L. Angew. Chem. Int. Ed. 2007, 46, 354. (c) Manna, K.; Xu, S.; Sadow, A. D. Angew. Chem. Int. Ed. 2011, 50, 1865. (d) Manna, K.; Kruse, M. L.; Sadow, A. D. ACS Catal. 2011, 1, 1637. (e) Manna, K.; Everett, W. C.; Schoendorf, G.; Ellern, A.; Windus, T. L.; Sadow, A. D. J. Am. Chem. Soc. 2013, 135, 7235. (f) Manna, K.; Eedugurala, N.; Sadow, A. D. J. Am. Chem. Soc. 2015, 137, 425. (g) Zhou, X.; Wei, B.; Sun, X.L.; Tang, Y.; Xie, Z. Chem. Commun. 2015, 51, 5751. With Mg, see: (h) Zhang, X.; Emge, T. J.; Hultzsch, K. C. Angew. Chem. Int. Ed. 2012, 51, 394. (4) Other LTM systems need to use either electronically activated amines and/or activated olefins (see ref [1c]). Most noteworthy recent developments have introduced formal HA reactions using electronpoor amines and an additional exogenous hydrogen source that are mediated by chiral Cu catalysts. For first reports: (a) Miki, Y.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem. Int. Ed. 2013, 52, 10830. (b) S. Zhu, S.; Niljianskul, N.; Buchwald, S. L. J. Am. Chem. Soc. 2013, 135, 15746. For a first example of an asymmetric intramolecular HA reaction with this system, see: (c) Wang, H.; Yang, J. C.; Buchwald, S. L. J. Am. Chem. Soc. 2017, 139, 8428. For an overview: (d) Pirnot, M. T.; Wang, Y.-M.; Buchwald, S. L. Angew. Chem. Int. Ed. 2016, 55, 48. (5) (a) Shen, X.; Buchwald, S. L. Angew. Chem. Int. Ed. 2010, 49, 564. For reaction development and mechanistic insights of non-chiral cationic rhodium systems, see: (b) Takemiya, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 6042. (c) Liu, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 1570. (d) Julian, L. D.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 13813. (e) Liu, Z.; Yamamichi, H.; Madrahimov, S. T.; Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 2772. (6) (a) Hesp, K. D.; Stradiotto, M. Org. Lett. 2009, 11, 1449. (b) Hesp, K. D.; Tobisch, S.; Stradiotto, M. J. Am. Chem. Soc. 2010, 132, 413.
ASSOCIATED CONTENT ACS Paragon Plus Environment
Page 5 of 5
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
(7) For examples that feature non-chiral NHCs within chelates: (a) Bauer, E. B.; Andavan, G. T. S.; Hollis, T. K.; Rubio, R. J.; Cho, J.; Kuchenbeiser, G. R.; Helgert, T. R.; Letko, C. S.; Tham, F. S. Org. Lett. 2008, 10, 1175. (b) Specht, Z. G.; Cortes-Llamas, S. A.; Tran, H. N.; Van Niekerk, C. J.; Rancudo, C. J.; Golen, J. A.; Moore, C. E.; Rheingold, A. L.; Dwyer, T. J.; Grotjahn, D. B. Chem. Eur. J. 2011, 17, 6606. (c) Zhang, R.; Xu, Q.; Mei, L. Y.; Li, S. K.; Shi, M. Tetrahedron 2012, 68, 3172. For an Au-catalyzed hydroamidation with IPr: (d) Li, H.; Widenhoefer, R. A. Org. Lett. 2009, 11, 2671. (8) Sipos, G.; Ou, A.; Skelton, B. W.; Falivene, L.; Cavallo, L.; Dorta, R. Chem. Eur. J. 2016, 22, 6939. (9) (a) Luan, X.; Mariz, R.; Robert, C.; Gatti, M.; Blumentritt, S.; Linden, A.; Dorta, R. Org. Lett. 2008, 10, 5569. (b) X. Luan, X.; L. Wu, L.; E. Drinkel, E.; R. Mariz, R.; M. Gatti, M.; R. Dorta, R. Org. Lett. 2010, 12, 1912. (c) Wu, L.; Falivene, L.; Drinkel, E.; Grant, S.; Linden, A.; Cavallo, L.; Dorta, R. Angew. Chem. Int. Ed. 2012, 51, 2870. (10) The ligand has recently been synthesized by Ogoshi: Kumar, R.; Tamai, E.; Ohnoshi, A.; Nishimura, A.; Hoshimoto, Y.; Ohashi, M.; Ogoshi, S. Synthesis 2016, 48, 2789. (11) Cationic iridium species are known to be sensitive to such changes, with [BArF24] providing superior catalysts, e.g. see: Woodmansee, D. H.; Pfaltz, A. In Iridium Catalysis; Anderson, P. G., Ed.; Springer-Verlag, Berlin/Heidelberg, 2011; Chapter 3, pp 31-76. (12) For reports on the synthesis of such iridium complexes: (a) Hintermair, U.; Gutel, T.; Slawin, A. M. Z.; Cole-Hamilton, D. J.; Santini, C. C.; Chauvin, Y. J. Organomet. Chem. 2008, 693, 2407. (b) Hintermair, U.; Englert, U.; Leitner, W. Organometallics 2011, 30, 3726. (c) Bohle, D. S.; Chua, Z. Organometallics 2015, 34, 1074. (13) The [NTf2] anion is by now well established in group 11 chemistry/catalysis: (a) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028. (b) Zheng, Z.; Wang, Z.; Wang, Y.; Zhang, L. Chem. Soc. Rev. 2016, 45, 4448. (c) Zi, W.; Toste, F. D. Chem. Soc. Rev. 2016, 45,4567.
(14) For an analysis of steric parameters, see: Sigman, M. S.; Miller, J. J. J. Org. Chem. 2009, 74, 7633. (15) For an overview, see: (a) Kirk, K. L. In Fluorinated Heterocyclic Compounds; Synthesis, Chemistry and Applications; Petrov, V. A., Ed.; Wiley & Sons, New Jersey, 2009; Chapter 2, pp 91-158. For recent synthetic efforts: (b) Si, C.; Fales, K. R.; Torrado, A.; Frimpong, K.; Kaoudi, T.; Vandeveer, H. G.; Njoroge, F. G. J. Org. Chem. 2016, 81, 4359. (c) Fedorov, O. V.; Struchkova, M. I.; Dilman, A. D. J. Org. Chem. 2017, 82, 3270. (16) 3[X] does not need to be part of the catalytic cycle and substitution of the product by the new incoming aminoolefin might be associative. (17) Zhou, J.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 12220, and references cited therein. (18) A pathway going through initial oxidative addition of the amine would very likely show significant differences in rates depending on subtle electronic changes of the amine, see: Sykes, A. C.; White, P.; Brookhart, M. Organometallics 2006, 25, 1664. (19) Lautens, M.; Fagnou, K.; Yang, D. J. Am. Chem. Soc. 2003, 125, 14884. (20) (a) Menshutkin, N. Z. Phys. Chem. Stoechiom. Verwandtschaftsl. 1890, 6, 41. (b) Nevstad, G. O.; Songstad, J. Acta Chem. Scand. 1984, 38, 469. (21) The most likely scenario would be that the cationic catalyst interacts with DCM, rendering its carbon atom more electrophilic and more susceptible to attack by the amine. (22) Cho, J. H.; Kim, B. M. Org. Lett. 2003, 5, 531. (23) The method developed here should be successful for neutral GI and GII catalysts, where contamination of the product is a major concern. (24) Dorta, R.; Egli, P.; Zurcher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119, 10857.
Table of Contents (TOC):
ACS Paragon Plus Environment
