Nickel-Catalyzed Dearomative trans -1,2-Carboamination

Article abstract of DOI:10.1021/jacs.8b01726

We describe the development of an arenophile-mediated, nickel-catalyzed dearomative trans-1,2-carboamination protocol. A range of readily available aromatic compounds was converted to the corresponding dienes using Grignard reagents as nucleophiles. This strategy provided products with exclusive trans-selectivity and high enantioselectivity was observed in case of benzene and naphthalene. The utility of this methodology was showcased by controlled and stereoselective preparation of small, functionalized molecules.

Full text of DOI:10.1021/jacs.8b01726

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Nickel-Catalyzed Dearomative trans-1,2-Carboamination
Lucas W. Hernandez, Ulrich Klöckner, Jola Pospech, Lilian Hauss, and David Sarlah
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b01726 • Publication Date (Web): 15 Mar 2018
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Nickel-Catalyzed Dearomative trans-1,2-Carboamination
Lucas W. Hernandez, Ulrich Klöckner, Jola Pospech, Lilian Hauss, David Sarlah*
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Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States.
Supporting Information Placeholder
well as the noteworthy synthetic potential of the resultant
products, we wondered if the Ni-catalyzed process could be
translated into a general dearomative method. In addition to
examining the scope, the motivation for this work also included
ABSTRACT: We describe the development of an arenophile-
mediated, nickel-catalyzed dearomative trans-1,2-carboamination
protocol. A range of readily available aromatic compounds was
converted to the corresponding dienes using Grignard reagents as
nucleophiles. This strategy provided products with exclusive
trans-selectivity and high enantioselectivity was observed in case
of benzene and naphthalene. The utility of this methodology was
showcased by controlled and stereoselective preparation of small,
functionalized molecules.
the development of
a more practical and glovebox-free
enantioselective procedure. Herein we report these efforts,
resulting in general and efficient dearomative trans-1,2-
carboamination. The enantioselective protocol uses low catalyst
loadings of an air-stable Ni(II) precursor and permits the
application of a series of Grignard reagents. Moreover, a range of
aromatic precursors provides products with exclusive trans-
selectivity. Finally, the synthetic utility of the method is
demonstrated by selective elaboration of dearomatized products
into functionalized molecules.
The preparation of amines plays a crucial role in the synthesis
of natural products, polymers, and pharmaceuticals. Therefore,
ongoing efforts in modern organic synthesis includes the
development of novel catalytic methods that could streamline
their preparation, including functionalization of π-systems.1
Carboamination is one of the most powerful π-functionalization
strategies for the synthesis of amines, as it results in a formation
of C–C and C–N bonds with high atom- and step-economy.2 The
last decade has seen significant developments in this area, and
now several classes of these processes exists for alkenes,3
alkynes,4 and dienes.5 On the other hand, aromatic compounds
could also be considered as viable substrates,6 especially when
considering their availability and the synthetic versatility of the
corresponding unsaturated products.7 However, due to their
characteristic stability and reactivity, dearomative carboamination
of arenes is virtually nonexistent.8 To the best of our knowledge,
only transition-metal-catalyzed ring-opening of azabicyclic
alkenes can provide products resembling those of formal
dearomative 1,2-carboamination (Scheme 1A).9 Nevertheless,
these reactions require more elaborate, benzyne-derived starting
materials and cannot provide products resembling those obtained
from mononuclear arenes.
Scheme 1. Dearomative Carboaminations
To this end, we have recently disclosed a Pd-catalyzed
dearomative syn-1,4-carboamination10 as well as a total synthesis
of pancratistatins,11 which involved enantioselective, Ni-catalyzed
dearomative trans-1,2-carboamination of benzene as the first step
(Scheme 1B). The common design for both strategies involved
photochemical dearomative cycloaddition12 between an arene and
arenophile N-methyl-1,2,4-triazoline-3,5-dione (MTAD, 1),13
which also served as a nitrogen source. Since the reactivity of Pd
and Ni are intrinsically different, subsequent in situ transition-
metal-catalyzed ring-opening of MTAD-arene cycloadduct I with
carbon nucleophiles provided complementary syn-1,4- or trans-
1,2-carboaminated products. Thus, the observed selectivity is
likely the result of the outer-sphere attack of the enolate on Pd η3-
intermediate II14 and inner-sphere delivery of the Grignard
reagent in the case with cationic Ni η5-complex III.15
Considering the lack of dearomative difunctionalizations, as
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We commenced our investigations by repeating our initially
Grignard containing an olefin (2l) and 2-naphthalenemagnesium
bromide (2m) proved to be good substrates as well. Notably, this
difunctionalization strategy also enables the installation of alkene
moiety, as demonstrated using terminally (2n) and internally (2o)
substituted vinyl Grignard reagents.18 In addition to benzene, also
naphthalene underwent the desired asymmetric carboamination,
delivering product 2p in 60% yield and 94.5:5.5 er. It is important
to note that in all cases we consistently obtained products as a
single diastereoisomer. Finally, the scalability of this
enantioselective protocol was tested on a gram scale by examining
two reactions, using normal glass media bottles surrounded with
LEDs as photoreactors.19 Thus, products 2a and 2k were obtained
in 65% and 68% yield on multigram scale and without any
erosion in enantioselectivity.
reported conditions11 involving 10 mol% of [Ni(cod)2] and 20
mol% of (R,Rp)-iPr-Phosferrox, which was identified as the
optimal ligand for the desymmetrization of benzene (entry 1,
Table 1). Thus, using benzene and phenylmagnesium bromide, the
desired product 2a was formed in 70% yield and 95:5 er. Though
lowering catalyst loadings to 5/10 mol% did not result in
significant erosion in efficiency (entry 2), we decided to evaluate
a range of Ni(II) salts, which in combination with Grignard
reagent could serve as a precursor to Ni(0).16 Gratifyingly, a
variety of Ni(II) salts and complexes proved competent for this
process, including NiCl2 (42%, 90:10 er, entry 3), [Ni(dmg)2]
(51%, 90:10 er, entry 4), [NiCl2×glyme] (55%, 91:9 er, entry 5),
and [Ni(acac)2] (59%, 93:7 er, entry 6, see also Supporting
Information for full details). Interestingly, lowering catalyst
loading from 10/20 mol% resulted in beneficial effects on both
yield and enantioselectivity (entries 7–10). Thus, the most optimal
conditions found involved application of precatalyst consisting
from 1.5 mol% of [Ni(acac)2] and 2.0 mol% of (R,Rp)-iPr-
Phosferrox, delivering diene product 2a in 70% yield and 97:3 er
(entry 9).
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Table 2. Ni-Catalyzed Enantioselective Dearomative trans-
1,2-Carboaminationa
Table 1. Selected Optimization Studiesa
aStandard reaction conditions: MTAD (1, 0.5 mmol, 1.0 equiv),
benzene (5 mmol, 10 equiv), CH2Cl2 (0.20 M), visible light, −78
°C, 12 h; then PhMgBr (3M in THF, 1.25 mmol, 2.5 equiv), solu-
tion of catalyst [Ni precursor (x mol%), (R,Rp)-iPr-Phosferrox (y
aAll reactions were run on 0.5 mmol scale under the standard
conditions. For 2p, 1 mmol of naphthalene (2.0 equiv) was used.
Reported yields are of isolated products and er was determined by
HPLC analysis. bRun on 3.0g (26.5 mmol) scale. cRun on 6g (53.1
mmol) scale.
b
mol%), CH2Cl2], −45 °C→0 °C, 3 h. Isolated yield of pure 2a
after purification by flash chromatography. cDetermined using
HPLC analysis.
Next, we sought to explore if substituted arenes could be
suitable precursors for dearomative trans-1,2-carboamination
(Table 3). Unfortunately, in this case, the Ni(II) precatalyst
performed with notably lower efficiency compared to Ni(0). Thus,
we found that application of [Ni(cod)2] and 1,1'-
Having identified the optimal conditions for enantioselective
dearomative trans-1,2-carboamination, we then examined the
scope of Grignard reagents (Table 2). In addition to
phenylmagnesium bromide (2a), a range of para-substituted
analogues delivered products with high enantioselectivities (≥96:4
er, 2a–2g). Thus, halogens (2b–2d), an electron-rich phenol and
aniline derivative (2e and 2f), as well as benzyl alcohol derivative
(2g) proved compatible with this process. Noteworthy, no side
products resulting from potential Ni-catalyzed Kumada-type
bis(diphenylphosphino)ferrocene (dppf) as
a
ligand gave
consistently the best results. Though these substrates are not
amenable to enantioselective desymmetrization, we were excited
to find that a set of monosubstituted benzene derivatives as well
as polynuclear arenes showed the desired reactivity. For example,
substituted benzene derivatives containing an alkyl side chain
(3a), pivaloate-protected alcohols (3b and 3c), trifluoromethyl
(3d), and trimethylsilyl group (3e) were tolerated, all delivering
products with high selectivity. Only in two cases, did we observe
small amounts of constitutional isomers (9:1 for 3b and 11:1 for
3c). This high site-selectivity is consistent with reported examples
of nucleophile additions into stoichiometric cationic
cyclohexadienyl complexes, where addition preferentially occurs
at unsubstituted termini.20 Moreover, substituted polynuclear
arenes were also successful substrates (3f–3k), though lower
coupling16
were
observed
under
these
conditions.
Desymmetrization of benzene was also tested using more
sterically demanding, ortho-substituted aryl Grignard reagents
(2h–2j), which delivered products with comparable yields and
selectivities. Moreover, a 3,4-methylenedioxyphenyl group, a key
moiety for pancratistatins and other Amaryllidaceae alkaloids,17
was installed in 74% yield and 97:3 er (2k). This result is
comparable with our previous conditions (75%, 98:2 er, see
Scheme 1B, bottom) where higher loadings of [Ni(cod)2]/(R,Rp)-
iPr-Phosferrox (10/20 mol%) were needed. In addition, an aryl
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yields as well as constitutional isomers were observed with
monosubstituted naphthalenes (3i–3k). Thus, electron-rich
pivaloate-protected 2,3- and 1,4-dihydroxynaphthalene (3f and
naphthalene-based carboaminated product 2p was amenable to
further manipulations. It was converted to saturated amine 7 using
the same sequence as before. Alternatively, the arenophile moiety
could serve as an oxygen surrogate, as the urazole could be
readily converted to a ketone by simple oxidation with bleach,22
delivering arylketone 8. Finally, complete removal of the urazole
was accomplished through Birch reduction, furnishing 2-
phenyltetralin, a compound belonging to a class of potential drugs
for treatment of arrhythmias and rhinoviral infections.23
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3g), as well as
bis-acetal protected naphthalene-1,4-
dicarbaldehyde (3h) delivered the desired products with modest
yields. The observed ratio of constitutional isomers in
monosubstituted naphthalene series was highly dependent on the
position of the substituent. Thus, 1-substituted naphthalenes,
bearing more proximal substituents to the arene-MTAD
cycloadduct (3i and 3k) gave higher selectivity compared to more
distal, 2-substituted (3j). Finally, in addition to naphthalenes,
heteroarene such as quinoline derivative (3l), was also permitted
under these conditions.
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Table 3. Arene Scope of the Dearomative trans-1,2-
Carboaminationa
Figure 1. Derivatization of benzene- and naphthalene-derived
products 2a and 2o. Reagents and conditions: (a) (i) α-
bromoacetophenone, K2CO3, 94%; (ii) H2, Pt(s)/C (cat.), 91%;
then KOH, 73%; (b) (i) α-bromoacetophenone, K2CO3, 94%; (ii)
TPP, O2, visible-light, 65%; (iii) thiourea, then KOH, 73%; (c) (i)
α-bromoacetophenone, K2CO3, 94% (ii) MTAD, 68%; (iii) KOH,
then BzCl, then SmI2, 67%; (d) (i) α-bromoacetophenone, K2CO3,
91%; (ii) H2, Pt(s)/C (cat.), 92%; (iii) KOH, 82%; (e) (i) H2, Pd/C
(cat.), 95%; (ii) NaOCl, 53%; f) (i) H2, Pd/C (cat.), 95%; (ii) Li,
NH3, 69%.
In summary, we have reported a dearomative 1,2-trans-
carboamination, involving dearomative cycloaddition with an
arenophile and subsequent Ni-catalyzed substitution with a
Grignard reagent. A range of arenes and aryl or vinyl Grignard
reagents delivered products with exclusive 1,2-trans selectivity,
and high enantioselectivity when using benzene or naphthalene as
substrates. In addition to expanding the currently available
toolbox of dearomative transformations, this process also provides
a different disconnection approach when it comes to the
preparation of small, functionalized molecules. Considering no
other chemical or biological equivalent for dearomative 1,2-
carboamination exists, we anticipate the application of this
difunctionalization strategy in the preparation of natural products
and high-value added intermediates.
aReactions with mononuclear arenes were run on 0.5 mmol
scale under the standard conditions and with 10/20 mol% of
[Ni(cod)2]/dppf. For polynuclear arenes, 1 mmol (2.0 equiv)
starting arene was used. Reported yields are of isolated products
and the ratio of constitutional isomers (in parenthesis) was
determined by 1H NMR of the crude reaction mixtures.
ASSOCIATED CONTENT
Supporting Information
This material is available free of charge via the Internet at
http://pubs.acs.org.
Experimental procedures and spectral data for all new
compounds (PDF)
Crystallographic data (CIF)
This dearomative functionalization strategy sets the stage for
further elaborations as the corresponding products contain several
modifiable regions, including olefin and urazole motifs. For
example, benzene-derived product 2a could be converted to a
fully saturated aminocyclohexane 4 through diene hydrogenation
with Pt(S)/C and conversion of urazole to amine.21 Unsaturated
tetrasubstituted aminocyclitol derivative 5 was obtained through
singlet oxygen hetero-Diels–Alder reaction, subsequent thiourea-
mediated reduction of the corresponding endoperoxide, and
urazole cleavage. Similarly, diene 2a underwent [4+2]-
cycloaddition with MTAD, and double urazole fragmentation/N–
N-bond reduction to furnished unsaturated triamide 6. Also
AUTHOR INFORMATION
Corresponding Author
*sarlah@illinois.edu
Notes
The authors declare no competing financial interests.
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117, 13721. (b) Keane, J. M.; Harman, W. D. Organometallics 2005,
24, 1786. (c) See also Ref. 6d.
ACKNOWLEDGMENT
1
2
3
4
5
6
7
8
(9) For selected reviews involving ring-opening of unsaturated, strained
heterobicycles, see: (a) Lautens, M.; Fagnou, K.; Hiebert, S. Acc.
Chem. Res. 2003, 36, 48. (b) Rayabarapu, D. K.; Cheng, C.-H. Acc.
Chem. Res. 2007, 40, 971. (c) Woo, S.; Keay, B. A. Synthesis 1996,
6, 669. (d) Chiu, P.; Lautens, M. Top. Curr. Chem. 1997, 190. For
selected examples of formal dearomative 1,2-carboamination, see:
(e) Zhang, L.; Le, C. M.; Lautens, M. Angew. Chem., Int. Ed. 2014,
53, 5951. (f) Nishimura, T., Kawamoto, T., Sasaki, K., Tsurumaki,
E., and Hayashi, T. J. Am. Chem. Soc. 2007, 129, 1492; (g) Lautens,
M.; Dockendorff, C. Org. Lett. 2003, 5, 3695; (h) Ogura, T.; Yo-
shida, K.; Yanagisawa, A.; Imamoto, T. Org. Lett. 2009, 11, 2245;
(i) Chen, C.-L.; Martin, S. F. J. Org. Chem. 2006, 71, 4810; (j) Wu,
M.-S.; Rayabarapu, D. K.; Cheng, C.-H. J. Org. Chem. 2004, 69,
8407. For an early example of Ni-catalyzed ring opening of strained
oxabicyclic compounds using Grignard reagents, see: (k) Lautens,
M.; Ma, S. J. Org. Chem. 1996, 61, 7246.
(10)Okumura, M.; Shved, A. S.; Sarlah, D. J. Am. Chem. Soc. 2017, 139,
17787.
(11)Hernandez, L. W.; Pospech, J.; Klöckner, U.; Bingham, T. W.;
Sarlah, D. J. Am. Chem. Soc. 2017, 139, 15656.
(12)For reviews on dearomative cycloadditions, see: (a) Remy, R.;
Bochet, C. G. Chem. Rev. 2016, 116, 9816. (b) Wender, P A., Ter-
nansky, R., DeLong, M., Singh, S., Olivero, A., and Rice, K. Pure
Appl. Chem. 1990, 62, 1597. (c) McCullough, J. J. Chem. Rev. 1987,
87, 811.
(13)(a) Hamrock, S. J.; Sheridan, R. S. J. Am. Chem. Soc. 1989, 111,
9247. (b) Southgate, E. H.; Pospech, J.; Fu, J.; Holycross, D. R.; Sar-
lah, D. Nat. Chem. 2016, 8, 922.
(14)For reviews involving Pd-allyl intermediates, see: (a) Weaver, J. D.;
Recio, A., III; Grenning, A. J.; Tunge, J. A. Chem. Rev. 2011, 111,
1846. (b) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258. (c)
Trost, B. M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921. (d) Trost,
B. M.; Van Vranken, D. L. Chem. Rev. 1996, 96, 395.
(15)For reviews involving cationic cyclohexadienyl intermediates, see:
(a) Pike, R. D.; Sweigart, D. A. Coord. Chem. Rev. 1999, 187, 183.
(b) Pearson, A. J. Acc. Chem. Res. 1980, 13, 463. (c) Davies, S. G.;
Green, M. L. H.; Mingos, D. M. P. Tetrahedron 1978, 34, 3047.
(16)(a) Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972,
94, 4374. (b) Corriu, R. J. P.; Masse, J. P. Chem. Commun. 1972,
144.
(17)For a recent review describing these natural products, see: Ghavre,
M.; Froese, J.; Pour, M.; Hudlicky, T. Angew. Chem., Int. Ed. 2016,
55, 5642.
(18)Aliphatic, alkynyl, and heteroaromatic Grignard reagents, as well as
organomagnesium reagents prepared by magnesium-halogen ex-
change or magnesiations, did not react under the described reaction
conditions.
(19)For full descriptions and pictures of the photochemical setups, see
the Supplementary Information.
(20)For example, see: (a) Pearson, A. J.; Gelormini, A. M.; Pinkerton, A.
A. Organometallics 1992, 11, 936; (b) Bandara, B. M. R.; Birch, A.
J.; Kelly, L. F. J. Org. Chem. 1984, 49, 2496.
(21)Adam, W.; Pastor, A.; Wirth, T. Org. Lett. 2000, 2, 1295.
(22)(a) Wilson, R. M.; Hengge, A. C. J. Org. Chem. 1990, 55, 197. (b)
Wilson, R. M.; Hengge, A. C.; Ataei, A.; Ho, D. M. J. Am. Chem.
Soc. 1991, 113, 7240.
(23)For examples, see: (a) Koskelainen, T.; Otsomaa, L.; Karjalainen,
A.; Kotovuori, P.; Tenhunen, J.; Rasku, S.; Nore, P.; Tiainen, E.;
Tormakangas, O. WO Patent 2003/006452, 2003. (b) Hodson, H. F.;
Batchelor, J. F.; Selway, J. W. T.; Vinter, J. G.; Iyer, R. EP Patent
19800105462, 1984.
Financial support for this work was provided by the University of
Illinois, the National Science Foundation (CAREER Award No.
CHE-1654110), and the NIH/National Institute of General
Medical Sciences (R01 GM122891). D.S. is an Alfred P. Sloan
Fellow. L.H.W. acknowledges the NIH-NIGMS CBI Training
Grant as well as the NSF for a Graduate Fellowship (GRFP). J.P.
and U.K. thank the German Research Foundation (DFG) for
postdoctoral fellowships. We also thank Dr. D. Olson and Dr. L.
Zhu for NMR spectroscopic assistance, Dr. D. L. Gray and Dr. T.
Woods for X-ray crystallographic analysis assistance, and F. Sun
for mass spectrometric assistance.
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REFERENCES
(1) For recent reviews, see: (a) Pirnot, M. T.; Wang, Y.-M.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2016, 55, 48. (b) Huang, L.; Arndt, M.;
Gooßen, K.; Heydt, H.; Gooßen, L. J. Chem. Rev. 2015, 115, 2596.
(c) McDonald, R. I.; Liu, G.; Stahl, S. S. Chem. Rev. 2011, 111,
2981. (d) Hesp, K. D.; Stradiotto, M. ChemCatChem 2010, 2, 1192.
(e) Müller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M.
Chem. Rev. 2008, 108, 3795. (f) Hong, S.; Marks, T. J. Acc. Chem.
Res. 2004, 37, 673. (g) Müller, T. E.; Beller, M. Chem. Rev. 1998,
98, 675.
(2) For recent reviews, see: (a) Newhouse, T.; Baran, P. S.; Hoffmann,
R. W. Chem. Soc. Rev. 2009, 38, 3010. (b) Burns, N. Z.; Baran, P. S.
Angew. Chem., Int. Ed. 2008, 47, 205. (c) Wender, P. A.; Verma, V.
A.; Paxton, T. J.; Pillow, T. H. Acc. Chem. Res. 2008, 41, 40.
(3) For recent examples, see: (a) Gockel, S. N.; Buchanan, T. L.; Hull,
K. L. J. Am. Chem. Soc. 2018, 140, 58. (b) Qian, B.; Chen, S.;
Wang, T.; Zhang, X.; Bao, H. J. Am. Chem. Soc. 2017, 139, 13076.
(c) Liu, Z.; Wang, Y.; Wang, Z.; Zeng, T.; Liu, P.; Engle, K. M. J.
Am. Chem. Soc. 2017, 139, 11261. (d) White, D. R.; Hutt, J. T.;
Wolfe, J. P. J. Am. Chem. Soc. 2015, 137, 11246. (e) Piou, T.; Rovis,
T. Nature 2015, 527, 86. (f) Liwosz, T. W.; Chemler, S. R. J. Am.
Chem. Soc. 2012, 134, 2020.
(4) For recent examples, see: (a) Davis-Gilbert, Z. W.; Yao, L. J.;
Tonks, I. A. J. Am. Chem. Soc. 2016, 138, 14570. (b) Kajita, Y.;
Matsubara, S.; Kurahashi, T. J. Am. Chem. Soc. 2008, 130, 6058. (c)
Fürstner, A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127, 15024. (d)
Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004,
126, 10546. (e) Ruck, R. T.; Zuckerman, R. L.; Krska, S. W.;
Bergman, R. G. Angew. Chem., Int. Ed. 2004, 43, 5372.
(5) For recent examples, see: (a) Chen, S.-S.; Wu, M.-S.; Han, Z.-Y.
Angew. Chem. Int. Ed. 2017, 56, 6641. (b) Liu, Y.; Xie, Y.; Wang,
H.; Huang, H. J. Am. Chem. Soc. 2016, 138, 4314. (c) Houlden, C.
E.; Bailey, C. D.; Ford, J. G.; Gagné, M. R.; Lloyd-Jones, G. C.;
Booker-Milburn, K. I. J. Am. Chem. Soc. 2008, 130, 10066.
(6) For recent reviews on dearomatizations, see: (a) Roche, S. P.; Porco,
J. A. Angew. Chem., Int. Ed. 2011, 50, 4068. (b) Pouységu, L.;
Deffieux, D.; Quideau, S. Tetrahedron 2010, 66, 2235. (c) Lewis, S.
E. Chem. Commun. 2014, 50, 2821. (d) Pape, A. R.; Kaliappan, K.
P.; Kündig, E. P. Chem. Rev. 2000, 100, 2917. For recent reviews on
catalytic asymmetric dearomatizations, see: (e) Zhuo, C.-X.; Zhang,
W.; You, S.-L. Angew. Chem., Int. Ed. 2012, 51, 12662. (f) Zheng,
C.; You, S.-L. Chem, 2016, 1, 830.
(7) For selected recent examples involving dearomatizations, see: (a)
Good, S. N.; Sharpe, R. J.; Johnson, J. S. J. Am. Chem. Soc. 2017,
139, 12422. (b) Wilson, K. B.; Myers, J. T.; Nedzbala, H. S.;
Combee, L. A.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2017,
139, 11401. (c) Nakayama, H.; Harada, S.; Kono, M.; Nemoto, T. J.
Am. Chem. Soc. 2017, 139, 10188. (d) Zheng, J.; Wang, S.-B.;
Zheng, C.; You, S.-L. J. Am. Chem. Soc. 2015, 137, 4880. (e)
García-Fortanet, J.; Kessler, F.; Buchwald, S. L. J. Am. Chem. Soc.
2009, 131, 6676. (f) Zhuo, C.-X.; You, S.-L. Angew. Chem., Int. Ed.
2013, 52, 10056. (g) Phipps, R. J.; Toste, F. D. J. Am. Chem. Soc.
2013, 135, 1268. (h) Oguma, T.; Katsuki, T. J. Am. Chem. Soc.
2012, 134, 20017.
(8) Only certain dearomative reactions based on stoichiometric use of
Cr, Mo, W, and Os, can provide carbofunctionalized products, for
examples see: (a) Liebov, B. K., Harman, W. D. Chem. Rev. 2017,
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