Intramolecular aminocyanation of alkenes by N-CN bond cleavage

Article abstract of DOI:10.1002/anie.201310983

A metal-free, Lewis acid promoted intramolecular aminocyanation of alkenes was developed. B(C₆F₅)₃ activates N-sulfonyl cyanamides, thus leading to a formal cleavage of the N-CN bonds in conjunction with vicinal addition o

Full text of DOI:10.1002/anie.201310983

.
Angewandte
Communications
DOI: 10.1002/anie.201310983
Synthetic Methods
À
Intramolecular Aminocyanation of Alkenes by N CN Bond
Cleavage**
Zhongda Pan, Sarah M. Pound, Naveen R. Rondla, and Christopher J. Douglas*
Abstract: A metal-free, Lewis acid promoted intramolecular
aminocyanation of alkenes was developed. B(C6F5)3 activates
N-sulfonyl cyanamides, thus leading to a formal cleavage of the
À
N CN bonds in conjunction with vicinal addition of sulfona-
mide and nitrile groups across an alkene. This method enables
atom-economical access to indolines and tetrahydroquinolines
in excellent yields, and provides a complementary strategy for
regioselective alkene difunctionalizations with sulfonamide
and nitrile groups. Labeling experiments with 13C suggest
a fully intramolecular cyclization pattern due to the lack of
label scrambling in double crossover experiments. Catalysis
with Lewis acid is realized and the reaction can be conducted
under air.
Scheme 1. Carboamination of alkenes.
A
lkene addition reactions are a hallmark of organic
(Scheme 1) would allow straightforward access to b-amino-
nitriles. These compounds are versatile precursors to the
biologically and pharmacologically important b-amino
acids.[13] To our surprise, the well-developed strategies for
alkene aminofunctionalization[2–7] have only recently been
applied to the introduction of cyano groups onto the alkene
double bond. In 2013, Xiong, Li, Zhang, and co-workers
reported the first example of alkene aminocyanation. Their
work focused on aminocyanation of styrenes in an intermo-
lecular context and was thought to proceed by a copper-
promoted radical addition pathway using TMSCN as the
cyanide source and N-fluorobenzenesulfonimide as the nitro-
gen source.[14]
chemistry, yet significant problems remain unsolved.[1]
À
Recent successes include forming new C N bonds in con-
junction with vicinal C C, C O, C N, C H, or C X
[2,3]
[4]
[5]
[6]
[7]
À
À
À
À
À
bonds. These alkene aminofunctionalization reactions repre-
sent a unique strategy for the synthesis of valuable nitrogen-
containing heterocycles. Despite significant developments,
the established aminofunctionalization methods typically rely
upon an exogenous electrophile (e.g., aryl halides) or
nucleophile (e.g., halides, amines, carboxylates) to furnish
À
the subsequent C C or C–heteroatom bonds vicinal to the
nitrogen atom (Scheme 1).[8] To our knowledge, a direct
intramolecular addition approach to aminocyanation is unex-
plored.
1
2
À
Cyanamides (R R N CN) are versatile one-carbon, two-
nitrogen building blocks for heterocycle synthesis.[15] These
bench-stable compounds are easily prepared by reaction of
the corresponding secondary or tertiary amine with BrCN
(von Braun reaction).[16] While most transformations of
cyanamides occur at the cyano group, methods for cleaving
Recently, our group[9] and Nakaoꢀs group[10] independ-
ently reported two metal-catalyzed oxyfunctionalization
À
reactions of alkenes through the activation of O CO and
À
O CN bonds of esters and cyanates, respectively. Though this
early work was pioneering, the corresponding chemistry to
install a nitrogen atom is potentially more powerful. Due to
the versatile synthetic utility of the cyano group[11] and the
persistent demand for methods to prepare functionalized
nitriles,[12] we envisioned that the aminocyanation of alkenes
À
the N CN bond of cyanamides are rare, presumably due to
[17]
À
the double-bond character of N CN bonds. Owing to this
À
challenge, catalytic cleavage of N CN bonds has only recently
been reported.[18,19] Notably, Falck and Wang reported
a
rhodium-catalyzed cyano-group transfer from an
ortho cyanamide to the alkene of an a-methyl styrene. They
[*] Z. Pan, S. M. Pound, N. R. Rondla, Prof. Dr. C. J. Douglas
Department of Chemistry, University of Minnesota—Twin Cities
207 Pleasant St. SE, Minneapolis, MN 55455 (USA)
E-mail: cdouglas@umn.edu
À
proposed metal-mediated N CN bond cleavage as a key step
and the reaction required a relatively high catalyst loading
(20 mol% of Rh).[19] This N CN bond activation was
À
[**] We thank the National Institutes of Health for primary support of
this work (R01 GM095559). C.J.D. thanks Research Corporation for
Science Advancement for additional support through a Cottrell
Scholar Award. We thank Dr. Joe Dalluge and Sean Murray for
assistance with HRMS measurements. NMR spectra were recorded
on an instrument purchased with support from the National
Institutes of Health (S10OD011952).
conceptually in accord with our early mechanistic thinking
regarding alkene aminocyanation. Nevertheless, to the best of
our knowledge, intramolecular aminocyanation of alkenes—
by any mechanism—has never been described. Herein we
report a Lewis acid promoted intramolecular aminocyanation
of alkenes. We report the construction of 2,2-disubstituted
indolines[20] and 2,2-disubstituted tetrahydroquinolines in an
atom-economical fashion. The highlight of our approach is
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201310983.
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a novel mechanism for aminocyanation of alkenes by a non-
albeit in lower yields than B(C6F5)3 (entries 6–8). The reaction
À
degradative rupture at the N CN bond.
of AgOTf or Cu(OTf)2 with 1a failed to produce detectable
amounts of 2a, and instead gave complex mixtures (entries 9
and 10). Zn(OTf)2 or Sc(OTf)3 were also ineffective, return-
ing 1a without a detectable amount of 2a (entries 11 and 12).
Reaction of 1a with SnCl4 provided 2a in 49% (entry 13), but
also provided an insoluble black precipitate as a byproduct.
Interestingly, BPh3 was an ineffective promoter, even at
1508C (entry 14).
Recently, N-cyano-N-phenyl-p-toluene sulfonamide
(NCTS) has been employed as a bench-stable and less-toxic
cyanation reagent in metal-catalyzed cross-coupling[21] and
[22]
À
arene C H cyanations,
À
thus implying a metal-mediated
N CN cleavage process. Meanwhile, Lewis acid cocatalysts,
particularly BPh3, have proven effective at accelerating
metal-catalyzed carbocyanation[23] and oxycyanation[10] of
alkenes.
With the identification of suitable reaction conditions, the
scope of the Lewis acid promoted intramolecular amino-
cyanation was investigated. Substrates bearing alkyl (Table 2,
entries 1 and 2) or halo groups on the aromatic ring
(entries 3–5) provided the corresponding indolines in excel-
lent yields. It is worth noting that the presence of bromide
para to the cyanamide moiety (entry 5) was well-tolerated, as
this offers a convenient handle for further functionalization.
The electronic effects of para substituents on the aryl ring
appeared to be inconsequential as substrates containing
either electron-donating (R = Me, OMe; entries 1 and 7) or
electron-withdrawing (R = F, CF3; entries 3 and 6) groups
para to the cyanamide underwent the reaction in excellent
yields (ꢀ 92%). Substitution at the alkene, either alkyl or
phenyl, was tolerated and, in fact, necessary for the reaction.
The ethyl- and phenyl-substituted alkenes 1i and 1j, respec-
tively, (entries 8 and 9) afforded the corresponding indolines
in high yields. However, the allyl substrate 1n returned only
unconsumed starting material (entry 13). Substrates with
internal alkenes (including trisubstituted) provided complex
mixtures of products, and alkene substitution remains a lim-
itation at this time. The benzyloxymethyl-substituted alkene
1m also failed to provide product (entry 12), which was
tentatively attributed to the inductive effect of the benzyloxy
group.[25] An extended alkene tether found in the substrate 1k
afforded the tetrahydroquinoline 2k in 93% yield (entry 10).
Changing the protecting group at the nitrogen atom from
tosyl to nosyl (1l) provided the para-nosyl indoline 2l in
almost quantitative yield (99%, entry 11). The relatively mild
reaction conditions for cleaving nosyl groups should allow
convenient post-functionalization on the nitrogen atom.[26]
Additionally, methyl substitution ortho to the cyanamide
moiety (entry 14) was tolerated, giving 2o in 90% yield.
Based on the ability of B(C6F5)3 to promote intramolec-
ular aminocyanation, we needed to revise our mechanistic
thinking. Wang and co-workers recently reported that elec-
trophilic cyanations of indoles[27] is accomplished using NCTS
and a Lewis acid. This provides precedence for the nucleo-
We attempted to take advantage of the electron-with-
À
drawing tosyl group to weaken the N CN bond of NCTS-type
cyanamides while incorporating the activating effect of
a Lewis acid on the cyano group. Therefore, we initiated
our investigation of aminocyanation conditions by treating
the N-tosyl cyanamide 1a with a variety of transition-metal
and Lewis acid additives (see the Supporting Information for
details on discovery and optimization). We quickly identified
that the combination of rhodium(I) complexes and boron
Lewis acids were effective (Table 1, entries 1–4). As Lewis
acid strength increased from BPh3 to B(C6F5)3, the yield of 2a
improved from 49 to 72% with minimal amounts of the
Table 1: Development of aminocyanation conditions.
Entry
Metal[a]
Lewis acid[b]
T [8C]
Yield [%]
1
2
3
4
5
6
7
8
[{Rh(C2H4)2Cl}2]
[{Rh(C2H4)2Cl}2]
[{Rh(C2H4)2Cl}2]
[{Rh(C2H4)2Cl}2]
BPh3 (1.2 equiv)
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
BF3·OEt2
AlCl3
Me2AlCl
Ag(OSO2CF3)
Cu(OSO2CF3)2
Zn(OSO2CF3)2
Sc(OSO2CF3)3
SnCl4
110
110
90
80
90
90
90
90
90
90
90
90
90
49[c]
72[d]
89[d]
71[d]
90[d]
31[d]
52[d]
11[c]
–
–
–
–
–
–
–
–
–
–
[e]
9
–
–
–
[e]
10
11
12
13
14
[f]
[f]
–
49[c]
[f]
BPh3
150
–
[a] 5 mol% Rh complex used. [b] 1.0 equiv of Lewis acid was used unless
otherwise specified. [c] Determined by 1H NMR analysis using p-meth-
oxyacetophenone as the internal standard. [d] Yield after column
chromatography. [e] No 2a detected by NMR spectroscopy. Complex
mixture formed. [f] No 2a detected by NMR spectroscopy. Only 1a was
detected. Ts=p-toluenesulfonyl.
À
philic cleavage of N CN bonds and cyano-group transfer
under Lewis acid conditions. In aminocyanation, however,
both groups are transferred to the alkene. We hypothesized
that the NCN lone pair of electrons of 1a initially coordinated
to B(C6F5)3, affording the adduct I1 (Scheme 2).[28] This
coordination set the stage for an intramolecular nucleophilic
attack of the alkene, but the mode of attack was unclear.
reductive de-cyanation byproduct 3a observed (entry 2).[24]
Also, the temperature required for acceptable conversion of
1a could be decreased, with 908C proving optimal (entries 2–
4). Dramatically, a reaction employing B(C6F5)3 in the
absence of added rhodium still gave 2a in a 90% yield
(entry 5). This observation prompted us to examine other
Lewis acids to promote aminocyanation. The isoelectronic
Lewis acids BF3·OEt2, AlCl3, and Me2AlCl each provided 2a,
À
We considered a mechanism involving N CN cleavage by
aziridinium ion formation (path a, Scheme 2) and a nonfrag-
menting pathway involving nucleophilic attack of the alkene
at the central cyanamide carbon atom (path b, Scheme 2).
Aziridinium ion formation by B(C6F5)3-promoted loss of
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Table 2: Scope of alkene aminocyanation.[a]
Entry
Substrate
Product
Yield [%][b]
1
2
3
4
5
6
7
1b, R=Me
1c, R=tBu
1d, R=F
1e, R=Cl
1 f, R=Br
2b
2c
2d
2e
2 f
92
92[c]
>99
95
96
94
1g, R=CF3
1h, R=OMe
2g
2h
99
8
9
1i
1j
2i
2j
>99
>99
Scheme 2. Mechanistic experiments and considerations.
10d
1k
2k
2l
93
[13C]2a. The lack of crossover in the experiment indicated
that alkene aminocyanation proceeds in a fashion which is
inconsistent with the aziridinium ion hypothesis (Path A).[32]
The crossover experiments ruled out path a (Scheme 2).
We note that the success of cyanamides bearing more
nucleophilic alkenes (such as 1i and 1j) and the failure of
cyanamides bearing less nucleophilic alkenes (1m and 1n) is
consistent with rate-limiting alkene attack. The mechanism by
which the intermediate I3 is converted into product is not yet
11
12
1l
99
0
[e]
1m
–
À
clear. In principle, formation of the new C NTs bond could
À
occur either before or after rupture of the NTs CN bond.
Intriguingly, instead of giving the corresponding four-mem-
bered benzazetidine,[33] the reaction of the o-isopropenyl-
substituted cyanamide 1p led to the alkenyl nitrile 2pin
quantitative yield (Scheme 2, bottom).[34] These results show
that the type of cyano group transfer developed by Wang and
Falck does not require added rhodium. Future work will
explore the mechanistic consequence of this observation for
aminocyanation.
Our mechanistic hypothesis suggested that B(C6F5)3 might
act as a catalyst. To test this hypothesis, 1a was treated with
20 mol% B(C6F5)3 in toluene and heated at 908C for an
extended period (48 h). We were pleased to find that 2a was
formed in 91% yield. These results indicate that the
coordination of B(C6F5)3 to the product is not so strong as
to preclude turnover. Due to the relatively high cost of
commercial B(C6F5)3, cost-saving by catalysis may be ach-
ieved at the expense of reaction time. After a successful small-
scale reaction of 1c with 20 mol% B(C6F5)3 under nitrogen,
we repeated the reaction on larger scale, heating at 1008C for
48 hours under an atmosphere of air. We obtained 2c in 94%
yield (Scheme 3).
[e]
13
1n
–
0
14
1o
2o
90
[a] Reaction conditions: substrate (0.1 mmol), B(C6F5)3 (0.1 mmol),
PhMe (0.5 mL), 908C, 24 h. [b] Yields after column chromatography.
[c] Average of two runs. [d] Reaction time: 28 h. [e] Unconsumed starting
material. Ns=p-nitrobenzenesulfonyl.
cyanide was attractive due to the remarkable “anion abstract-
ing properties of this special boron compound”.[29,30] The
hypothesis involving nucleophilic attack of the alkene at the
central cyanamide carbon atom was attractive since this is the
typical site of nucleophile attack on cyanamides.[31] These
hypotheses were tested by a double-crossover experiment
(Scheme 2). A mixture of 1d and the 13C-labeled cyanamide
1a ([13C]1a) afforded only the non-crossover products 2d and
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W. H. Pearson), Wiley-Interscience, New York, 2002, pp. 539 –
623.
[4] Review: T. J. Donohoe, C. K. A. Callens, A. Flores, A. R. Lacy,
A. H. Rathi, Chem. Eur. J. 2011, 17, 58.
[5] Review: a) F. Cardona, A. Goti, Nat. Chem. 2009, 1, 269; b) K.
MuÇiz, C. Martꢁnez, J. Org. Chem. 2013, 78, 2168.
[6] Review: a) T. E. Mueller, K. C. Hultzsch, M. Yus, F. Foubelo, M.
Tada, Chem. Rev. 2008, 108, 3795; b) G. Zi, Dalton Trans. 2009,
9101.
[7] Review: a) G. Li, K. S. R. S. Saibau, C. Timmons, Eur. J. Org.
Chem. 2007, 2745; b) S. R. Chemler, M. T. Bovino, ACS Catal.
2013, 3, 1076.
[8] Intramolecular diamination of alkenes is an exception (Ref. [5]).
[9] G. T. Hoang, V. J. Reddy, H. H. K. Nguyen, C. J. Douglas,
Angew. Chem. 2011, 123, 1922; Angew. Chem. Int. Ed. 2011,
50, 1882.
[10] D. C. Koester, M. Kobayashi, D. B. Werz, Y. Nakao, J. Am.
Chem. Soc. 2012, 134, 6544.
[11] Three Carbon-Heteroatom Bonds: Nitriles, Isocyanides, and
Derivatives, Vol. 19 (Ed.: S. Murahashi), Georg Thieme, Stutt-
gart, 2004.
[12] A. Fatiadi in Preparation and Synthetic Application of Cyano
Compounds (Eds.: S. Patai, Z. Rappaport), Wiley, New York,
1983.
[13] a) G. Cardillo, C. Tomasini, Chem. Soc. Rev. 1996, 25, 117;
b) “Biosynthesis of b-Amino Acids”: P. Spiteller, F. von
Nussbaum in Highlights in Bioorganic Chemistry: Methods and
Application (Eds.: C. Schumck, H. Wennemers), Wiley-VCH,
Weinheim, 2004, pp. 63 – 89; c) E. Juaristi, V. A. Soloshonok,
Enantioselective Synthesis of b-Amino Acids, Wiley-VCH, New
York, 2005; d) B. Weiner, W. Szymanski, D. B. Janssen, A. J.
Minnaard, B. L. Feringa, Chem. Soc. Rev. 2010, 39, 1656.
[14] H. Zhang, W. Pu, T. Xiong, Y. Li, X. Zhou, K. Sun, Q. Liu, Q.
Zhang, Angew. Chem. 2013, 125, 2589; Angew. Chem. Int. Ed.
2013, 52, 2529.
Scheme 3. Catalysis with B(C6F5)3 and reaction under air.
In summary, we have developed a Lewis acid promoted
intramolecular aminocyanation of alkenes. The addition of
transition-metal catalysts or initiators is not required. We
believe we have identified a new mechanistic pathway for
aminative alkene difunctionalization by the addition of
bench-stable, readily available cyanamides. We demonstrated
the aminocyanation reaction in the preparation of two
important classes of nitrogen heterocycles, indolines and
tetrahydroquinolines, in excellent yields. Current efforts are
directed towards further elucidating the mechanism and
expanding the scope, as well as developing intermolecular
variants of aminocyanation. Further work will be directed
towards development of a catalytic asymmetric variant of the
reaction and further studies on the mechanism by probing the
stereochemistry of the addition process.
Received: December 18, 2013
Revised: February 6, 2014
Published online: April 9, 2014
Keywords: alkenes · boron · heterocycles · Lewis acids ·
.
reaction mechanisms
[1] Reviews: a) K. H. Jensen, M. S. Sigman, Org. Biomol. Chem.
2008, 6, 4083; b) R. I. McDonald, G. Liu, S. S. Stahl, Chem. Rev.
2011, 111, 2981.
[15] a) D. D. Nekrasov, Chem. Heterocycl. Compd. 2004, 40, 1107;
b) M.-H. Larraufie, G. Maestri, M. Malacria, C. Ollivier, L.
Fensterbank, E. Lacote, Synthesis 2012, 1279.
[2] Review: J. P. Wolfe, Top. Heterocycl. Chem. 2013, 32, 1. Selected
Examples a) L. S. Hegedus, G. F. Allen, D. J. Olsen, J. Am.
Chem. Soc. 1980, 102, 3583; b) Y. Tamaru, M. Hojo, H.
Higashimura, Z. Yoshida, J. Am. Chem. Soc. 1988, 110, 3994;
c) J. E. Ney, J. P. Wolfe, Angew. Chem. 2004, 116, 3689; Angew.
Chem. Int. Ed. 2004, 43, 3605; d) C. C. Scarborough, S. S. Stahl,
Org. Lett. 2006, 8, 3251; e) E. S. Sherman, P. H. Fuller, D. Kasi,
S. R. Chemler, J. Org. Chem. 2007, 72, 3896; f) S. Hayashi, H.
Yorimitsu, K. Oshima, Angew. Chem. 2009, 121, 7360; Angew.
Chem. Int. Ed. 2009, 48, 7224; g) C. F. Rosewall, P. A. Sibbald,
D. V. Liskin, F. E. Michael, J. Am. Chem. Soc. 2009, 131, 9488;
h) L. M. Rossiter, M. L. Slater, R. E. Giessert, S. A. Sakwa, R. J.
Herr, J. Org. Chem. 2009, 74, 9554; i) L. Bagnoli, S. Cacchi, G.
Fabrizi, A. Goggiamani, C. Scarponi, M. Tiecco, J. Org. Chem.
2010, 75, 2134; j) W. E. Brenzovich, D. Benitez, A. D. Lackner,
H. P. Shunatona, E. Tkatchouk, W. A. Goddard, F. D. Toste,
Angew. Chem. 2010, 122, 5651; Angew. Chem. Int. Ed. 2010, 49,
5519; k) S. Jaegli, W. Erb, P. Retailleau, J.-P. Vors, L. Neuville, J.
Zhu, Chem. Eur. J. 2010, 16, 5863; l) T. H. Jepsen, M. Larsen,
M. B. Nielsen, Tetrahedron 2010, 66, 6133; m) E. Borsini, G.
Broggini, A. Fasana, S. Galli, M. Khansaa, U. Piarulli, M.
Rigamonti, Adv. Synth. Catal. 2011, 353, 985; n) S. Nicolai, C.
Piemontesi, J. Waser, Angew. Chem. 2011, 123, 4776; Angew.
Chem. Int. Ed. 2011, 50, 4680; o) R. Jana, T. P. Pathak, K. H.
Jensen, M. S. Sigman, Org. Lett. 2012, 14, 4074.
[16] a) J. von Braun, Ber. Dtsch. Chem. Ges. Chem. 1907, 40, 3914;
Reviews: b) H. A. Hageman, Org. React. 1953, 7, 198; c) S.
Thavaneswaran, K. McCamley, P. J. Scammells, Nat. Prod.
Commun. 2006, 1, 885. CAUTION! Cyanogen bromide
(BrCN) is highly toxic and hydrolyzes readily to release hydro-
gen cyanide. Reactions using BrCN must be carried out in a well-
ventilated fume hood.
[17] a) I. D. Cunningham, M. E. Light, M. B. Hursthouse, Acta
Crystallogr. Sect. C 1999, 55, 1833; b) For an early example of
À
cleaving cyanamide N CN bonds under harsh reaction condi-
tions, see: E. B. Vliet, Org. Synth. 1925, 5, 43; c) cleaving
À
cyanamide N CN bond via aminocyanation of benzyne: B. Rao,
X. Zeng, Org. Lett. 2014, 16, 314.
[18] K. Fukumoto, T. Oya, M. Itazaki, H. Nakazawa, J. Am. Chem.
Soc. 2009, 131, 38.
[19] R. Wang, J. R. Falck, Chem. Commun. 2013, 49, 6516.
[20] For syntheses of 2,2-disubstituted indolines, see: a) R. C. Larock,
P. Pace, H. Yang, C. E. Russell, S. Cacchi, G. Fabrizi, Tetrahedron
1998, 54, 9961; b) F. Zhou, J. Guo, J. Liu, K. Ding, S. Yu, Q. Cai, J.
Am. Chem. Soc. 2012, 134, 14326; c) Q. Cai, F. Zhou, Synlett
2013, 408; d) F. Nowrouzi, R. A. Batey, Angew. Chem. 2013, 125,
926; Angew. Chem. Int. Ed. 2013, 52, 892.
[21] P. Anbarasan, H. Neumann, M. Beller, Angew. Chem. 2011, 123,
539; Angew. Chem. Int. Ed. 2011, 50, 519.
[22] a) M. Chaitanya, D. Yadagiri, P. Anbarasan, Org. Lett. 2013, 15,
4960; b) T.-J. Gong, B. Xiao, W.-M. Cheng, W. Su, J. Xu, Z.-J.
Liu, L. Liu, Y. Fu, J. Am. Chem. Soc. 2013, 135, 10630.
[23] Recent review: Y. Nakao, Bull. Chem. Soc. Jpn. 2012, 85, 731.
À
[3] Diazoalkane cycloadditions accomplish simultaneous C C and
À
C N bond forming across alkenes: “Diazoalkanes”: G. Maas in
Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry
Toward Heterocycles and Natural Products (Eds.: A. Padwa,
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[24] Nakao and co-workers observed reductive decyanation of the
cyanate substrates from the oxycyanation reactions (see
Ref. [19]).
[25] Subjecting 1m to the aminocyanation conditions with [{Rh-
(C2H4)2Cl}2] (5 mol%) and BPh3 (1.0 equiv) in toluene at 1108C
gave the product of decyanation (3m) and unconsumed starting
material.
[29] G. Erker, Dalton Trans. 2005, 1883.
[30] B(C6F5)3 is estimated to be in between BCl3 and BF3 in Lewis
acidity: S. Dçring, G. Erker, R. Froehlich, O. Meyer, K.
Bergander, Organometallics 1998, 17, 2183.
[31] For a recent example, see: R. L. Giles, J. D. Sullivan, A. M.
Steiner, R. E. Looper, Angew. Chem. 2009, 121, 3162; Angew.
Chem. Int. Ed. 2009, 48, 3116.
[26] T. Kan, T. Fukuyama, Chem. Commun. 2004, 353.
[27] Y. Yang, Y. Zhang, J.-B. Wang, Org. Lett. 2011, 13, 5608.
[28] Lewis acid/base pairs between isonitriles or nitriles and B-
(C6F5)3: a) H. Jacobsen, H. Berke, S. Dçring, G. Kehr, G. Erker,
R. Froehlich, O. Meyer, Organometallics 1999, 18, 1724;
b) Lewis acid/base pair adducts between B(C6F5)3 and cyana-
mides (and other nitrogen-containing compounds) F. Focante, P.
Mercandelli, A. Sironi, L. Resconi, Coord. Chem. Rev. 2006, 250,
170, and references therein.
[32] Similarly, an equimolar mixture of 1d and 1l was subjected to
the aminocyanation conditions, and only the corresponding
indoline products 2d and 2l were observed. This indicates the
À
N S bond also remains intact during aminocyanation.
[33] Synthesis of N-acyl benzazetidines: K. Kobayashi, K. Miyamoto,
O. Morikawa, H. Konishi, Bull. Chem. Soc. Jpn. 2005, 78, 886.
[34] 2o was identified by comparing its 1H and 13C NMR spectra and
HRMS data with the prior report (see Ref. [19]).
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