series,8 the prototype N-carbamoyl diphenylamine 7a10 was
subjected to standard t-BuLi/TMEDA conditions to afford
product 9a in excellent yield (Table 1, entry 1).11 Application
Scheme 2. Alkyllithium-Mediated Transformation of
N-Protected Diarylamines into N-Aryl Anthranilates and N-Aryl
Anthranilamides
Table 1. Anionic Ortho N-Fries Rearrangement of N-CONEt2
Diarylamines 7a-g
regioselectivity. Herein we report on the scope and regiose-
lectivity of this new version of the anionic N-ortho-Fries
rearrangement,9 show its link to further DoM chemistry, and
demonstrate its application to the synthesis of acridone and
pyranoacridone alkaloids.
yield of yield of
entry
R
product conditionsa
8, %
9, %
1
2
3
4
5
6
7
8
9
10
11
12
13
14
H
H
8a/9a
8a/9a
8b/9b
8b/9b
8c/9c
8c/9c
8d/9d
8d/9d
8e/9e
8e/9e
8f/9f
A
B
A
B
A
B
A
B
A
B
A
B
A
B
81
90
26b
90b
35
90
14
90
92b
94b
87
97
19
51
Pursuant of improvement of the anionic N-Fries rearrange-
ment, and based on preliminary results from the N-BOC
3-OMe
3-OMe
4-OMe
4-OMe
3,5-OMe
3,5-OMe
3-Cl
3-Cl
4-Cl
4-Cl
2-Ph
59
6
54
4
75
7
(1) (a) Anionic ortho-Fries: Sibi, M. P.; Snieckus, V. J. Org. Chem.
1983, 48, 1935-1937. (b) Vinylogous anionic ortho-Fries: Kalinin, A. V.;
Miah, M. A. J.; Chattopadhyay, S.; Tsukazaki, M.; Wicki, M.; Nguen, T.;
Coelho, A. L.; Kerr, M.; Snieckus, V. Synlett 1997, 7, 839-841. (c) 1,5-
OfO CONEt2 translocation: Chauder, B. A.; Kalinin, A. V.; Taylor, N. J.;
Snieckus, V. Angew. Chem., Int. Ed. 1999, 38, 1435-1438. (d) Remote
anionic Fries: Wang, W.; Snieckus, V. J. Org. Chem. 1992, 57, 424-426.
(e) 1,2 Wittig versus 1,5-OfO CONEt2 translocation: Zhang, P.; Gawley,
R. E. J. Org. Chem. 1993, 12, 3222-3223. (f) Carbamoyl Baker-
Venkatarman reaction: Kalinin, A. V.; da Silva, A. J. M.; Lopes, C. C.;
Lopes, R. S. C.; Snieckus, V. Tetrahedron Lett. 1998, 39, 4995-4998. (g)
Anionic Friedel-Crafts equivalents: To acridones: MacNeil, S. L.; Gray,
M.; Briggs, L. E.; Li, J. J.; Snieckus, V. Synlett 1998, 4, 419-421. MacNeil,
S. L.; Gray, M.; Briggs, L. E., Snieckus, V. In preparation. (h) To
xanthones: Familoni, O. B.; Ionica, I.; Bower, J. F.; Snieckus, V. Synlett
1997, 9, 1081-1083. (i) To thiaxanthones: Beaulieu, F.; Snieckus, V. J.
Org. Chem. 1994, 59, 6508-6509. (j) To phosphorinones: Gray, M.;
Chapell, B. J.; Taylor, N. J.; Snieckus, V. Angew. Chem., Int. Ed. Engl.
1996, 35, 1558-1560. (k) Anionic OfR- and â-vinyl carbamoyl translo-
cation: Reed, M. A.; Chang, M. T.; Snieckus, V. Org. Lett. 2004, 6, 2297-
2300.
8f/9f
8g/9g
8g/9g
73
47
2-Ph
a Conditions: (A) 1. t-BuLi/TMEDA/-78 °C/Et2O/1 h; 2. -78 °C f
rt. (B) 1. LDA/0 °C/THF, 2. 0 °C f rt. b Migration to the 2-position occurs.
No 6-substituted product was observed.
of these favorable conditions to a series of N-carbamoyl
diarylamines 7b-g, prepared in 49-94% yields by a Pd-
catalyzed aryl amination protocol,12 furnished migration
products 8b-g and 9b-g in good to excellent yields and
regioselectivities (Table 1, entries 3, 5, 7, 9, 11, and 13). In
the absence of mechanistic studies for the anionic ortho
N-Fries process,11 including establishment of intramolecu-
larity,13 a rationale for the observed regioselectivities is
speculative. However, noteworthy are the following points:
(a) for 7b (entry 3), regioselective migration occurs into the
unsubstituted ring, which contrasts with that observed for
an N,N-diisopropyl 3′-methoxybiphenyl-2 carboxamide;14 (b)
for 7e (entry 9), migration takes place into the substituted
(2) (a) Snieckus, V. Chem. ReV. 1990, 90, 879-933. (b) Hartung, C.
G.; Snieckus, V. In Modern Arene Chemistry; Astruc, D., Ed.; Wiley-
VCH: Weinheim, Germany, 2002; pp 330-367.
(3) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem.,
Int. Ed. 2004, 43, 2206-2225.
(4) For a closely related example, see: Iwao, M.; Reed, N.; Snieckus,
V. J. Am. Chem. Soc. 1982, 104, 5531-5533.
(5) For general effects of m-EDG on Friedel-Crafts chemistry, see:
Taylor, R. In Electrophilic Aromatic Substitution; Wiley: New York, 1990;
p 236. For examples, see: Sargent, M. V. J. Chem. Soc., Perkin Trans. 1
1987, 2553. Fu, J.-m.; Zhao, B.-p.; Sharp. M. J.; Snieckus, V. Can. J. Chem.
1994, 72, 227-236. Sharp, M. J. M.Sc. Thesis, University of Waterloo,
1986.
(6) For other phenol- and aniline-based ortho anionic rearrangements,
at times effected not by DoM but by metal-halogen exchange, see, inter
alia: (a) ArOP(O)(OR)2: Cambie, R. C.; Plamer, B. D. Aust. J. Chem.
1982, 35, 827-837 and references therein. Melvin, L. S. Tetrahedron Lett.
1981, 22, 3375-3376. Dhawan, B.; Redmore, D. Phosphorus, Sulfur Silicon
Relat. Elem. 1991, 61, 183-187 and references therein. (b) ArOCOR:
Hellwinkel, D.; La¨mmerzahl, F.; Hofmann, G. Chem. Ber. 1983, 116, 3375-
3405 and references therein. (c) ArOSiR3: Billedeau, R. J.; Sibi, M. P.;
Snieckus, V. Tetrahedron Lett. 1983, 24, 4515-4518. (d) ArN(R)P(O)-
(OR)2: Jardine, A. M.; Vather, S. M. J. Org. Chem. 1988, 53, 3983-3985.
(e) ArN(R)COR: Horne, S.; Rodrigo, R. J. Chem. Soc., Chem. Commun.
1991, 1046-1048. Reference 7b. (f) ArN(R)SiR3: ref 7b. (g) ArN(SO2-
Ph)Ar′: Hellwinkel, D.; Supp, M. Chem. Ber. 1976, 109, 3749-3766.
Shafer, S. J.; Closson, W. D. J. Org. Chem. 1975, 40, 889-892. (h) For an
analogous migration of N-acylphenothiazines, see: Hallberg, A.; Svensson,
A.; Martin, A. R. Tetrahedron Lett. 1986, 27, 1959-1962.
(10) For C-7 DoM chemistry of N-CONEt2, 2-TMS-indole, see: Hartung,
C. G.; Fecher, A.; Chapell, B.; Snieckus, V. Org. Lett. 2003, 5, 1899-
1902.
(11) For detailed optimization studies, see: Wilson, B. M.Sc. Thesis,
Queen’s University, 2004.
(12) See: (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem.
Soc. 1996, 118, 7215-7216. For reviews, see: (b) Muci, A. R.; Buchwald,
S. L. Top. Curr. Chem. 2002, 219, 131-209. (c) Hartwig, J. F. In Modern
Arene Chemistry; Astruc, D., Ed.; Wiley-VCH: Weinheim, Germany, 2002;
pp 107-168.
(13) The lack of N-deprotected products and products possessing two
amide substituents, one at nitrogen and one at the ortho- or ortho′-position,
which would arise by an intermolecular N f C carbamoyl migration,
suggests but does not prove an intramolecular mechanism for the reaction.
(14) Under LDA conditions, this compound gives 1-methoxyfluoren-9-
one, the result of remote metalation-cyclization, see: Fu, J.-m.; Zhao, B.-
p.; Sharp, M. J.; Snieckus, V. J. Org. Chem. 1991, 56, 1683-1685. For an
indication of the generality of this reaction, see ref 3.
(7) For an interesting migration in a thiophene 2-sulfonamide, see:
Slocum, D. W.; Gierer, P. L. J. Org. Chem. 1973, 38, 4189-4192.
(8) Detailed studies will be the subject of a full paper. See also: MacNeil,
S. L. M.Sc. Thesis, University of Waterloo, 1997.
(9) For reports on rearrangements of different N-groups, see refs 7d-h.
1134
Org. Lett., Vol. 8, No. 6, 2006