Angewandte
Chemie
4.06 ppm (s, 3H); 13C NMR (75.5 MHz): d = 157.3, 137.3, 131.7, 129.7,
(Table 1, entry 8) also proved unexceptional. N-Ans-pyrrole
and indole[15] are smoothly deprotected. However, N-Ans-
allyl amines are not compatible with the hydrodesulfonylation
conditions and give products of deallylation.[16]
120.2, 113.2, 56.6 ppm; LRMS (EI): m/z (%): 205 [M+] (1), 163 (10),
83 (58), 81 (39), 67 (16), 55 (100).
N-Benzylphenylamine (3i): A solution of iPrMgCl (6.34mL,
2.13m in Et2O, 13.5 mmol) was added to a solution of 2s (1.06 g,
3.0 mmol) and [Ni(acac)2] (39.0 mg, 0.15 mmol) in Et2O (80 mL), and
the reaction mixture stirred at room temperature for 2 h. The reaction
was quenched with saturated NH4Cl solution, and the aqueous layer
was extracted twice with EtOAc. The organic layer was washed three
times with saturated NH4Cl solution, once with H2O, and once with
brine. The solution was dried (Na2SO4), and the solvent was removed
The poor reaction of N-Ts amines 4 has thus far precluded
its
deprotection
under
Ni0-catalyzed
conditions
(Scheme 2).[17] However, the widespread use of the Ts
protecting group makes the development of a Ni0-catayzed
deprotection protocol a priority. To this end, preliminary
experiments with oxazolidine 5 indicate that Ni–phosphane
catalysts, extended reaction times (12–18 h), and the use of a
large excess of the Grignard reagent result in increased yields
of the product of N-Ts cleavage.[18]
in vacuo to give 3i (395 mg, 95%) as
a colorless solid after
chromatography (20:1 hexane/EtOAc). M.p. 35.5–37.88C (Lit.[21]);
1H NMR (300 MHz): d = 7.38–7.13 (m, 7H), 6.78–6.50 (m, 3H),
4.87 ppm (br s, 1H), 4.26 (s, 2H); 13C NMR (50.3 MHz): d = 148.1,
139.4, 129.2, 128.5, 127.4, 127.1, 117.5, 112.8, 48.2.
Received: August 12, 2003 [Z52634]
Keywords: amines · magnesium · nickel · protecting groups ·
.
sulfonamides
[1] a) Protective Groups in Organic Synthesis, 3rd ed. (Eds.: T. W.
Green, P. G. Wuts), Wiley, New York, 1999, pp. 600 – 613; b) P. J.
Kocienski, ProtectingGroups , 2nd ed., Theime, Stuttgart, 2000.
[2] B. J. Paul, E. Hobbs, P. Buccino, Hudlicky, T. Tetrahedron Lett.
2001, 42, 6433.
[3] C. J. Opalka, T. E. D'Ambra, J. J. Faccone, G. Bodson, E.
Cossement, Synthesis 1995, 7, 766.
[4] For recent developments, see 2-nitrophenylsulfonyl (cleavage
PhSH/K2CO3/DMF): a) T. Fukuyama, C.-k. Jow, M. Cheung,
Tetrahedron Lett. 1995, 36, 6373; b) W. Kurosawa, T. Kan, T.
Fukuyama, Org. Synth. 2002, 79, 186; c) T. Messeri, D. D.
Sternbach, N. C. O. Tomkinson, Tetrahedron Lett. 1998, 39, 1669;
p-toluenesulfonyl cleavage (SmI2): d) E. Vedejs, S. Lin, J. Org.
Chem. 1994, 59, 1602; e) D. C. Hill, L. A. Flugge, P. A. Petillo, J.
Org. Chem. 1997, 62, 4864; Ti0: f) S. K. Nayak, Synthesis 2000, 11,
1575.
Scheme 2. Ni0-catalyzed hydrodesulfonylation of N-Ts amines.
dppp=propane-l,3-diylbis(diphenylphosphane)
To conclude, the N-Ans group constitutes a new amine-
protecting group that overcomes the necessity for harsh
cleavage conditions normally demanded by the N-Ts and
related sulfonamides.[1] Furthermore, its value for the syn-
thesis of unsymmetrical secondary amines and primary
amines has been demonstrated. Although the scope and
limitations of the new methodology, and hence its potential
complementarity to the Fukuyama[4a,b,10] and Gabriel[19]
syntheses of primary amines, remains to be established, it
allows a significant departure from the classical N-Ts
deprotection modes.[20] The combined advantages of conven-
ient derivatization with mild and rapid deprotection bodes
well for its broader application in organic synthesis.
[5] Sharpless asymmetric aminohydroxylation: a) V. V. Fokin, K. B.
Sharpless, Angew. Chem. 2001, 113, 3463; Angew. Chem. Int. Ed.
2001, 40, 3455; b) P. O'Brien, Angew. Chem. 1999, 111, 339;
Angew. Chem. Int. Ed. 1999, 38, 326; for a short review on the
scope and limitations, see: c) D. Nilov, O. Reiser, Adv. Synth.
Catal. 2002, 344, 1169, for recent work, see: d) T. J. Donohoe,
P. D. Johnson, A. Cowley, M. Keenan, J. Am. Chem. Soc. 2002,
124, 12934; e) V. Nesterenko, J. T. Byers, P. J. Hergenrother,
Org. Lett. 2003, 5, 281; asymmetric addition to imines: f) R. Hori,
T. Aoya ma, T. Shioiri, Tetrahedron Lett. 2000, 41, 9455;
g) G. K. S. Prakash, M. Mandal, Olah, G. A. M. Ueda, A.
Saito, N. Miyaura, Synlett 2000, 11, 1637; h) W. Lu, T. H. Chan, J.
Org. Chem. 2001, 66, 3467; aziridination: i) L. Simkhovich, Z.
Gross, Tetrahedron Lett. 2001, 42, 8089; j) P. Dauban, R. H.
Dodd, Tetrahedron Lett. 2001, 42, 1037; k) B. M. Chana, R. Vyas,
A. V. Bedekar, J. Org. Chem. 2001, 66, 30; l) S. Handy, M. Czopp,
Org. Lett. 2001, 3, 1423; m) M. T. Baros, C. D. Maycock, M. R.
Ventura, Tetrahedron Lett. 2002, 43, 4329; n) J. J. Caldwell, D.
Craig, S. P. East, Synlett 2001, 1602; o) V. K. Aggarwal, E.
Alonso, M. Ferrara, S. E. Spey, J. Org. Chem. 2002, 67, 2335;
p) D. Caine, P. O'Brien, C. M. Rosser, Org. Lett. 2002, 4, 1923;
q) K. M. Gillespie, C. J. Sanders, P. O'Shaughnessy, I. West-
moreland, C. P. Thickitt, P. Scott, J. Org. Chem. 2002, 67, 3450;
r) L. Simkhovich, Z. Gross, Tetrahedron Lett. 2001, 42, 8089; a-
amino acid synthesis: (cleavage: Na/NH3) s) E. Fischer, Ber.
Dtsch. Chem. Ges. 1915, 48, 93; t) V. du Vigneaud, O. K.
Behrens, J. Biol. Chem. 1937, 212, 27; (cleavage HBr/HOAc)
u) B. E. Haskell, S. B. Bowlus, J. Org. chem. 1976, 41, 159; b-
Experimental Section
2-Methoxybenzenesulfonyl chloride (1):[20] nBuLi (35.4mL, 2.85 m,
101 mmol) was added to a solution of TMEDA (15.2 mL, 101 mmol)
in Et2O (200 mL) at 08C, and the reaction mixture was stirred for
5 min. Anisole (10 mL, 92 mmol) was added and the mixture was
stirred for 1 h, cooled to À 788C, treated with SO2 (g) passed through
a syringe for 30 min, and allowed to warm to room temperature over
1 h. SO2Cl2 (8.8 mL 110 mmol) was added, and the mixture was
stirred at room temperature for 6 h. The mixture was partitioned
between Et2O and H2O, the organic layer was separated, washed with
brine, and dried (Na2SO4), and the solvent was removed in vacuo to
give AnsCl (10.1 g, 81%). M.p. 53–548C (hexanes) [Lit.[21] m.p. 568C];
1H NMR (300 MHz): d = 7.95 (dd, 1H, J = 8.0, 1.7 Hz), 7.70(ddd, 1H,
J = 8.5, 7.5, 1.7 Hz), 7.13 (t, 1H, J = 8.3 Hz), 7.09 (d, 1H, J = 7.5 Hz),
Angew. Chem. Int. Ed. 2004, 43, 892 –892
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893