3056
Z. Li et al.
LETTER
(5) Lopez, F. J.; Nitzan, D. Tetrahedron Lett. 1999, 40, 2071.
(6) Bullock, R. M. Angew. Chem. Int. Ed. 2007, 46, 7360.
(7) Berson, J. A.; Davis, R. F. J. Am. Chem. Soc. 1972, 94, 3659.
(8) Nakanishi, J.; Tatamidani, H.; Fukumoto, Y.; Chatani, N.
Synlett 2006, 869.
(9) Li, A. R.; Johnson, M. G.; Liu, J.; Chen, X.; Du, X.; Mihalic,
J. T.; Deignan, J.; Gustin, D. J.; Duquette, J.; Fu, Z.; Zhu, L.;
Marcus, A. P.; Bergeron, P.; McGee, L. R.; Danao, J.;
Lemon, B.; Carabeo, T.; Sullivan, T.; Ma, J.; Tang, L.; Tonn,
G.; Collins, T. L.; Medina, J. C. Bioorg. Med. Chem. Lett.
2008, 18, 688.
(10) Anada, M.; Tanaka, M.; Washio, T.; Yamawaki, M.; Abe,
T.; Hashimoto, S. Org. Lett. 2007, 9, 4559.
(11) Gu, Q.; Zheng, Y. H.; Li, Y. C. Synthesis 2006, 975.
(12) Bullock, R. M.; Song, J. S. J. Am. Chem. Soc. 1994, 116,
8602.
Reaction of substrate 1d under the ZnI2–TESH reaction
condition not only afforded the anticipated product 2d-1,
but also gave a dimer 2d-2 in 34% yield (Table 1, entry
4).23 We presumed that a Friedel–Crafts-like reaction
might happen between one completely reduced product
2d-1 and the other semireduced secondary alcohol in the
presence of a Lewis acid.24
For a,b-unsaturated enones, ZnI2–TESH system also
worked well in spite of incomplete conversion (entries
13–15). To our delight, the double bond, which is sensi-
tive to the usual organosilicon hydrides reduction condi-
tions,25 and many protection groups such as acetyl, TBS,
etc., exhibited good tolerance towards our new reduction
system.
(13) (a) Powell, D. A.; Batey, R. A. Org. Lett. 2002, 4, 2913.
(b) Malachowski, W. P.; Paul, T.; Phounsavath, S. J. Org.
Chem. 2007, 72, 6792.
(14) Deng, G.; Zhao, X. L.; Li, Z.; Jiang, B.; Li, Y. C.
unpublished results.
The reductive deoxygenation of ZnI2–TESH system was
also briefly investigated using other types of substrates
(Table 1, entries 16–18). We found that such system could
only reduce aliphatic ketone to its corresponding alcohol
in relatively low conversion ratio (entry 16). Because of
the special structure, artemisinin was reduced to dihy-
droartemisinin in 65% yield under our reaction conditions
(entry 17), which provided a new method to fulfill such
conversion for this important natural product.26 For sub-
strate 1r, instead of the desired deoxygenation product,
we obtained 2-cyclopropyl-4-trifluoromethyl-6-chloro-
quinoline in 89% yield (entry 18). So this is also a useful
supplement to an earlier reported Zn(II)-mediated alkyny-
lation–cyclization reaction of o-trifluoroacetyl anilines.27
(15) Ewing, G. J.; Robins, M. J. Org. Lett. 1999, 1, 635.
(16) Chochrek, P.; Wicha, J. J. Org. Chem. 2007, 72, 5276.
(17) Zheng, Y. H.; Li, Y. C. J. Org. Chem. 2003, 68, 1603.
(18) Blagg, B. S. Jr.; Boger, D. L. Tetrahedron 2002, 58, 6343.
(19) General Procedure for the Synthesis of Product 2: To a
stirred solution of substrate 1 (1 mmol) in 1,2-dichloroethane
(5 mL) at r.t. was added solid zinc iodide (638 mg, 2
mmol).Then, triethylsilane (1.9 mL, 10 mmol) was added
slowly to the above suspension via a syringe. The reaction
mixture was stirred at r.t. until 1 was completely disappeared
or there was no further conversion (TLC inspection). The
stirring was stopped, and then the reaction mixture was
filtered through Celite. The Celite was washed with CH2Cl2
(4 × 15 mL). The combined filtrate was washed with H2O
and sat. brine, and then dried over anhyd Na2SO4. After
concentration, the residue was chromatographed on silica
gel, eluting with 0–25% EtOAc in cyclohexane.
(20) Analytic Data for 4-Chloro-2-[2,2,2-trifluoro-1-(triethyl-
silyloxy)ethyl]aniline (2j): 1H NMR (300 MHz, CDCl3):
d = 0.62 (q, J = 7.9 Hz, 6 H), 0.92 (t, J = 7.9 Hz, 9 H), 3.93
(br s, 2 H), 4.94 (q, J = 7.2 Hz, 1 H), 6.60 (d, J = 8.5 Hz,
1 H), 7.09 (dd, J = 8.5, 2.5 Hz, 1 H), 7.15 (d, J = 2.5 Hz, 1
H). MS (EI): m/z (%) = 339 (39) [M+], 322 (4), 310 (43), 190
(32), 188 (100), 77 (36). HRMS (EI): m/z calcd for
C14H21NOSiClF3: 339.1033; found: 339.1041.
In conclusion, we have developed a mild and efficient re-
duction system, ZnI2–TESH, which could directly deoxy-
genate many types of carbonyl compounds such as aryl
aldehydes, ketones, and a,b-unsaturated enones to the
corresponding hydrocarbons. The good tolerance of many
sensitive groups and easy handling operations of ZnI2–
TESH significantly expand the application scope of ionic
hydrogenation reaction.
Supporting Information for this article is available online at
(21) Niyomura, O.; Iwasawa, T.; Sawada, N.; Tokunaga, M.;
Obora, Y.; Tsuj, Y. Organometallics 2005, 24, 3468.
(22) Toda, F.; Shigemasa, T. J. Chem. Soc., Perkin Trans. 1 1989,
209.
References and Notes
(23) Analytic Data for 5-[(4-Hydroxy-3-methoxyphenyl)-
methyl]-2-methoxy-4-methylphenol (2d-2): 1H NMR (300
MHz, CDCl3): d = 2.19 (s, 3 H), 3.80 (s, 2 H), 3.82 (s, 3 H),
3.86 (s, 3 H), 5.39–5.56 (m, 2 H), 6.61 (d, J = 7.7 Hz, 1 H),
6.63 (s, 1 H), 6.68 (d, J = 3.2 Hz, 2 H), 6.82 (d, J = 7.7 Hz,
1 H). 13C NMR (100 MHz, CDCl3): d = 19.2, 38.4, 55.8,
56.0, 111.1, 112.9, 114.1, 116.0, 121.3, 127.7, 132.0, 132.4,
143.3, 143.7, 144.6, 146.4. IR (KBr): 3384, 3022, 2931,
2835, 1608, 1513, 1460, 1431 cm–1. MS (EI):
(1) (a) Kursanov, D. N.; Parnes, Z. N.; Loim, N. M. Synthesis
1974, 633. (b) Larock, R. C. Comprehensive Organic
Transformations: A Guide to Functional Group
Preparations, 2nd ed.; Wiley: New York, 1999. (c)
Handbook of Reagents for Organic Synthesis: Oxidizing and
Reducing Agents; Burke, S. D.; Danheiser, R. L., Eds.;
Wiley & Sons: West Sussex, 1999.
(2) Poser, G. H.; Switzer, C. J. Am. Chem. Soc. 1986, 108, 1239.
(3) (a) Fry, J. L.; Orfanopoulos, M.; Aslington, M. G.; Dittman,
M. R. Jr.; Silverman, S. B. J. Org. Chem. 1978, 23, 374.
(b) Doyle, M. P.; West, C. T.; Donnelly, S. J.; Mcosker,
C. C. J. Organomet. Chem. 1976, 117, 129.
m/z (%) = 274 (100) [M+], 273 (6), 259 (33), 150 (38).
HRMS (EI): m/z calcd for C16H18O4: 274.1205; found:
274.1200.
(24) Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron Lett. 1998, 39,
6291.
(4) (a) Allin, S. M.; Northfield, C. J.; Page, M. I.; Slawin,
A. M. Z. Tetrahedron Lett. 1999, 40, 143. (b) Kano, S.;
Yokomatsu, T.; Iwasawa, H.; Shibuya, S. Tetrahedron Lett.
1987, 28, 6331.
Synlett 2008, No. 19, 3053–3057 © Thieme Stuttgart · New York