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A. Krasovskiy et al.
LETTER
Surprised with these results, we also examined reactions
of organozinc bromides with TMTD (1). Indeed, they be-
have similar to the organozinc chlorides and afford dithio-
carbamates 4b–c and 4e–f in comparable yields. No alkyl
bromides were detected. Also, ambident nucleophiles like
the Reformatsky reagent (2k), generated by direct inser-
tion of zinc dust into bromoacetic acid ethyl ester, reacts
cleanly with TMTD (1) exclusively as C-nucleophile, fur-
nishing the derivative of thioacetic acid (4g) in 82% yield
(entry 11).
References and Notes
(1) Solladié, G. In Comprehensive Organic Synthesis, Vol. 6;
Trost, B. M.; Fleming, I.; Winterfeld, E., Eds.; Pergamon
Press: Oxford, 1991, 133–170.
(2) (a) Banwell, M. G.; Flynn, B.; Hochlers, D. C. R. Chem.
Commun. 1997, 2259. (b) Banwell, M. G.; Flynn, B. L.;
Willis, A. C.; Hamel, E. Aust. J. Chem. 1999, 52, 767.
(c) Flynn, B. L.; Verdier-Pinard, P.; Hamel, E. Org. Lett.
2001, 3, 651. (d) Bates, C. G.; Gujadkur, R. K.;
Venkataraman, D. Org. Lett. 2002, 4, 2803. (e) Kwang, F.
Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517. (f) Savarin,
C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309.
(3) Krasovskiy, A.; Knochel, P. Synlett 2005, 2691.
(4) The price of tetramethylthiuram disulfide is 30 Euro per kg
(Aldrich).
In summary, we have shown that various classes of orga-
nozinc compounds react with TMTD (1) affording the
corresponding dithiocarbamates. The use of diorganozinc
derivatives gave the best results and very good yields
were obtained in all cases. This reaction can be further
extended to readily available functionalized alkyl zinc
reagents and proceeds with retention of configuration.
Extensions of this method are currently underway in our
laboratories.10
(5) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43,
3333.
(6) (a) Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-
Y.; Knochel, P. J. Org. Chem. 1996, 61, 8229. (b)Hupe, E.;
Calaza, M. I.; Knochel, P. J. Organomet. Chem. 2003, 680,
136. (c) Hupe, E.; Knochel, P. Angew. Chem. Int. Ed. 2001,
40, 3022. (d) Hupe, E.; Knochel, P. Chem. Eur. J. 2003, 9,
2789.
(7) Knochel, P.; Millot, N.; Rodrigues, A. L.; Tucker, C. E. Org.
React. 2001, 58, 417.
(8) This new redox reaction is actively investigated in our
laboratories.
(9) This lithium salt is readily prepared by treating TMTD (1) in
THF with MeLi (1 equiv, –20 °C, 10 min).
Acknowledgment
We thank the Fonds der Chemischen Industrie and Merck Research
Laboratories (MSD) for financial support. We thank Chemetall
GmbH (Frankfurt), BASF AG (Ludwigshafen) and Lanxess AG for
generous gifts of chemicals.
(10) Typical Procedure: Preparation of Myrtanyl
Dimethyldithiocarbamate (4d).
A 25-mL Schlenk flask containing a solution of TMTD (1.00
g, 4.16 mmol) in CH2Cl2 (5 mL) was cooled to 0 °C, and
bis(myrtanyl)zinc (510 mg, 1.5 mmol)6 was added slowly at
this temperature. The reaction mixture was stirred for 20 h at
r.t. (a white precipitate of zinc dimethyldithiocarbamate
formed), then was diluted with Et2O (30 mL) and filtered.
The precipitate was washed with Et2O, the filtrate
evaporated and the residue was purified by column
chromatography (pentane–CH2Cl2), yielding myrtanyl
dimethyldithiocarbamate as colorless crystals, mp 30–31 °C
(70% yield, 673 mg).
Synlett 2006, No. 5, 792–794 © Thieme Stuttgart · New York