Improved Procedure for the Synthesis of
gem-Diiodoalkanes by the Alkylation of
Diiodomethane. Scope and Limitations
James A. Bull and Andre´ B. Charette*
De´partement de Chimie, UniVersite´ de Montre´al,
PO Box 6128, Station Downtown, Montre´al, Que´bec,
Canada H3C 3J7
FIGURE 1. Synthetic routes to gem-diiodoalkanes.
ReceiVed July 3, 2008
recently reported a diimide reduction of 1,1-diiodoalkenes
to form a range of gem-diiodides.8
Despite these available methods, the use of the gem-diiodides
in the synthesis of complex molecules remains scarce,10-12 and
there are few examples of the preparation of highly function-
alized gem-diiodide reagents. This is presumably due to the often
low yields and low functional group tolerance in the preparation
of the gem-diiodides or of the required precursors.
As part of our ongoing investigations into cyclopropanation
methodologies, we required the synthesis of functionalized
diiodide 2a, containing a THP-protected allylic alcohol (eq 1).
We chose to examine the alkylation of diiodomethane with
alkyliodides, believing this would be compatible with the
functionality present and allow the generation of sufficient
quantities of material.13,14 This approach was originally reported
by Seyferth and Lambert, forming LiCHI2 from CHI3 with
n-BuLi, at -95 °C due to the low thermal stability of the
anion.13 In 1990 Verpeaux et al. used NaHMDS to deprotonate
diiodomethane, also at very low temperatures.14 In both cases
Functionalized gem-diiodoalkanes are obtained in good to
excellent yields by employing a convenient modified pro-
cedure for the alkylation of NaCHI2 with alkyl iodides.
Complete conversion to the diiodide is reliably obtained,
avoiding a problematic separation of any remaining iodide
starting material. Functional group tolerance toward olefins,
acetals, ethers and silyl ethers, carbamates, and hindered
esters is demonstrated. The use of an excess of LiCHI2 allows
complete conversion of allyl and benzyl bromides with
minimal elimination from the diiodide product.
(7) (a) Use of AlCl3/EtI: Letsinger, R. L.; Kammeyer, C. W. J. Am. Chem.
Soc. 1951, 73, 4476–4476. (b) Use of FeCl3/NaI: Miller, J. A.; Nunn, M. J.
Tetrahedron Lett. 1974, 15, 2691–2694. (c) Hsu, M.-C.; Jwo, J.-J. J. Chin. Chem.
Soc. 1989, 36, 403–412. (d) Use of AlI3: Anson, C. E.; Sheppard, N.; Powell,
D. B.; Norton, J. R.; Fisher, W.; Keiter, R. L.; Johnson, B. F. G.; Lewis, J.;
Bhattacharrya, A. K.; Knox, S. A. R.; Turner, M. L. J. Am. Chem. Soc. 1994,
116, 3058–3062.
(8) Cloarec, J.-M.; Charette, A. B. Org. Lett. 2004, 6, 4731–4734.
(9) Othermethodsforthesynthesisofgem-diiodides.(a)Fromacetals:Gonza´lez,
C. C.; Kennedy, A. R.; Leo´n, E. I.; Riesco-Fagundo, C.; Sua´rez, E. Angew. Chem.,
Int. Ed 2001, 40, 2326–2328. (b) From an aldehyde using TMSI: Jung, M. E.;
Mossman, A. B.; Lyster, M. A. J. Org. Chem. 1978, 43, 3698–3701.
(10) For recent examples of the use of functionalized diiodoalkanes in
cyclopropanation reactions, see: (a) Charette, A. B.; Lemay, J. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1090–1092. (b) Liu, P.; Jacobsen, E. N. J. Am. Chem.
Soc. 2001, 123, 10772–10773.
gem-Diiodoalkanes are valuable precursors to organome-
tallic reagents employed in carbon-carbon bond-forming
reactions. Their most notable uses include the Simmons-Smith
cyclopropanation1 and the Takai-Utimoto olefination reac-
tions.2 Several methods are available for preparation of
alkyl-diiodides,3-9 including the reaction of iodine with
hydrazones,3 metallated alkynes,4 or diazo compounds (Figure
1).5 Triflylacetals6 and dichloroalkanes7 can be converted to
alkyldiiodides by treatment with metal iodides, and our group
(1) (a) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc. 1959, 81, 4256–
4264. (b) Charette, A. B.; Beauchemin, A. Org. React. 2001, 58, 1–415. (c)
Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. ReV. 2003, 103,
977–1050.
(2) (a) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108, 7408–
7410. (b) Okazoe, T.; Takai, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109,
951–953. (c) Takai, K.; Kunisada, Y.; Tachibana, Y.; Yamaji, N.; Nakatani, E.
Bull. Chem. Soc. Jpn. 2004, 77, 1581–1586.
(3) (a) Furrow, M. E.; Myers, A. G. J. Am. Chem. Soc. 2004, 126, 5436–
5445. (b) Pross, A.; Sternhell, S. Aust. J. Chem. 1970, 23, 989–1003. (c) Barton,
H. H. R.; O’Brien, R. E.; Sternhell, S. J. Chem. Soc. 1962, 470–476.
(4) (a) Aufauvre, L.; Knochel, P.; Marek, I. Chem. Commun. 1999, 2207–
2208. (b) Varghese, J. P.; Zouev, I.; Aufauvre, L.; Knochel, P.; Marek, I. Eur.
J. Org. Chem. 2002, 4151–4158.
(5) (a) Neuman, R. C., Jr.; Rahm, M. L. J. Org. Chem. 1966, 31, 1857–
1859. (b) Moss, R. A. J. Org. Chem. 1965, 30, 3261–3265.
(6) Garcia Mart´ınez, A.; Herrera Ferna´ndez, A.; Mart´ınez, Alvarez, R.; Garcia
Fraile, A.; Bueno Calderon, J.; Osio Barcina, J.; Hanack, M.; Subramanian, L. R.
Synthesis 1986, 1076–1078.
(11) For recent examples of of the use of functionalized diiodoalkanes in
olefination reactions, see: (a) Stragies, R.; Blechert, S. J. Am. Chem. Soc. 2000,
122, 9584–9591. (b) Su, Q.; Dakin, L. A.; Panek, J. S. J. Org. Chem. 2007, 72,
2–24. (c) Johnson, D. V.; Felfer, U.; Griengl, H. Tetrahedron 2000, 56, 781–
790. (d) Dixon, D. J.; Ley, S. V.; Lohmann, S.; Sheppard, T. D. Synlett 2005,
481–484.
(12) (a) Enantioselective synthesis of allenes via RCHI(ZnBu): ref 4b. (b)
Diasteroselective addition to aldehydes using RCHI(SmI2): Matsubara, S.;
Yoshioka, M.; Utimoto, K. Angew. Chem., Int. Ed. Engl. 1997, 36, 617–618.
(c) Diastereo-, enantioselective epoxidation via RCHI(MgCl): Schulze, V.;
Hoffmann, R. W. Chem. Eur. J. 1999, 5, 337–344. (d) Cross coupling via
RCHI(ZnI)2: Yoshino, H.; Toda, N.; Kobata, M.; Ukai, K.; Oshima, K.; Utimoto,
K.; Matsubara, S. Chem. Eur. J. 2006, 12, 721–726. (e) Chain extension via
EtZnCHIR: Lin, W.; McGinness, R. J.; Wilson, E. C.; Zercher, C. K. Synthesis
2007, 2404–2408.
(13) Seyferth, D.; Lambert, R. L., Jr. J. Organomet. Chem. 1973, 54, 123–
130.
(14) Charreau, P.; Julia, M.; Verpeaux, J. N. Bull. Soc. Chim. Fr. 1990, 127,
275–282.
10.1021/jo8014616 CCC: $40.75
Published on Web 09/13/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8097–8100 8097