overaddition.4 The challenge was that, whereas there are
>360 reports on the substitution of I for TMS, there is
none, according to an exhaustive SciFinder search, on the
iododesilylation of TIPS alkenes,5 of tert-butyldiphenylsi-
lyl alkenes (CꢀTBDPS cleavage), or even of the less
sterically crowded TBS alkenes.6 In this connection, it is
worth noting a very recent report by Zakarian et al.7 on the
use of polar, non-nucleophilic (CF3)2CHOH (1,1,1,3,3,3-
hexafluoro-2-propanol, “hexafluoroisopropanol”, HFIP)
as the solvent of choice to iodinate TMS alkenes and
PhMe2Si alkenes with N-iodosuccinimide (NIS).8 Would
these iododesilylation conditions, the best reported to date,7
allow the conversion of IVaꢀc into IIaꢀc without affecting
other CꢀSiR3 bonds as well as standard functional groups?
We first examined the reactions of 4-phenyl-1-butene
and 4-phenyl-1-butyne derivatives shown in Scheme 2 with
NIS in HFIP/CDCl3, by NMR spectroscopy. For exam-
ple, when an equimolar mixture of 1, 2, and 3 in 1:1 HFIP/
CDCl3 was treated with NIS at 0 °C and its NMR
spectrum was registered at 20 °C, only the olefinic signals
of 1 decreased. A mixture of 1 and 4a, treated with a
substoichiometric amount of NIS, gave rise to the dis-
appearance of 4a to form vinyl iodide 5a, with retention of
the double-bond configuration; only when more NIS was
added, did 1 disappear. In another competition experiment
between 4a and 4b, no difference in the reaction rate of
4a (to give 5a) and 4b (to give 5b) was detected, even
at ꢀ20 °C. Thus, TIPS-substituted alkenes (Z and E) could
be transformed into vinyl iodides under these conditions,
with retention of the configuration, in the presence of
alkenes, alkynes, and silylated alkynes.
several byproducts began to appear while some starting
material still remained (long reaction times being
contraindicated). We hypothesized that radical reactions
affording HI by hydrogen abstraction and I2 (from the
dimerization of iodine atoms or from the reaction of HI
with remaining NIS) may promote the cleavage of some
OꢀPG bonds and the opening of the epoxide rings; be-
sides, I2 and HI may add to reactive double bonds. After a
series of experiments with different amounts of silver salts
and/or bases to trap these impurities, we found that in the
presence of 30 mol % of Ag2CO3 no pink color appeared
during the reactions in which we used 1.2 equiv of NIS. A
mixture of AgOAc (0.3ꢀ0.4 equiv) and 2,6-lutidine
(0.3ꢀ0.4 equiv)11 was similarly efficient. With either of
these two procedures, no byproducts were formed; the
conversions were 100%, with isolated yields around 90%
(see Table 1).
Table 1 shows that enyne 4c (entry 3 of Table 1), dienes
4d and 4e (entries 4 and 5), and compounds with OꢀSi
bonds (entries 4, 5, 7, and 8) only undergo the desired
C(sp2)ꢀTIPS bond cleavage. CꢀTBDPS and CꢀTBS
bonds can also be cleaved (entries 9ꢀ12).
Other iodinating reagents such as N-iodosaccharin
(NISac),12 1,3-diodo-5,5-dimethylhydantoin (DIH),13
and bis(pyridine)iodonium tetrafluoroborate (Ipy2BF4),
a reagent developed by Barluenga’s group,14 were exam-
ined (Table 1, last three columns). These reagents were
similarly efficient. As reactions with Ipy2BF4 were slower
but did not give rise to secondary reactions, they were
allowed to warm to rt;15 the advantage of this reagent is
that the addition of Ag2CO3 or AgOAc/2,6-lutidine is
unnecessary.
Scheme 2. Competition Experiments among 1ꢀ4, with NISa
(8) (a) In our group, this procedure had been applied to the cleavage
of a CꢀTMS bond arising from a Si-tethered RCM: Rodrı
´
guez-Escrich,
C.; Urpı, F.; Vilarrasa, J. Org. Lett. 2008, 10, 5191. For similar
´
applications: (b) Xie, Q.; Denton, R. W.; Parker, K. A. Org. Lett.
2008, 10, 5345. (c) Martin, D. B. C.; Vanderwal, C. D. J. Am. Chem. Soc.
2009, 131, 3472. For very recent I/TMS exchanges, see: (d) Herrmann,
A. T.; Martinez, S. R.; Zakarian, A. Org. Lett. 2011, 13, 3636. (e) Parker,
K. A.; Denton, R. W. Tetrahedron Lett. 2011, 52, 2115. Also see:
(f) Pawluc, P.; Franczyk, A.; Walkowiak, J.; Hreczycho, G.; Kubicki,
M.; Marciniec, B. Org. Lett. 2011, 13, 1976. (g) Denmark, S. E.; Muhuhi,
J. M. J. Am. Chem. Soc. 2010, 132, 11768. (h) Pawluc, P.; Madalska, M.;
Hreczycho, G.; Marciniec, B. Synthesis 2008, 3687.
a NMR chemical shifts are given in CDCl3 (the spectrawere registered
in CDCl3 and in 1:1 HFIP/CDCl3). The competition experiments were
carried out in 1:1 HFIP/CDCl3.
(9) In standard solvents such as CH3CN or in CH2Cl2, the outcomes
were worse.
(10) Commercial samples that were yellow or red were purified by
recrystallization from 1,4-dioxane/CCl4. See: Djerassi, C.; Lenk, C. T.
J. Am. Chem. Soc. 1953, 75, 3493.
However, with samples containing oxygen functional
groups and/or other double bonds conjugated with the
vinyl-TIPS group, the treatment with NIS gave moderate
yields and several byproducts, even in HFIP.9
Addition of 1 equiv of 2,6-lutidine7 did not prevent the
appearance of several spots on TLC. Even at 0 °C under
Ar, with pure NIS (white),10 protecting the vial from the
light, the solution turned pink after few minutes and
(11) For the most simple cases, the addition of Agþ was not crucial, as
mentioned (the reaction solutions turned pink, but very small amounts
of byproducts were formed).
(12) (a) Dolenc, D. Synlett 2000, 544. (b) Rai, A. Synlett 2008,
784 and references cited therein. NISac has not been used in
iododesilylations.
(13) Orazi, O. O.; Corral, R. A.; Bertorello, H. E. J. Org. Chem. 1965,
30, 1101. An exhaustive SciFinder search indicates that DIH has not
been used as a iododesilylating reagent (N-iodophthalimide either).
(14) (a) Creighton, J. A.; Haque, I.; Wood, J. L. Chem. Commun.
ꢁ
1966, 229. (b) Barluenga, J.; Gonzalez, J. M.; Campos, P. J.; Asensio, G.
Angew. Chem. 1985, 97, 341. (c) Barluenga, J.; Alvarez-Garcıa, L. J.;
Gonzalez, J. M. Tetrahedron Lett. 1995, 36, 2153. (d) Barluenga, J.;
´
(5) There is only one related example, the desilylation of 2-TIPS-2-
cyclopentenone with ICl. See: Davie, C. P.; Danheiser, R. L. Angew.
Chem., Int. Ed. 2005, 44, 5867.
ꢁ
ꢁ
a, L. J.; Gonzalez, J. M.; Campos, P. J.; Dıaz,
´ ´
Llorente, I.; Alvarez-Garcı
M. R.; Garcıa-Granda, S. J. Am. Chem. Soc. 1997, 119, 6933. (e) Also see
´
(6) The desilylation of ArSiR3 (ipso-SEAr) is well-known, however.
(7) Ilardi, E. A.; Stivala, C. E.; Zakarian, A. Org. Lett. 2008, 10, 1727.
For previous procedures, see references cited therein.
ref 8h and references cited therein.
(15) Also with Ipy2BF4, the use of HFIP was crucial to achieve high
yields of the desired iodo derivative in relatively short reaction times.
Org. Lett., Vol. 13, No. 18, 2011
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