Zinc-mediated synthesis of tertiary alkyl selenides from tertiary alkyl halides

Article abstract of DOI:10.1055/s-2005-918933

Diorganyl selenides are efficiently synthesized from tertiary alkyl halides, selenols or selenolates and zinc dibromide as well as from diselenides in the presence of zinc. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-918933

2832
LETTER
Zinc-Mediated Synthesis of Tertiary Alkyl Selenides from Tertiary Alkyl
Halides
Z
inc-Mediated Syn
l
thesis
a
of Tertiary
iAlkyl Sn
elenides Krief,*a Michel Derock,a,b Damien Lacroixa,b
a
Laboratoire de Chimie Organique de Synthèse, Facultés Universitaires N.-D. de la Paix, 61 rue de Bruxelles, Namur 5000, Belgium
Fax +32(0)81724536; E-mail: alain.krief@fundp.ac.be
b
Fonds pour la Formation à la Recherche dans l’Industrie et l’Agriculture, 5 rue d’Egmont, Bruxelles 1000, Belgium
Received 28 July 2005
of 2-methyl-2-phenylseleno-undecane (1ca) in very good
yield and with no trace of 6a or 6b (Equation 1, entry b).
Abstract: Diorganyl selenides are efficiently synthesized from
tertiary alkyl halides, selenols or selenolates and zinc dibromide as
well as from diselenides in the presence of zinc.
Related substitution reactions have been observed when
tert-butyl iodide (3b1) was reacted, under similar condi-
tions, with sodium phenylselenolate 4a or decylselenolate
4b (Equation 2).
Key words: substitution, alkyl halides, diorganyl selenides
The synthesis of tertiary alkyl selenides 1 by substitution
on a tertiary alkyl group is not an easy task. Nevertheless,
it has been achieved from (i) tertiary alcohols and selenols
2 in the presence of protic- (H2SO4) or Lewis acids
(ZnCl2),1 (ii) 1-iodo adamantane (3a1) and sodium phe-
nylselenolate (4a) in the presence of light,2 and (iii) more
recently on reaction of tert-butyl halides 3b, diphenyl-
diselenide (5a) and indium(I) iodide.3
1 equiv ZnBr2, toluene, 20 °C, 20 h
t-Bu-I + RSeNa
3b1
4a PhSeNa
n-DecSeNa
t-BuSeR
1
4
1ba 90%
80%
4b
1bb
Equation 2 Synthesis of tert-butyl selenides from sodium
selenolates in the presence of zinc dibromide
Although alkali metal selenolates 4 have been routinely
used to produce selenides from primary and secondary
alkyl, benzyl and allyl halides, there is, to our knowledge,
no report concerning related tertiary alkyl halides 3.
Although selenols 2 were expected to allow a more
straightforward approach to 1, we found that butylation of
toluene leading to 7, competes with the desired reaction
when it is carried out in the presence of zinc dibromide
(Equation 3, entry a). However, use of dichloromethane
instead of toluene precludes the Friedel–Crafts reaction
and leads to tert-butyl selenides 1b and 1d in good yields
from tert-butyl iodide (3b1, Equation 3, entries b, c).
We now report that sodium phenylselenolate (4a) in DMF
reacts with 2-bromo-2-methyl undecane (3c2) to produce,
in 91% overall yield, an 81:19 mixture of 2-methyl-2-un-
decene (6a) and 2-methyl-1-undecene (6b) resulting from
Saytzeff and Hofmann elimination reactions, respectively
(Equation 1, entry a).4
1 equiv ZnBr2, toluene,
a
t-Bu-SePh + t-Bu
1ba 61 %
Me
1 equiv PhSeNa 4a, DMF,
+
20 °C, 20 h
a
Oct
Oct
20 °C, 1 h
91% (6a:6b 81:19)
t-Bu-I + RSeH
3b1
7 17 %
6a
6b
2
Br
1 equiv ZnBr2, CH2Cl2 20
°C, 5 h
Oct
3c2
t-Bu-SeR
SePh
b
1 equiv PhSeNa 4a, 1 equiv ZnBr2,
toluene, 20 °C, 2.5 h
80 %
1ca
Oct
b
c
2a PhSeH
n-DecSeH
1ba 90 %
1bb
70 %
2b
Equation 3 Substitution of tert-alkyl halides by selenols using zinc
dibromide
Equation 1 Synthesis of tert-alkyl selenides by substitution of tert-
alkyl halides by sodium phenylselenolate in the absence and in the
presence of zinc dibromide
However, this reaction proceeds with neither primary nor
secondary alkyl bromides.
Performing the reaction between 3c2 and 4a in toluene
in the presence of one equivalent of zinc dibromide
dramatically changes its course and allows the synthesis
An even more expedient route to tert-alkyl selenides 1
involves mixing tertiary alkyl halides 3, diorganyl di-
selenides 5, and zinc in dichloromethane (used as the
solvent; Equation 4, Table 1).5 The reaction proceeds in-
distinctly, with tertiary butyl iodide, bromide and chloride
at room temperature in five hours (Table 1, entry a–c).
SYNLETT 2005, No. 18, pp 2832–2834
0
3
.1
1
.2
0
0
5
Advanced online publication: 12.10.2005
DOI: 10.1055/s-2005-918933; Art ID: G24205ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Zinc-Mediated Synthesis of Tertiary Alkyl Selenides
2833
CH2Cl2
The methods of syntheses of tertiary alkyl selenides just
disclosed apparently proceed by different mechanisms al-
though they apply to the same type of carbon frameworks
with apparently the same generality and limitations and
might involve zinc selenolates. In the two former methods
zinc dibromide can act as a Lewis acid catalyst but the
intermediate formation of zinc selenolates cannot be ex-
cluded, especially when the reaction is carried out with so-
dium selenolates and zinc dichloride (Equation 1, entry
b). Related reactions, whose mechanisms have never been
explicated, have been already successfully achieved with
azide,6a water,6b acetates,6c,d thiolacetates6e or thiocyan-
ates,6f as their zinc salts or in the presence of zinc salts.
R1-SeR
R1-X + 0.5 equiv RSeSeR + 0.5 equiv Zn
Conditions
3
5
1
Equation 4 Synthesis of tert-alkyl selenides from tert-alkyl
halides, diorganic diselenides, and zinc
It takes place with equal success with a large variety of
tertiary alkyl halides including 1-bromo adamantane (3a2)
(Table 1, entries e, k, l) and diselenides 5 such as diphe-
nyl-5a (Table 1, entries a–e, m–o), dimethyl-5c (Table 1,
entry f), straight dialkyl chains such as di(n-butyl)-5d and
di(n-decyl)-5b (Table 1, entries g, h, k, l), branched di-
alkyl chains such as di(s-butyl)-5e (Table 1, entry i),
dibenzyl-5f (Table 1, entry j) diselenides.
The reaction involving tertiary alkyl halides, diorganyl
diselenides and elemental zinc seems to be unprecedented
although the reaction of alkyl halides, diorganyl dise-
lenides and elemental zinc has been already described.7,8
For example, several alkyl-, allyl-, and benzyl selenides,
including functionalized ones have been synthesized in
good yields from the corresponding alkyl halides, diphe-
nyl diselenide 5a and zinc dust in aqueous acetonitrile7,8
containing in some case phosphates.7 However, it has
been reported that under these conditions primary and
secondary alkyl halides deliver the corresponding phenyl
selenide in up to 90% yield whereas tert-butyl iodide
(3b1), -bromide (3b2), and 1-iodo adamantane (3a1)
produce the corresponding phenyl selenides in very poor
yields (0–16%).7
Surprisingly, in the case of 1-bromo-adamantane (3a2) the
reaction proceeds faster with diphenyldiselenide than
with di(n-butyl) diselenide (Table 1, compare entries e, k,
l) although both diselenides react with almost the same
rate with tert-butyl iodide (3b1, Table 1, entries a, g).
The reaction does not proceed under these conditions with
n- and s-alkyl halides such as 1-bromodecane and 2-
bromooctane; iodobenzene and tert-butyl acetate but
takes place with primary benzyl halides 3d (Table 1, en-
tries m–o). In such case and contrary to what we have
observed with tert-butyl halides 3b, there is an important
difference of reactivity between the bromide 3d2 and
the chloride 3d3 (Table 1, entries m–o, compare to entries
b, c).
Table 1 Synthesis of Tertiary Alkyl Selenides 1 from Diorganic Diselenides 5 and Tertiary Alkyl Halides 3
Entry
Diselenides (R)
5
Alkyl halide
3
Conditions
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 5 h
20 °C, 96 h
45 °C, 24 h
20 °C, 5 h
20 °C, 5 h
20 °C, 24 h
1
Yield of 1 (%)
a
b
c
d
e
f
Ph
5a
5a
5a
5a
5a
5c
5d
5b
5e
5f
tert-Butyl iodide
tert-Butyl bromide
tert-Butyl chloride
2-Bromo-2-methyl undecane
1-Bromo adamantane
tert-Butyl iodide
tert-Butyl iodide
tert-Butyl iodide
tert-Butyl iodide
tert-Butyl iodide
1-Bromo adamantane
1-Bromo adamantane
Benzyl bromide
3b1
3b2
3b3
3c2
3a2
3b1
3b1
3b1
3b1
3b1
3a2
3a2
3d2
3d3
3d3
1ba
1ba
1ba
1ca
1aa
1bc
1bd
1bb
1be
1bf
1ad
1ad
1da
1da
1da
87
89
86
87
95
80
70
90
70
90
63
80
91
57
83
Ph
Ph
Ph
Ph
Me
n-Bu
n-Dec
s-Bu
Bn
g
h
i
j
k
l
n-Bu
n-Bu
Ph
5d
5d
5a
5a
5a
m
n
o
Ph
Benzyl chloride
Ph
Benzyl chloride
Synlett 2005, No. 18, 2832–2834 © Thieme Stuttgart · New York

2834
A. Krief et al.
LETTER
(4) Carey, F. A.; Sunberg, R. J. In Advanced Organic
Our method is unique since it takes only place in nonpolar
solvents such as dichloromethane and, at the difference of
all those reported so far7–10 including those involving in
situ reduction of diphenyl diselenide with zinc,7,8
lanthanum9 or indium iodide,3 it is very selective for
tertiary alkyl halides and does not proceed with primary
and secondary alkyl halides.11 Those are inert under our
experimental conditions and are recovered unchanged
from the reaction medium even after prolonged reaction
time.
Chemistry, Parts A and B; Kluwer Academic Plenum
Publishers: New York, 2000.
(5) (a) A solution of 2-bromo-2-methyl-undecane (1.24 g, 5
mmol) in anhyd CH2Cl2 (3 mL) was added at r.t., to a
suspension of zinc (327 mg, 5 mmol) and diphenyldiselenide
(780 mg, 2.5 mmol) in CH2Cl2 (2 mL). The suspension was
stirred at r.t. for 5 h. Then, H2O (10 mL) was added and the
mixture wasextracted with Et2O (3 × 25 mL) and washed
with H2O (3 × 20 mL). The ether layer was dried by MgSO4
and evaporated to give an oily residue, which on purification
by column chromatography (SiO2, pentane) afforded pure 2-
methyl-2-phenylseleno undecane: 1.42 g, 4.37 mmol, 87%
yield. (b) Spectroscopic data: IR, 1H NMR and 13C NMR,
MS agree with the proposed structures. Microanalyses of
novel compounds agree with the calculated values.
(6) (a) Miller, J. A. Tetrahedron Lett. 1975, 2959.
(b) Anandaraman, S.; Gurudutt, K. N.; Nataradjan, C. P.;
Ravindranath, B. Tetrahedron Lett. 1980, 21, 2189.
(c) Gurudutt, K. N.; Ravindranath, B.; Srinivas, P.
Tetrahedron 1982, 38, 1843. (d) Ravindranath, B.; Srinivas,
P. Tetrahedron 1984, 40, 1623. (e) Gurudutt, K. N.; Rao, S.;
Srinivas, P.; Srinivas, S. Tetrahedron 1995, 51, 3045.
(f) Gurudutt, K. N.; Rao, S.; Srinivas, P. Indian J. Chem.,
Sect. B: Org. Chem. Incl. Med. Chem. 1991, 30, 343.
(7) Bieber, L. W.; de Sa, A. C. P. F.; Menezes, P. H.; Gonçalves,
S. M. C. Tetrahedron Lett. 2001, 42, 4597.
This reaction involves a zinc-mediated reduction, which is
expected to occur via a stepwise two-electron transfer
mechanism. Surprisingly, however, zinc neither reacts
with diselenides 5 in the absence of tertiary alkyl halides
3 nor with the tertiary alkyl halides 3 when diselenides 5
are missing. Another interesting observation is that both
seleno moieties present on the diselenide generate the
tertiary alkyl selenides 1.
Anyhow, as a proof of the value of this new method, we
have been able to substitute chemoselectively the bromide
attached to the tertiary alkyl group present in 3e leaving
the primary one unaffected (Equation 5).5
(8) Movassagh, B.; Shamsipoor, M. Synlett 2005, 121; and
references cited therein.
CH2Cl2
+ 0.5 equiv PhSeSePh
Br
1ka 80%
Br
+ 1 equiv Zn
25 °C, 5 h
(9) Nishino, T.; Okoda, M.; Kuroki, T.; Watanabe, T.;
Nishiyama, Y.; Sonoda, N. J. Org. Chem. 2002, 67, 8696.
(10) (a) Rheinboldt, H. Schwefel-, Selen-, Tellur-Verbindungen,
In Methoden der organische Chemie (Houben–Weyl), Vol.
9; Müller, E., Ed.; Georg Thieme: Stuttgart, 1967.
(b) Organic Selenium Compounds: Their Chemistry and
Biology; Klayman, D. L.; Gunther, W. H. H., Eds.; John
Wiley and Sons: Chichester, 1973. (c) Paulmier, C. In
Selenium Reagents and Intermediates in Organic Synthesis,
Vol. 5; Baldwin, J. E., Ed.; Pergamon: Oxford, 1986.
(d) The Chemistry of Organic Selenium and Tellurium
Compounds, Vol. 2; Patai, S.; Rappoport, Z., Eds.; John
Wiley and Sons: Chichester, 1987. (e) Krief, A.; Hevesi, L.
In Organoselenium Chemistry, Vol. 1; Springer Verlag:
Berlin, 1988. (f) Krief, A. In Comprehensive
PhSe
Br
3e
5a
Equation 5 Selective substitution of a tertiary alkyl halide in the
presence of a secondary alkyl halide
We are working in order to extend the scope of this reac-
tion to chemical substances bearing other functional
groups.
References
(1) Clarembeau, M.; Krief, A. Tetrahedron Lett. 1984, 25, 3625.
(2) (a) This reaction produces, besides phenyl 1-adamantyl
selenide (62%), diphenyl selenide (13%) as well as di(1-
adamantyl) selenide (14%). (b) Palacios, S. M.; Alonso, R.
A.; Rossi, R. A. Tetrahedron 1985, 41, 4147. (c) Phenyl 1-
adamantyl selenide has also been synthesized in poor yield
via an SH2 process from adamantane-1-carboxylic acid, lead
tetracetate and diphenyl selenide,2d or in good yield from 1-
adamantyl trifluoroacetate and phenyl selenol.2d
(d) Perkins, J.; Turner, E. S. J. Chem. Soc., Chem. Commun.
1981, 139.
Organometallic Chemistry II, Vol. 11; Abel, E. W.; Stone, F.
G. A.; Wilkinson, G.; McKillop, A., Eds.; Pergamon:
Oxford, 1995, 516. (g) Gladysz, J. A.; Hornby, J. L.; Garbe,
J. J. Org. Chem. 1978, 43, 1204.
(11) As pointed out by a referee ‘an apparent similar reaction was
reported recently in the same journal’.8 The reaction
proceeds in polar solvent and has a completely different
outcome than that reported in this paper: in MeCN–H2O it
gives a different result, demonstrating no significant reaction
with tertiary alkyl halides and facile reaction with primary
and secondary halides. We are working in order to
understand this spectacular solvent effect; less basic solvents
usually favor SN1-type reaction.
(3) (a) Ranu, B. C.; Mandal, T.; Samanta, S. Org. Lett. 2003, 5,
1439. (b) Ranu, B. C.; Mandal, T. J. Org. Chem. 2004, 69,
5793.
Synlett 2005, No. 18, 2832–2834 © Thieme Stuttgart · New York