A direct functionalization of tertiary alkyl bromides with O-, N-, and C-nucleophiles

Article abstract of DOI:10.1016/j.tetlet.2007.06.091

Silver oxide used in stoichiometric amounts promoted the direct functionalization of tert-alkyl bromides and provided the desired adducts in 39-96% isolated yield. Reaction of tert-bromides with carboxylic acids yielded esters, with alcohols and phenols yielded alkyl and aryl ethers, with amines and anilines yielded selectively mono-alkylated amines and anilines, and with a C-nucleophile yielded an all-carbon quaternary hydrocarbon. The method was applied to a sequential alkylation of a primary amine with two different alkyl bromides yielding selectively a tertiary amine with three different substituents in one-pot.

Full text of DOI:10.1016/j.tetlet.2007.06.091

Tetrahedron Letters 48 (2007) 5761–5765
A direct functionalization of tertiary alkyl bromides
with O-, N-, and C-nucleophiles
Petr Vachal,* Joan M. Fletcher and William K. Hagmann
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, United States
Received 10 May 2007; revised 15 June 2007; accepted 18 June 2007
Available online 23 June 2007
Abstract—Silver oxide used in stoichiometric amounts promoted the direct functionalization of tert-alkyl bromides and provided the
desired adducts in 39–96% isolated yield. Reaction of tert-bromides with carboxylic acids yielded esters, with alcohols and phenols
yielded alkyl and aryl ethers, with amines and anilines yielded selectively mono-alkylated amines and anilines, and with a C-nucleo-
phile yielded an all-carbon quaternary hydrocarbon. The method was applied to a sequential alkylation of a primary amine with two
different alkyl bromides yielding selectively a tertiary amine with three different substituents in one-pot.
Ó 2007 Elsevier Ltd. All rights reserved.
R2
N
While the reactions of primary and secondary alkyl
halides with various nucleophiles are among the most
employed strategies in organic synthesis, an analogous
direct selective functionalization of tertiary alkyl halides
remains largely unexplored and certainly underutilized.
In addition to inherently poor reactivity of tertiary alkyl
halides, reaction selectivity is compromised by the prev-
alence of the SN1 mechanism, which typically involves a
rearrangement of the carbocation intermediates that
often yield inseparable mixtures of products. Examples
of truly selective direct derivatization of tert-alkyl
bromides are scarce.1 To this end, a limited number of
reports on direct derivatization of tert-alkyl bromides
assisted by silver oxide have been reported in the litera-
ture; however, the scope has been limited to a handful of
closely related examples of a reaction of carboxylic acids
and alcohols with tertiary a-bromoamides forming dep-
sipeptides,2 and a-alkyloxyamides,3,4 respectively, and a
reaction of carboxylic acids with tert-butyl bromide
forming tert-butyl carboxylates.5
R1
a
: Alkylation
R2
n
+ MeI
O
R3
O
N
O
R3
O
R2
N
b: SNAr
c: tert-Bromide
functionalization
+
Br
R3
OH
R2
O
+
N
HO
R3
F
O
R1 = o-
,
m-, or p
-substituent; R2, R3 = alkyl or H
Figure 1. Preparation of a-aryloxy-a,a-dimethylacetamides. a: Alkyl-
ation of a-aryloxy-a–methylacetamide with methyl halide; b: Nucleo-
philic aromatic substitution (SNAr) of aryl fluoride or chloride with
a-hydroxy-a,a-dimethylacetamides; c: Direct bromide substitution in
a-bromo-a,a-dimethylacetamide with phenols.
a-methylacetates may be feasible in some cases under
forcing conditions, the approach failed for all investi-
gated examples of the general substrate structure
depicted in Figure 1. Nucleophilic aromatic substitution
(SNAr, method b): aryl fluorides and chlorides reacted
with sterically hindered a-hydroxy-a,a-dimethylacet-
amides but the scope was limited to examples of R1
being a strongly electron-withdrawing group(s) in p-
position and/or the left-hand side aromatic ring was het-
erocyclic. This method failed for all other aryl groups,
leaving a direct derivatization of tert-alkyl halides
(method c) as a viable option.
We became interested in the direct functionalization of
tert-alkyl halides when faced with the challenge of syn-
thesizing a class of a-(phenyloxy)-a,a-dimethylacet-
amides (Fig. 1). First, we considered synthetic strategies
other than a direct halide displacement. Direct alkyl-
ation (method a): while methylation of a-(phenyloxy)-
Keywords: Tertiary bromide; Silver oxide; Nucleophile; Steric hin-
drance; Quaternary.
*
Corresponding author. Tel.: +1 732 594 6624; fax: +1 732
5942210; e-mail: petr_vachal@merck.com
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.091

5762
P. Vachal et al. / Tetrahedron Letters 48 (2007) 5761–5765
Methods for nucleophilic displacement of tertiary alkyl
bromides with phenols using silver oxide in anhydrous
acetonitrile, previously published for carboxylic acids
and alcohols,2,3 failed to provide synthetically significant
yields of the desired products 3 but rather led to the for-
mation of a-methylacrylamides 4, the undesired byprod-
ucts resulting from HBr elimination (Table 1, entries 1–
3). We anticipated that the reaction solvent should play
a critical role, regardless whether the bromide displace-
ment proceeds via a charged, partially charged, or radi-
cal intermediate. We screened a variety of solvents in a
model reaction of phenol 1a and amide 2a, including
anhydrous DMF, NMP, THF, dichloromethane, ethyl
acetate, acetone, toluene, ether, and cyclohexane but
found no reaction rate acceleration or selectivity
improvement compared to anhydrous acetonitrile
(<10% of 3a was observed by HPLC in each case).
The key variable leading to an increased reaction rate
turned out to be presence of water in the reaction mix-
ture. When water was used as a co-solvent, a full conver-
sion of 2a was accomplished within practical reaction
time (entries 2 vs 5). In addition, a significant improve-
ment of the ratio of the desired product 3a versus the
undesired 4a (ratios 3/1 vs 7/1, respectively) was ob-
served as well as an increase in the overall reaction selec-
tivity against other byproducts, which effectively
increased the overall yield of the transformation (30%
vs 70% for entries 2 vs 5, respectively). The combination
of acetonitrile/water in a ratio of 95/5 proved superior
to combinations of all other investigated solvents with
water (entries 6 vs 7–10) as well as other acetonitrile/
water ratios.6
consistent with the results of an extensive screen of silver
salts outlined in Table 2. A panel of silver sources pro-
moted the desired model transformation of 2a to 3a with
variable rates and degrees of selectivity; in most cases,
elimination of HBr from 2a leading to 4a represented
the major reaction pathway (entries 5-9, 14). No salt
provided an advantage over oxide, confirming silver
oxide as a superior silver source for both activity and
chemo-selectivity (entries 1,2 vs 3–14).
Although conditions for the direct functionalization of
tert-alkyl bromide were optimized for a single pair of
substrates (1a and 2a; Table 1, entry 5), reaction rate
and selectivity enhancement allowed for its successful
application to a wide range of both nucleophiles (1)
and electrophiles (Table 3, 2).
Carboxylic acids as nucleophiles: Both aromatic and ali-
phatic carboxylic acids directly displaced tert-alkyl bro-
mide in model electrophile 2a providing respective esters
3b–3h in good overall isolated yield (Table 3).7 Although
ester formation using silver oxide has been previously
reported,2 the advantage of the partially aqueous condi-
tions reported here is an enhanced rate and higher
ratio of the desired 3b versus the undesired 4a resulting
in higher reaction yield. Compare, for example, data for
3b in Table 3 versus a ratio of 3b/4a = 10/1 and 60% iso-
lated yield of 3b for anhydrous acetonitrile. Although
the improvement resulting from water addition may
not seem as impressive in the case of 3b, it is absolutely
critical for 3c and 3h. While the products are not formed
under anhydrous conditions at all, our method provides
3c and 3h in excellent yields of 81% and 91%, respec-
tively, despite the extreme steric hindrance of both reac-
tant pairs. Electronic properties of the aromatic ring of
nucleophile 1 do not negatively affect the generality of
the transformation, for example, electron-deficient 3d
as well as electron-rich 3e–g acids directly displace
tert-alkyl bromide of 2a in good yields. Exclusive forma-
The increase in 3a/4a ratio and the overall reaction
selectivity may be explained by a close association of
all reaction partners in the key C–O bond forming step
in the model reaction of 1a with 2a. This would suggest
that the silver counter ion may play an important role in
the reaction rate and selectivity. The hypothesis proved
Table 1. Optimization of reaction solvent in the displacement of tertiary bromide of a model electrophile 2a with phenol (1a)
Ag2O, solvent
T(°C), time (h)
OPh
Br
+
+
PhOH
CONHBn
CONHBn
CONHBn
2a
1a
3a
4a
Entry
Solvent
T (°C)
Conv. of 2a,a rxn. time
3ab (%)
4ab (%)
Otherc (%)b
1
2
3
4
5
6
7
8
9
MeCNd
20
20
90
20
20
90
90
90
90
90
15% in 18 h
90% in 150 h
70% in 4 h
45% in 18 h
>90% in 48 h
>90% in 4 h
90% in 4 h
40% in 4 h
10% in 4 h
60% in 4 h
10
30
25
30
70
60
40
20
5
<5
10
10
5
10
10
15
20
5
5
40
35
10
15
15
35
<5
<5
30
MeCNd
MeCN
MeCN/H2Oe
MeCN/H2Oe
MeCN/H2Oe
Acetone/H2Oe
THF/H2Oe
DCM/H2Oe
DMF/H2Oe
10
<5
5
a HPLC conversion.
b HPLC yield.
c Other, unidentified byproducts.
d Entries 1 and 2 included for a side-by-side comparison to prior literature reports, see Refs. 2 and 3.
e Ratio of organic solvent/water = 95/5 (for other solvent ratios, see Ref. 6).

P. Vachal et al. / Tetrahedron Letters 48 (2007) 5761–5765
5763
Table 2. Optimization of silver counter ion in the displacement of tert-bromide of a model electrophile 2a with phenol (1a)
Silver(I)-salt
OPh
Br
MeCN/H2O (95/5)
+
+
PhOH
Conditions
A: 20 °C, 18 h; or
B: 90 °C, 4 h
CONHBn
CONHBn
CONHBn
2a
1a
3a
4a
Entry
Silver(I)-salt
Rxn cond.a
Conv. of 2ab (%)
3ac (%)
4ac (%)
Otherd (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ag2O
Ag2O
Ag2S
A
B
B
B
B
B
B
B
B
A
A
B
B
B
45
>90
10
<5
30
20
40
>90
20
90
30
60
0
0
10
0
0
0
0
20
0
5
10
5
<5
10
20
40
90
20
5
10
15
5
0
10
0
0
0
Ag2Se
Ag2CO3
AgOAc
AgOTf
AgOMs
AgSbF6
AgF
AgHF2
AgBr
AgI
0
70e
>90
5
<5
50
10
5
<5
40
30+50e
0
0
10
0
0
0
AgCN
a Reaction conditions, A: 18 h @ 20 °C, or B: 4 h @ 90 °C.
b HPLC conversion.
c HPLC yield.
d Other, unidentified byproducts.
e Major product N-benzyl a-fluoro-a,a-dimethylacetamide, which resulted from the displacement of bromide with fluoride; this observation is
consistent with the literature:11
tion of 3f demonstrates a complete selectivity of bromide
displacement with carboxylic acid in the presence of
unprotected phenol, which in turn may be subsequently
derivatized without protective group manipulation.
model secondary amide 2a, the tert-alkyl bromides of
primary (2b) and tertiary (2c) amides are also displaced
with benzoic acid yielding the desired esters 3q and 3r,
respectively, in yields comparable to the secondary
amide 3b (Table 3). The formation of tertiary amide
3q is particularly important since authors of previously
published silver oxide-utilizing methodology postulated
that the reaction was fundamentally limited to protic
a-bromoamides (primary and secondary amides).2b,3b
Not only do aprotic amides readily undergo the trans-
formation under our conditions but the scope extends
beyond amides to other electrophiles. Of these, esters
are exemplified by the reaction of 2d to 3s, which has
been prepared in 89% yield. Even a fully unfunctional-
ized electrophile, tert-butyl bromide, underwent the
transformation, providing an easy access to tert-butyl
benzoate (3t). When alcohols are used as nucleophiles
instead of a carboxylic acid with tert-butyl bromide,
our method provides a convenient access to synthetically
valuable tert-butyl ethers derived from primary (3u) as
well as secondary (3v) alcohols. While the use of tert-
butyl bromide as an electrophile for the formation of
tert-butyl carboxylates has been previously reported,5
our method is the first example of a direct synthesis of
tert-butyl ethers.
Phenols and alcohols as nucleophiles: The scope of the
nucleophiles amenable to displace tert-bromide of 2a
extends beyond carboxylic acids. The formation of aryl
ethers 3i,j (Table 3) represents two examples of p- and
m-substituted phenol additions to 2a (Table 3; for
another phenol-derived example, see Table 1, entry 5).
Similarly, alcohol derived alkyl ethers exemplified by
3k are prepared under the same conditions.
Amines and anilines as nucleophiles: Both anilines and
primary amines undergo a selective reaction with
1 equiv of 2a providing exclusively secondary anilines
and amines devoid of over-alkylation (3l–n in Table 3).
It is noteworthy that the reaction conditions are so mild
that a typically labile boronic acid ester in 3m remains
intact providing an attractive handle for a subsequent
product derivatization. An example of a secondary
amine also undergoes the direct tert-bromide displace-
ment, albeit at elevated temperature, selectively yielding
a tertiary amine 3o.
C-nucleophile: An example of a carbon nucleophile
(ethyl acetoacetate) directly displacing tert-alkyl bro-
mide of 2a under the method’s reaction conditions pro-
vided an example of a hydrocarbon bearing an all-
carbon quaternary center directly adjacent to an all-car-
bon tertiary center in 3p (Table 3).
Cyclic tert-alkyl bromide electrophiles 2f,g are represen-
tatives of additional challenges compared to their acyclic
counterparts: 2f exemplifies a particularly sterically hin-
dered substrate undergoing the reaction with benzoic
acid, yielding 3w in 51% yield (Scheme 1). While the
tert-alkyl bromide in cyclohexane derivative 2g is
slightly less sterically hindered compared to its cyclo-
butane analog 2f, the potential for HBr elimination
from 2g is very high due to the energetically favored
Benzoic acid was utilized to explore the scope of electro-
philes suitable for the transformation. In addition to the

5764
P. Vachal et al. / Tetrahedron Letters 48 (2007) 5761–5765
Table 3. Substrate scope of the direct functionalization of tert-alkyl bromides with O-, N-, and C-nucleophiles
Ag2O
MeCN/H2O
(95/5)
R1
Br
X
+
+
R1XH
T(°C), t(h)
R2
R2
R2
2a, R2 = -CONHBn
2b, R2 = -CONH2
2c, R2 = -CONBn2
2d, R2 = -CO2Bn
2e, R2 = -Me
1
3
4
-XH = -COOH
-XH = -OH
R1X- = R1O-
R1X- = R1COO-
R1X- = R1N(R3)-
R1X- = R1C(Ac)-
-XH = -N(R3)H
-XH = -C(Ac)H
3
R1
–X–
R2
T (°C)
t (h)
3/4a
3b (%)
3b
3c
3d
3e
3f
Ph
–COO–
–COO–
–COO–
–COO–
–COO–
–COO–
–COO–
–O–
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONHBn
–CONH2
–CONBn2
–CO2Bn
20
20
20
60
100
20
20
20
20
60
60
20
20
60
60
20
60
100
20
60
60
5
2
15
5
>50/1
30/1
40/1
>50/1
>50/1
>50/1
>50/1
>50/1
30/1
74
81
70
51
74c
70
91
63
72
81
96
55
72
48
39d
77
62
89
73
61
58
2,4,6-Me3–C6H2–
4-CN–C6H4–
4-(Me2N)-C6H4–
4-HO–C6H4–
4-MeO–C6H4–
tert-Bu–
3-Cl–C6H4–
4-CF3–C6H4–
PhCH2–
2
3g
3h
3i
10
12
15
16
4
5
20
1
2
24
2
36
24
2
3j
–O–
–O–
–NH–
3k
3l
12/1
Ph–
>50/1
>50/1
>50/1
>50/1
8/1
n.d.
8/1
15/1
n.d.
3m
3n
3o
3p
3q
3r
3s
3t
4-(4,4,5,5-Me4-1,3,2-dioxaborolan-2-yl)–C6H4–
–NH–
–NH–
–N–
–CH–
–COO–
–COO–
–COO–
–COO–
–O–
PhCH2–
PhCH2–(X)–CH2Ph
Ac-(X)–CO2Et
Ph–
Ph–
Ph–
Ph–
PhCH2–
Ph2CH–
–Me
–Me
–Me
3u
3v
4
8
n.d.
n.d.
–O–
a Ratio of 3/4 in the crude reaction mixture @ > 95% conversion of 2.
b Isolated yield of analytically pure product 3 (see Supplementary data for full characterization).
c Ester as the sole product resulting from selective reaction of the carboxylic acid functionality, no arylether was detected in the crude reaction
mixture.
d C-alkylation product; approx. 5% of O-alkylated product observed in the crude reaction mixture and separated from the desired C-alkylated
product by column chromatography on silica gel.
Ag2O
vided a basis for a one-pot tertiary amine synthesis de-
MeCN/H2O
(95/5)
picted in Scheme 2. Benzylamine was treated with
silver oxide and 2a, the first of two electrophiles. After
the first alkylation was completed (in 4 h at 20 °C in this
case by LCMS), a second electrophile, allyl bromide,
was added to the reaction mixture. After the second
alkylation was completed (in 24 h at 60 °C in this case
by LCMS), the reaction mixture was simply filtered
and purified yielding amine 3y in 55% overall yield via
a single-pot procedure. We believe that this approach
represents a particularly attractive facile strategy for
the preparation of differentially substituted tertiary
amines, which would otherwise require a multi-step syn-
thetic effort and protection group manipulations to
avoid bisalkylation with one of the two electrophiles.
O
+
PhCO2H
PhCO2H
Ph
O
CO2Et
100
CO2Et
°C, 10 h
Br
2f
3w, 51%
Ag2O
MeCN/H2O
(95/5)
O
+
Ph
O
CONHBn
60 °C,
2 h
Br
CONHBn
2g
3x, 41%
Scheme 1. Direct functionalization of tert-alkyl bromide with benzoic
acid: examples of cyclic electrophiles.
endo-ene 1-cyclohexene-1-carboxamide. Even though
the elimination of HBr does occur and actually accounts
for approximately half of the starting material conver-
sion, the desired ester 3x is still isolated in a practical
41% yield.
1. 2a, 20
°C, 4 h
2. CH2=CHCH2Br, 60
°C, 24h
Ph
N
CONHBn
3y, 55%
Ph
NH2
Ag2O, MeCN/H2O (95/5)
one-pot
The selectivity observed for the alkylation of primary
and secondary amines yielding exclusively secondary
and tertiary amines, respectively (3l–o Table 3), pro-
Scheme 2. One-pot selective formation of tertiary amine bearing three
different substituents.

P. Vachal et al. / Tetrahedron Letters 48 (2007) 5761–5765
5765
From a mechanistic stand point, it is remarkable that
Supplementary data
the enormous rate acceleration and increased selectivity
for the desired adducts 3 over undesired byproducts 4
reported therein is caused solely by the presence of water
in the reaction media (Table 1, entries 1 vs 4). This phe-
nomenon may possibly be explained by the relative in-
crease of the homogeneous character of silver oxide.
Although solubility/hydration of silver oxide in aqueous
media is low,8 it generally exceeds the solubility in or-
ganic solvents. This may result in an increase in the rel-
ative activity of silver oxide due to an increased partition
coefficient of silver ions between the liquid versus solid
states effectively resulting in the observed rate enhance-
ment.9 Alternatively, the rate acceleration may be ex-
plained by the increased concentration of the free
hydroxide anion resulting from the elevated soluability
of silver oxide. A free hydroxide anion may increase
the nucleophilicity of R–X–H by its partial deprotona-
tion, an idea entertained by kinetic studies of related
silver-promoted reactions.10 This notion would be
supported by the failure of alternate silver sources to
promote the desired transformation as they could not
generate hydroxide anion in solution (Table 2) and ex-
plain the selectivity observed for 2f!3f (Table 3). While
nucleophile deprotonation may be an important con-
tributing factor to reactions of some R–X–H nucleo-
philes such as phenols and ethyl acetoacetate, it is
unlikely to explain the increased reactivity of others,
such as alcohols and amines, for which hydroxide anion
is outside of the range needed for any appreciable
amount of nucleophile deprotonation. Furthermore,
no selectivity for the alkylation of carboxylic group over
aniline was observed in case of 4-aminobenzoic acid
(such selectivity should be expected based on analogy
to 2f!3f should deprotonation be critical). In addition
to the rate enhancement of the reaction, an increased
selectivity of the reaction in partially aqueous media
versus anhydrous conditions is consistent with a tighter
association of the silver ion in the bond-forming event of
the reaction coordinate either in a transition state or a
discrete intermediate complex.
Full experimental procedures and compound character-
ization by NMR and LCMS, and HRMS analyses; a
1
copy of H and 13C NMR and LCMS is provided for
all final compounds. Supplementary data associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2007.06.091.
References and notes
1. For a recent review, see: Peters, K. S. Acc. Chem. Res.
2007, 40, 1.
2. (a) Caviccioni, G. Tetrahedron Lett. 1987, 28, 2427; (b)
Gavicchioni, G.; D’Angeli, F.; Casolari, A.; Orlandini, P.
Synthesis 1988, 947.
3. (a) Catelani, G.; Nejad, F. M. K.; D’Angeli, F.; Cavic-
chioni, G.; Marchetti, P. Gazz. Chem. Ital. 1992, 122, 51;
(b) Cavicchioni, G. Synth. Commun. 1994, 24, 2223.
4. A single example of a phenol addition has been reported in
ref. 2b yielding the desired a-phenoxyamide in 50% yield
in 3 days. We were unable to reproduce this result; please
see Table 1 for details.
5. (a) Okamoto, K.; Watanabe, M.; Kawada, M.; Goto, G.;
Ashida, Y.; Oda, K.; Yajima, A.; Imada, I.; Morimoto, H.
Chem. Pharm. Bull. 1982, 30, 2797; (b) Arnold, Z.
Synthesis 1990, 39; (c) Georgiadis, D.; Matziari, M.;
Vasiliou, S.; Dive, V.; Yiotakasis, A. Tetrahedron 1999, 55,
14635; (d) Lemek, T.; Makosza, M.; Golinski, M. Tetra-
hedron 2001, 57, 4753.
6. While the selectivity and the rate of the model reaction
remained unchanged with increasing water content, aque-
ous fraction significantly higher then 5% of the reaction
media caused precipitation of 2a and 3a. For practical
applications, acetonitrile/water ratio of 95/5 proved
optimal.
7. A typical experimental procedure: To a mixture of
nucleophile 1 (100 mg) and electrophile 2 (0.5 equiv of
2a–d or 4 equiv of 2e) in acetonitrile (2 mL) and water
(0.1 mL), silver oxide (2 equiv) is added in one portion.
The resulting heterogeneous reaction mixture is stirred at
temperature and for time indicated in Table 3 while
monitored by LCMS for conversion of the limiting
reagent. The crude reaction mixture is filtered through a
disposable frit and solids rinsed with ethyl acetate (2 mL).
The combined filtrates are concentrated and subsequently
purified either by column chromatography on silica gel
(eluent: hexanes/ethyl acetate) or by preparative reverse
phase HPLC to afford 3 in isolated yield indicated in Table
3. See the Supplementary data for full experimental details
and characterization of all products by 1H and 13C NMR,
LCMS, and HRMS.
In conclusion, we have identified a general strategy for a
direct functionalization of tert-alkyl bromides. The
method is applicable to a variety of electrophiles includ-
ing protic and aprotic amides, esters as well as com-
pletely unfunctionalized alkyl bromides. These
electrophiles undergo a bromide displacement with a
wide range of nucleophiles including O-nucleophiles
such as carboxylic acids, phenols, and alcohols, N-
nucleophiles, such as anilines and amines, and even C-
nucleophiles exemplified by ethyl acetoacetate.
8. Water solubility of silver oxide is 13 mg and 60 mg in
100 mL of cold and warm water, resp.: Handbook of
Chemistry and Physics, 73rd ed.; Lide, D. R., Ed.; Boca
Raton: FL, 1993.
9. (a) Dirkse, T. P. Sol. Data Ser. 1986, 23, 83; (b)
Morimoto, T.; Aoki, K. Langmuir 1986, 2, 525.
10. For an exceptional review, see: The Chemistry of Halides,
Pseudo-halides and Azides; Patai, S., Rappoport, Z., Eds.;
John Willey & Sons: Chichester, 1983, Supplement D, Part
2.
Acknowledgments
The authors would like to gratefully acknowledge Dr. V.
Colandrea for valuable discussions and Dr. B. Choi for
performing HRMS of compounds 3a–3y.
11. Kaselj, M.; Gonikberg, E. M.; LeNoble, W. J. J. Org.
Chem. 1998, 63, 3218.