[HP(HNCH2CH2)3N]NO3: An efficient homogeneous and solid-supported promoter for aza and thia-Michael reactions and for Strecker reactions

Article abstract of DOI:10.1016/j.tet.2005.09.117

In the presence of a catalytic amount of an azaphosphatrane nitrate salt, amines and thiols react readily with Michael acceptors. The salt is also an efficient promoter for the one pot synthesis of α-amino and α-amidonitriles. By anchoring the salt to Merrifield Resin, a reusable heterogeneous catalyst is obtained for these reactions. Evidence is presented for catalysis being attributable solely to the NO₃^- ion.

Full text of DOI:10.1016/j.tet.2005.09.117

Tetrahedron 62 (2006) 440–456
[HP(HNCH2CH2)3N]NO3: an efficient homogeneous and
solid-supported promoter for aza and thia-Michael reactions
and for Strecker reactions
*
Brandon M. Fetterly, Nirmal K. Jana and John G. Verkade
Department of Chemistry, Iowa State University, 1605 Gilman Hall, Ames, IA 50011, USA
Received 1 July 2005; revised 6 September 2005; accepted 16 September 2005
Available online 21 November 2005
Abstract—In the presence of a catalytic amount of an azaphosphatrane nitrate salt, amines and thiols react readily with Michael acceptors.
The salt is also an efficient promoter for the one pot synthesis of a-amino and a-amidonitriles. By anchoring the salt to Merrifield Resin, a
reusable heterogeneous catalyst is obtained for these reactions. Evidence is presented for catalysis being attributable solely to the NOK3 ion.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
by acylation of an a-aminonitrile.15b,c,16,17a–e,18,19 Strecker
reactions are generally carried out in aqueous solution with
a variety of cyanide ion sources, including trimethylsilyl
cyanide (TMSCN),17 which appears to be most useful and
also relatively safe.
The Michael conjugate addition reaction has been a useful
tool for organic, medicinal, and biochemists for several
decades.1 This transformation is an efficient and commonly
used route to the formation of C–C,2 C–O,3 C–N,4 and C–S5
bonds and it facilitates, for example, the synthesis of
important amino alcohols and versatile intermediates for a
large number of natural products,6 heterocycles,7 peptides,8
and chiral auxiliaries.9 Protected b-amino carbonyl
compounds and b-thiocarbonyl compounds can also be
prepared via aza-Michael and thia-Michael reactions,
respectively.10
A variety of homogeneous catalysts containing Lewis acidic
metal ions have been reported for the Strecker reac-
tion.15b,c,16b,17e,18a,c,e The Strecker reaction is also known
to proceed via the nucleophilic addition of cyanide to an
imine in the absence of a catalyst, albeit with long reaction
times (2–3 days).19 Many of the reported methodologies for
this reaction involve the use of relatively expensive
reagents, extended reaction times and/or tedious work-up
procedures leading to the generation of considerable
amounts of waste, which in a substantial number of
instances is toxic.
Michael reactions are facilitated homogeneously by protic
acid catalysts,11 base catalysts,2a,c,3 or Lewis acid
catalysts.4,5 Recently, bismuth nitrate4b and also palladium
tetrafluoroborate and chloride complexes4f have been
reported to catalyze the production of b-amino and b-thio
carbonyl compounds in the presence of a,b-unsaturated
ketones.
By contrast with a-aminonitriles, few reports were found
describing the preparation of a-amidonitriles.15 These two-
step methods require relatively long reaction times and
relatively tedious work-up procedures that generate
comparatively large quantities of toxic waste.15
a-Aminonitriles, often synthesized by a Strecker reaction,12
are highly useful synthons for the synthesis of a-amino
acids13 and nitrogen and sulfur-containing heterocycles14
such as imidazoles and thiadiazoles. Acyclic a-amido-
nitriles15 are versatile synthons for the synthesis of diverse
heterocyclic compounds,16 and they are normally prepared
Catalysts bound to cross-linked polystyrene solid supports
are well known and have been utilized for a myriad of
organic transformations.20 Azaphosphatrane 1a supported
on crosslinked polystyrene has been shown to be an
effective procatalyst in dehydrohalogenations and debromi-
nations with NaH.21 Acylation of alcohols has been
achieved using polymer-supported iminoproazaphospha-
trane 2.22
Keywords: Homogeneous; Heterogeneous; Catalysis; Michael reactions;
Nitrate; Azaphosphatrane; Promoter.
Corresponding author. Tel.: C1 515 294 5023; fax: C1 515 294 0105;
e-mail: jverkade@iastate.edu
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.117

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
441
Polymer-supported catalysts are also known to catalyze
Michael reaction such as acids,23 cinchona alkaloids,24
catalytic lithium and aluminum ions complexed by a ligand
linked to the polymer,2b or fluoride ion.25 Unfortunately,
these catalysts have only been tested on a small number of
amines. Moreover, repeated recycling of these polymers
was either not discussed or the polymer mounted catalysts
required periodic reactivation.
a,b-unsaturated nitriles. We also report here a simple one-
pot three-component protocol for the preparation of a
variety of a-aminonitriles using 1b28 as a promoter in
reactions wherein nitrate ion is demonstrated to be the
catalytically active species. A one-pot four-component
coupling method for the synthesis of a-amidonitriles using
1b is also reported.
Although resin bound catalysts for the Strecker reaction are
known, such catalysts either involve the use of toxic
metals26 or of multistep syntheses.27
2. Results and discussion
2.1. Homogeneously catalyzed Michael reactions
Initially, we attempted to use the deprotonated form of 1e
[i.e., P(MeNCH2CH2)3N] as a base catalyst for the aza-
Michael reaction of aniline with methyl vinyl ketone, but to
no avail. We found, however, that although 10 mol% of the
chloride salt 1f gave no detectable yield of product in this
reaction, 10 mol% of the nitrate salts 1e and 1g afforded a 78
and a 72% product yield after 30 h at room temperature,
respectively. Because 1b is considerably easier and cheaper
to synthesize than 1e or 1g, we continued our investigations
with 1b, which was prepared from commercially available
starting materials in a single step as shown in Scheme 1.
R
X
1a
1b
1c
1d
1e
1f
H
H
H
H
Me
ClK
NO3
CF3CO2
CF3CO3
NO3
Me2CHCH2
Me2CHCH2
Cl
NO3
When we screened the trifluoroacetate and triflate salts of 1b
(1c and 1d, respectively) in the reaction of aniline with
methyl vinyl ketone under the aforementioned conditions,
the reactions were quite slow, furnishing product yields of
70 and 72% after 40 h using 1c and after 48 h using 1d,
respectively. We also tested 10 mol% solution concen-
trations of HNO3, NaNO3, NaNO3 in the presence of 15-
crown-5, CAN, Bu4N(NO3), 1-butyl-3-methylimidazolium
chloride, and 1-ethyl-3-methylimidazolium nitrate in this
reaction, all of which provided unimpressive yields of 40,
32, 20, 0, 30, 45, and 50%, respectively, after 40 h. We
attribute these poor results to anion–cation interactions that
significantly exceed those experienced with the cation in 1b
wherein the positive charge is very well delocalized among
the phosphorus and the four nitrogens as can be envisioned
in the five resonance structures that can be drawn.
1g
Our interest in thia and aza-Michael reactions was piqued by
the efficacy of bismuth nitrate as a catalyst and particularly
by the apparent co-catalytic role of the nitrate ion.4b To
ensure that the nitrate ion in our experiments would be
essentially free of Lewis acid–Lewis base interactions with
its counter cation, in contrast to the likelihood of such
interactions between the bismuth(III) cation and nitrate ion,
we chose to investigate the nitrate salts of three aza-
phosphatranes, namely, 1b,e and 1g because of the
opportunity for positive charge delocalization in the
azaphosphatrane cations. Here, we report the synthesis of
these salts and compare their efficiencies as catalysts with
previously synthesized 1c,d, and 1f28 for the aza and thia-
Michael reactions of amines and thiols at room temperature
with a,b-unsaturated ketones, a,b-unsaturated esters and
In the presence of 10 mol% of 1b, reactions of methyl vinyl
ketone with the anilines in Table 1 (entries 1–5) gave
reasonable to good yields, except for relatively poorly
nucleophilic 3-nitroaniline, which contains the strongly
electron withdrawing nitro group. With morpholine and the
acceptors shown in entries 6–10 in Table 1, the correspond-
ing aza-Michael products were realized in good to excellent
yields. Piperidine and 1-aminonaphthalene when reacted
with methyl vinyl ketone, gave good yields of the expected
aza-Michael reaction product (Table 1, entries 10 and 11)
although the reaction involving 1-aminonaphthalene
Scheme 1. Synthesis of 1b.

442
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
required warming to 50 8C to accelerate the reaction.
Benzylamine and piperonylamine also participated well in
the aza-Michael reaction, giving the anticipated products in
excellent yields (entries 12 and 13 in Table 1).
Thiophenol when allowed to react with a variety of
acceptors in the presence of 10 mol% of 1b, afforded the
corresponding thia-Michael reaction products in excellent
yields after 40 h at room temperature (Table 2, entries 1–4).
Table 1. Room temperature aza-Michael reactions in the presence of 1b as a promotera
Entry
Donor
Acceptor
Time
(h)
Product
Yield w/o
cat. (%)b
Yield
w/1b (%)b
Lit. yield
(%)c
1
30
40
NR
78
68
80–904f
d
–
2
3
40
83
7310g
4
40
84
7610g
e
5
6
50
20
NR
40
27
90
–
87–884g,k
7
8
20
20
50
45
86
98
914g
824g
9
20
20
85
88
604j
10
40
87–904e,l
e
11
12
20
48
85f
–
70
98
60–704g,h,l

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
443
Table 1 (continued)
Entry
Donor
Acceptor
Time
(h)
Product
Yield w/o
cat. (%)b
Yield
w/1b (%)b
Lit. yield
(%)c
g
–
13
48
60
96
a Conditions: amine (2.0 mmol), acceptor (2.5 mmol), 1b (10 mol%) and CH3CN (3 mL).
b Isolated yields.
c Literature yields.
d This compound was reported earlier in Ref. 7b, but no yield was given.
e New compound.
f
Heated at 50 8C.
g Although this compound has been reported and characterized,4m its yield and NMR spectral data were not given.
Butanethiol also provided thia-Michael products in
excellent yields after 48 h (Table 2, entries 5–8).
case was the yield roughly the same as the minimum
literature yield.
Our protocol is simple and of good scope, giving product
yields that are better in 12 of the 17 reactions for which
literature yields could be found (as seen in Tables 1 and 2).
In three additional instances among those 17 cases, the
yields realized with 1b were about the same as the
maximum yield found in the literature, and in only one
2.2. Homogeneously catalyzed Strecker reactions
For the Strecker reaction, we initially examined 1c and 1d as
promoters (20 mol%) for the three-component model
reaction employing benzaldehyde, aniline, and TMSCN in
acetonitrile at room temperature for 12 h. Although the
Table 2. Room temperature thia-Michael reactions promoted by 1ba
Entry
Donor
Acceptor
Time
(h)
Product
w/o cat.
(%)b
Yield w/1b
(%)b
Lit. Yield
(%)c
1
2
3
40
40
40
40
95
98
98
94
66–725a,c
30
20
925a
925a
4
65–924b,5a
5
6
7
n-BuSH
n-BuSH
n-BuSH
48
48
48
90
98
99
705a
885a
905a
NR
8
n-BuSH
48
93
734b
a Conditions: thiol (2.0 mmol), acceptor (2.5 mmol), 1b (10 mol%) and CH3CN (3 mL).
b Isolated yields.
c Literature yields.

444
Table 3. Room temperature preparation of a-aminonitriles using 1b as a promotera
Entry Aldehyde Amine Product
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
Time
(h)
% Yield
w/1bb
Lit. Yield
(%)c
1
12
15
94
91
75–92d, 15b16a,d
2
9715b
3
4
12
8
90
93
73–96d, 15a,b
e
–
e
–
5
12
90
f, 15a,c
6
7
15
15
92
90
–
e
–
8
9
8
98
98
82d, 15b
15
78d, 16c
10
15
92
83d, 17f
11
12
25
25
82
80
7515a
e
–
13
14
12
15
88
90
7415a
75–91d, 15a,16a

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
445
Table 3 (continued)
Entry
Aldehyde
Amine
Product
Time
(h)
% Yield
w/1bb
Lit. Yield
(%)c
15
15
25
88
85
9715b
e
–
16
17
18
15
20
93
95
9415c
9715c
19
15
82
66d, 15b
a Conditions: aldehyde or ketone (1.0 mmol), amine (1.0 mmol), TMSCN (1.2 mmol), 1b (20 mol%) and CH3CN (3 mL).
b Isolated yields.
c Literature yields.
d Three-component coupling reaction.
e New compound.
f
The yield was reported as quantitative.
yields were disappointing (75 and 60%, respectively) the
same reaction with 20 mol% of 1b provided a 94% yield of
the desired product. The use of dichloromethane as a solvent
in this reaction gave a poor yield (40%) in a very slow (12 h)
reaction probably owing to incomplete solution of 1b.
detectable product after 25 h, the reaction of cyclohexanone
with benzylamine and TMSCN under the same conditions
gave an 82% product yield after 15 h (entry 19).
From Table 3 it is seen that, of the literature yields reported
for three-component reactions (entries 1, 3, 8–10, 14, and
19), our protocol delivers a substantially higher yield in four
of the seven cases, and yields that are near or at the upper
end of the literature range in the other three cases. In the
remaining entries in which literature yields were reported
for perhaps less risky two-step syntheses (entries 2, 6, 8, 11,
13, and 15–18) our one-pot methodology produced higher
yields in three of the nine cases, very comparable yields in
two cases and lower yields in four instances.
Benzaldehyde (1.0 mmol) reacted with a variety of amines
(1.0 mmol) in the presence of 20 mol% of 1b and TMSCN
(1.2 mmol) in CH3CN to give excellent product yields
(Table 3, entries 1, 3, 4, 6–10). Secondary amines (Table 3,
entries 8 and 9) reacted relatively quickly to give 98%
product yields and n-hexylamine (entry 10) also gave a high
yield of product of 83%. Piperonal reacted with amines,
giving the corresponding a-aminonitrile in excellent yield
(entries 2 and 5). Aliphatic aldehydes also reacted well with
aniline, affording good product yields (entries 11 and 12).
Aniline reacted with substituted aromatic aldehydes,
affording 85–90% product yields (entries 13–16) and the
heterocycles in entries 17 and 18 gave a 93 and 95% yield of
desired product, respectively. Reactions of the type reported
here are very sluggish without promoter 1b, as was shown
for the reaction in entry 1, in which case, 3 days were
necessary to achieve a 90% product yield.
For the four-component one-pot synthesis of a-amido-
nitriles, we employed 20 mol% of 1b, benzaldehyde
(1.0 mmol), benzylamine (1.0 mmol), trimethylsilyl
cyanide (1.2 mmol), and acetic anhydride (1.0 mmol).
After 20 h at room temperature, a 40% yield (based on
benzaldehyde) of the coupling product was realized.
Increasing the quantity of acetic anhydride to 1.5 mmol
improved the product yield to only 60%. After further
attempts to increase the yield by changing relative
concentrations of the reactants, we found that a mixture of
30 mol% of 1b, benzaldehyde (1.0 mmol), benzylamine
(1.0 mmol), trimethylsilyl cyanide (1.2 mmol), and acetic
anhydride (2.0 mmol) stirred at room temperature for 25 h
gave a good yield (82%) of product (entry 1 in Table 4). We
also observed that after addition of the TMSCN, it was
advantageous to quickly add the acetic anhydride in order to
To our knowledge, only two reports of Strecker-type
reactions with ketones appear in the literature.17b,29 In one
case InCl3 was the catalyst for cyclohexanones17b and in the
second, elevated pressure in the absence of a catalyst was
employed for aliphatic and aromatic ketones.29 Although
the reaction of acetophenone with aniline and TMSCN in
the presence of 20 mol% of 1b at room temperature gave no

446
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
Table 4. Room temperature preparation of a-amidonitriles using 1b as a promoter and acetic anhydride as the acetylating reagenta
Entry
1
Aldehyde
Amine
Product
Time (h)
25
Yield (%)b
82
2
25
84
3
4
25
30
85
86
5
6
35
25
60
70
7
8
9
35
35
25
73
50
74
10
11
25
30
76
65
12
25
80
13
14
25
30
75
72
a Conditions: aldehyde (1.0 mmol), amine (1.0 mmol), TMSCN (1.2 mmol), (CH3CO)2O (2.0 mmol), 1b (30 mol%) and CH3CN (3 mL).
b Isolated yields. None of the products in Table 4 have been described in the literature.

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
447
avoid decreased yields. Substituting acetyl chloride for
acetic anhydride gave no detectable amount of product.
Using 30 mol% of the commercially available catalysts
InCl3 or Bi(NO3)3 gave only acylated amine.
variety of aryl aldehydes with different amines, 50–80%
yields of the corresponding coupling products were realized
(Table 4, entries 6–12). The relatively low yields obtained in
the case of propargylamine may be due to side reactions
associated with its reactivity with the aldehyde and/or with
acetic anhydride. The heterocycles in entries 13 and 14 gave
in each case reasonable product yields. Although none of the
products in Table 4 were found in the literature, the yields
for the 14 products listed in this table are good (80–86%) in
Stirring a mixture of benzaldehyde, 1b, an amine, TMSCN
and acetic anhydride as specified in Table 4 gave product
yields ranging from 60–86% yields as shown in entries 1–5
of this table. Extending this chemistry to reactions of a
Table 5. Room temperature aza-Michael reaction in the presence of 3 as a promoter
Entrya
Donor
Acceptor
Product
Yield (%)
80
1
2b
70
92
3b
4b
92
99
5
6
7
99
82
8
89
9
99
84
10b
11
12
95
99
a Conditions: amine (1.5 mmol), acceptor (1.9 mmol), 3 (10 mol%) and CH3CN (2 mL). Reactions were run for 24 h at room temperature.
b Reaction temperature was 60 8C.

448
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
five instances, moderate (60–75%) in eight cases and
modest in only one (50%).
or electron rich anilines (Table 5, entries 2–4). Aliphatic
amines also react with various Michael acceptors (Table 5,
entries 5–9) providing the desired products in very good to
excellent yields. 1-Aminonaphthalene, on the other hand,
required a reaction temperature of 60 8C to afford a product
yield (Table 5, entry 10) comparable to other products in
this table. The same reaction at room temperature produced
only a 30% yield. Benzylic amines (Table 5 entries 11 and
12) also react cleanly to give the desired products in
excellent yields.
A drawback of our four-component methodology is that no
coupling product stemming from aniline as a reagent was
detected. This result may be attributed to steric hindrance
provided by the phenyl group. Thus, our protocol is
effective, however, with benzyl amine (entries 1, 9, 11,
and 12 in Table 4).
Upon extending our protocol to thiols, excellent yields of
products were found in all cases (Table 6). It should also be
noted that no electrophilic substitution was observed when
an aromatic thiol was employed as the Michael donor
(Table 6, entries 1–4).
Workup is simplified in many cases because column
chromatography can be avoided. In cases where there are
no aromatic groups on the amine, the polymeric catalyst is
filtered from the reaction mixture, and washed well to
remove any remaining traces of products and starting
materials. After removal of the volatile compounds and
solvent on a vacuum line, the desired products are NMR
pure.
Scheme 2. Synthesis of 3.
2.3. Heterogeneously catalyzed Michael reactions
We reported the synthesis of the triflate salt of a polymer-
bound azaphosphatrane several years ago21 and we
synthesized 3 by an analogous route (Scheme 2). Our
conditions for the nitrate-catalyzed Michael additions are
mild (Tables 5 and 6). It is seen in Table 5 that electron
neutral (entries 1 and 2) and electron rich anilines (entries 3
and 4) react readily with methyl vinyl ketone, but higher
temperatures are sometimes needed for sterically hindered
2.4. Heterogeneously catalyzed Strecker reactions
Results of the Strecker-type reactions promoted by 3 are
Table 6. Room temperature thia-Michael reactions promoted by 3
Entrya
Donor
Acceptor
Product
Yield (%)
1
99
2
3
99
99
4
5
99
99
6
7
99
99
8
99
a Conditions: thiol (1.5 mmol), acceptor (1.9 mmol), 3 (10 mol%) and CH3CN (2 mL). Reactions were run for 48 h at room temperature.

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
449
Table 7. Room temperature preparation of a-aminonitriles using 3 as a promoter
Entrya
Aldehyde Amine
Product
Time
12
Yield (%)
99
1
2
3
15
12
99
99
4
5
8
99
99
12
6
7
15
15
99
99
8
9
8
99
99
15
10
11
15
25
99
90
12
13
25
12
90
99
14
15
15
15
99
97

450
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
Table 7 (continued)
Entrya
Aldehyde
Amine
Product
Time
25
Yield (%)
16
89
17
18
15
20
95
99
a Conditions: aldehyde or ketone (1.5 mmol), amine (1.5 mmol), TMSCN (1.8 mmol), 3 (20 mol%) and CH3CN (2 mL).
summarized in Table 7. The isolated yields are seen to be
excellent in all cases, and both aromatic and aliphatic
amines react well. The same cannot be said for aromatic and
aliphatic aldehydes. While aromatic aldehydes were willing
participants in the reaction, the reactions with aliphatic
aldehydes proved sluggish (Table 7 entries 11 and 12).
Moreover, the yields in these reactions, while impressive,
are slightly lower than those achieved with the various
benzaldehydes tested.
recycled only 11 times. The 12th reaction required twice as
much time to achieve a similar yield as the previous 11 uses
of the catalyst. The 13th cycle failed to give any product
after 24 h. The catalyst can be reactivated, however, upon
treatment with 3 M aqueous sodium nitrate. The reactivated
catalyst behaved identically to a freshly prepared sample.
When we tested the re-usability of polymer-bound promoter
3 a second time in the four-component coupling reaction of
benzaldehyde, benzylamine, TMSCN, and acetic anhydride
the isolated product yield dropped from 90 to 73%. We
conjectured that the water and acetate ion side products in
the reaction displaced nitrate ion from 3, thereby decreasing
its effectiveness in the reaction. These problems were easily
overcome by a simple washing of the polymer with aqueous
sodium nitrate. The regenerated polymer then behaved
identically to a fresh sample in the reaction.
Because we observed excellent results for the synthesis of
Reissert compounds homogeneously promoted by 1b
(Table 4) we decided to extend that work with the utilization
of the heterogeneous catalyst 3, the results of which are
contained in Table 8. Benzaldehyde willingly participated
in this reaction, giving products with various amines in 80–
90% yield (Table 8, entries 1–5). Other functionalized
benzaldehdyes gave products in varying yields (Table 8,
entries 6–12). It is not clear why low product yields were
obtained in a few cases (Table 8, entries 8 and 12).
Heterocycles gave the desired coupling products in modest
to good yield (Table 8, entries 13–14).
2.6. Mechanistic considerations
Representative reactions chosen from Tables 1 and 2, when
carried out under the same conditions in the absence of
catalyst 1b, either produced no detectable amount of
product or gave substantially lower product yields. To
compare the efficacy of 1b with Bi(NO3)3, we also carried
out the reaction in entry 1 of Table 1 with the latter salt,
albeit with only 3.3 mol% in order to maintain 10 mol% of
nitrate ion concentration in the reaction mixture. The
product yield in that reaction (80%) was close to the 78%
yield realized with 1b. This result suggests (a) that the
bismuth ion is not active as a catalyst whereas nitrate is,
(b) that the bismuth ion is as active as naked nitrate (and that
the nitrate is completely inactivated owing to anion–cation
interactions), or (c) that the situation is somewhere between
these two extremes (a more likely scenario in our view).
2.5. Catalyst re-usability
The re-usability of polymer-bound nitrate salt 3 was
evaluated in the Michael addition of aniline to methyl
vinyl ketone as a model system. We found that when
precautions were taken to avoid moisture, polymer 3 can be
recycled up to 20 times without loss of activity. However,
when water (1 equiv based on the amine) was added, the
amount of desired product isolated decreased sharply after
four cycles. It is likely that hydroxide ion formed in the
reaction of the amine with the water allows nitrate ion to be
exchanged from the cationic polymer resin into the reaction
solution. The catalytic activity of 3 is easily recovered,
however, by washing the nitrate-depleted resin with
aqueous sodium nitrate.
We have also performed a competition experiment between
aniline and benzylamine, which showed that the nucleo-
philicity of the amine plays an important role in this
reaction. Here, we observed that methyl acrylate reacted
selectively with benzylamine to give the desired product in
nearly quantitative yield while aniline was recovered
unreacted.
Furthermore, we found that resin bound azaphosphatrane
nitrate catalyst 3 can be recycled 20 times with no loss of
catalytic activity in the three component coupling of
purified benzaldehyde, aniline, and trimethylsilylcyanide.
However, when the benzaldehyde and aniline were taken
from previously opened bottles exposed to air, the resin
To investigate whether or not the P– and N– bonds in 1b

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
451
Table 8. Room temperature preparation of a-amidonitriles using 3 as a promoter and acetic anhydride as the acetylating reagent
Entrya
Aldehyde
Amine
Product
Time (h)
Yield (%)
1
25
90
2
25
90
3
4
5
25
30
35
89
80
80
6
7
8
9
25
35
35
25
60
71
29
90
10
11
25
30
90
80

452
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
Table 8 (continued)
Entrya
Aldehyde
Amine
Product
Time (h)
Yield (%)
12
25
29
13
14
25
30
47
80
a Conditions: aldehyde (1.5 mmol), amine (1.5 mmol), TMSCN (1.8 mmol), (CH3CO)2O (3.0 mmol), 3 (30 mol%) and CH3CN (2 mL).
play a role in the reaction, we utilized nitrate salt 4.30 This
salt behaved identically when used in place of 1b in the
Michael addition of aniline to methyl vinyl ketone. Since 4
contains no groups that might be deprotonated to produce
nitric acid in situ, we can rule out dissociation of 1b in
solution to produce an active catalytic species.
14 times faster in the presence of 1b than in its absence. The
same monitoring experiment was carried out for the reaction
of TMSCN (0.100 mmol, 13.3 mL) with H2O (0.100 mmol,
1.80 mL) in CD3CN (0.7 mL) in the absence and presence of
1b (20 mol%). Here, we observed that the peak position of
TMSCN disappeared too quickly compared with product
resonances, thus precluding a conclusion. However, when a
solution of N-benzylidene aniline (1 mmol), TMSCN
(1.2 mmol) and 20 mol% of 1b in 3 mL of acetonitrile
was stirred at room temperature for 12 h, a 94% yield of the
expected product was obtained. When the same reaction
was carried out in the absence of promoter, a 50% yield of
the product was obtained. From these experiments it is clear
that 1b promoted both imine formation and cyanide
addition.
The results taken in toto prompt us to propose the
mechanism in Scheme 3. Initially, the amine adds to the
electron deficient carbon atom of the Michael acceptor and
nitrate ion in this case acts as a ‘proton shuttle’, utilizing
hydrogen bonding to facilitate transfer of the proton from
nitrogen to oxygen.
Other nitrate ion sources (20 mol%) were also tested in a
model reaction of benzaldehyde, aniline, and TMSCN. Both
sodium nitrate and 1,1,3,3-tetramethylguanidinium nitrate
were ineffective, a result that can be attributed to the
observed incomplete solution of these salts. When 15-
crown-5 was added to the sodium nitrate, an 89% yield of
the desired product was isolated, suggesting that effective
inhibition of anion–cation interactions is important. The
somewhat higher yield (94% in entry 1 of Table 3) indicates
that this inhibition is somewhat stronger for 1b. CAN
proved to be completely ineffective, giving a large number
In order to gain an idea regarding how the three-component
reactions described here are accelerated by 1b, a mixture of
benzaldehyde (0.1 mmol) and aniline (0.1 mmol) in CD3CN
(0.7 mL) was monitored by H NMR spectroscopy for a
period of 12 h at room temperature with and without
20 mol% of 1b present. It was found that imine formation is
1
Scheme 3. Proposed mechanism of nitrate-catalyzed aza and thia-Michael reactions.

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
453
Scheme 4. Proposed mechanism of four-component coupling reactions catalyzed by 1b.
of spots on TLC. Tetrabutylammonium nitrate was only
mildly efficacious, permitting isolation of a 49% yield of
product.
for 30 min. A solution of HNO3 [concd HNO3 (69%)
12 mmol] in acetonitrile (5 mL) was slowly added to the
reaction mixture and the byproduct Me2NH was allowed to
escape while stirring at room temperature for 15 h. The
solvent was distilled under vacuum and the residue was
washed with ether and dried under vacuum to afford the
solid product.
On the basis of the foregoing observations, we suggest that
the nitrate ion acts as a proton shuttle in these transform-
ations (Scheme 4) and that the nitrate ion is rendered quite
‘naked’ by delocalization of the positive charge among the
four nitrogens and the phosphorus atom in the cation of 1b.
It may be noted that this cation is relatively modest in size
compared with a [Na(15-crown-5)]C or a [NBu4]C species,
for example.
4.3. Preparation of 1e and 1g
To a stirred solution of P(MeNCH2CH2)3N or P(i-BuNCH2-
CH2)3N (1 mmol) in acetonitrile (5 mL) was added HNO3
[concd HNO3 (69%) 1.5 mmol, 0.1 mL] drop wise very
slowly. After stirring the solution at room temperature for
6 h, the solvent was removed under vacuum and the residue
was washed with hexane and then ether. The residue was
dried under vacuum to afford the solid product in 95% (1e)
and 94% (1g) yields, respectively.
3. Conclusion
We have developed a novel and efficient azaphosphatrane
nitrate catalyst that operates at room temperature in nearly
all cases for not only aza and thia-Michael reactions, but
also for Strecker and four-component coupling reactions.
When bound to a solid support, this catalyst shows excellent
catalytic activity at room temperature in the above
reactions, and it is also recyclable. Investigations are
currently underway of the catalytic activity of other anions
that behave as strong bases in non-aqueous solvents31 and
which are rendered ‘naked’ by cations of the phosphatrane
type.
4.4. General procedure for aza and thia-Michael
reactions promoted by 1b
To a stirred acetonitrile (3 mL) solution of 1b (10 mol%)
was added an amine or thiol (2 mmol) followed by stirring
at room temperature under argon. An acceptor (2.5 mmol)
was added to the reaction mixture followed by stirring at
room temperature for 20–50 h (see Tables 1 and 2). The
solvent was evaporated to dryness and the product was
purified by chromatography over silica gel using 5% ether-
in-hexane for Table 2, entries 1 and 3; 10% ether-in-hexane
for Table 2, entries 2 and 4–8; 20% ether-in-hexane for
Table 1, entries 1, 2, 5, and; 50% ether-in-hexane for
Table 1, entries 3 and 4; and ether for Table 1, entries 6–10,
12, and 13 as eluent. 1H and/or 13C NMR data are reported
for known compounds in the literature references and our
corresponding data compared well.
4. Experimental
4.1. General considerations
All reactions were conducted under argon. All solvents were
collected from a Grubbs-type two column solvent purifi-
˚
cation system and kept under 4 A molecular sieves. NMR
spectrometers employed were a Varian VXR-300 for 1H and
13C spectra and a Varian VXR-400 for 31P spectra.
Standards for the NMR spectra were TMS (1H, internal),
85% H3PO4 (31P, external). High-resolution mass spectra
were recorded on a KRATOS MS-50 spectrometer. Silica
gel (Baker, 40–140 mesh) was used for column chroma-
tography. All chemicals were purchased from Aldrich or
Fisher.
4.5. General procedure for the synthesis of a-amino-
nitriles promoted by 1b
A mixture of 1a (20 mol%), aldehyde (1.0 mmol), amine
(1.0 mmol), and trimethylsilyl cyanide (1.2 mmol) was
stirred in acetonitrile (3 mL) under argon at room
temperature for 8–25 h. The solvent was evaporated to
dryness and the product was purified by silica gel column
chromatography using 5% ether-in-hexane for Table 3
entries 1, 2, 6, 7, 9–12, 14, and 19; 10% ether-in-hexane for
Table 2, entries 3, 4, 13, and 15–18; 20% ether-in-hexane
for Table 2, entry 5; and 25% ether-in-hexane for Table 2,
4.2. Preparation of 1b
HMPT (10 mmol) was added to an ice-cold acetonitrile
(25 mL) solution of tris(2-aminoethyl)amine (10 mmol)
under argon and the mixture was stirred at room temperature

454
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
entry 8 as eluents. 1H and/or 13C NMR data are reported for
known compounds in the literature references and our
corresponding data compared well.
was cannulated in. The experiment was then repeated. The
product was purified as described in the preceding
paragraph.
4.6. General procedure for the synthesis of a-amido-
nitriles promoted by 1b
4.9. General procedure for four component coupling
promoted by 3
A mixture of 1a (30 mol%), aldehyde (1.0 mmol), amine
(1.0 mmol), trimethylsilyl cyanide (1.2 mmol), and acetic
anhydride (2.0 mmol) in acetonitrile (3 mL) was stirred
under argon at room temperature for 25–35 h. The reaction
mixture was evaporated to dryness and the product was
purified by column chromatography over silica gel using
50% ether-in-hexane for Table 2 entries 1–5, and 7–14 and
ether for Table 3, entry 6 as eluent.
The catalyst (30 mol% based on the aldehyde and amine)
was weighed into a 10 mL round bottomed flask. The
aldehyde (1.5 mmol), amine (1.5 mmol), TMSCN
(1.8 mmol), and acetic anhydride (3.0 mmol) were pre-
mixed in acetonitrile (2 mL) and cannulated into the flask
with the catalyst. The reaction was then stirred magnetically
at room temperature until the conditions in Table 8 had been
met. The catalyst was then filtered off and washed with
w10 mL of acetonitrile. The product was then purified by a
short path silica gel column using solvent mixtures given in
Section 4.6.
4.7. General procedure for Michael addition promoted
by 3
The Michael donor (1.5 mmol) the acceptor (2.25 mmol)
and acetonitrile (2 mL) were combined and then the mixture
was added to 3 whose catalyst capacity was calculated from
the phosphorus elemental analysis (1.98 mmol/g). The
weight of 3 used was 106 mg (10 mol% based on the
Michael donor). The reaction mixture was stirred and after
the conditions in the Tables 5 and 6 had been met, the
polymer was filtered off and washed with w10 mL of
acetonitrile. The solvent and volatiles were then removed
from the acetonitrile solution under reduced pressure
(w40 mmHg). Products were then subjected to column
chromatography on silica gel where necessary to give the
pure compound.
For the re-use of 3, the procedure in the previous paragraph
was followed. After the reaction time indicated in Table 7
for a benzaldehyde/aniline/TMSCN/acetic anhydride
reaction mixture, stirring was stopped and the polymer
was allowed to settle. The supernatant was then carefully
cannulated off, and a new mixture of starting materials was
cannulated in. The experiment was then repeated. The
product was purified as described in the previous paragraph.
4.10. Reactivation of 3
Samples of used 3 from previous experiments (approxi-
mately 500 mg) were combined into a 100 mL flask
followed by the addition of 30 mL of a 3 M aqueous
sodium nitrate solution. The suspension was stirred for 2 h
at room temperature and filtered. The polymer was washed
with water, 3 M sodium nitrate, water, methanol, THF, and
ether (w20 mL each). The polymer was then dried under
reduced pressure at room temperature for 24 h.
For the re-use of 3, the procedure in the previous paragraph
was followed for an aniline/MVK/3 mixture, which was
stirred for 24 h at room temperature. Stirring was then
stopped, the solution was allowed to settle and then the
supernatant was decanted by cannula and the polymer was
washed with w10 mL of acetonitrile. Another aniline/MVK
mixture was then cannulated into the polymer catalyst and
the procedure repeated.
Acknowledgements
4.8. General procedure for the Strecker-type reaction
promoted by 3
We thank the National Science Foundation for a grant that
supported this research, Aldrich for generous gifts of
research samples, and Professor George Kraus for helpful
discussions.
The catalyst (20 mol% based on the aldehyde and amine)
was weighed into a 10 mL round bottomed flask. The
aldehyde (1.5 mmol), amine (1.5 mmol), and TMSCN
(1.8 mmol) were premixed in acetonitrile (2 mL) and
cannulated into the flask containing the catalyst. The
reaction was then stirred magnetically at room temperature
until the conditions in Table 7 had been met. The catalyst
was then filtered off and washed with w10 mL of
acetonitrile. The product was purified by a short path silica
gel column using mixtures of 5–25% ether in hexane as the
eluent. Exact solvent mixtures are given in Section 4.5.
Supplementary data
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/j.tet.2005.
09.117.
For the re-use of 3, the procedure for the experiment in the
previous paragraph was followed. After the reaction time
indicated in Table 7 for a benzaldehyde/aniline/TMSCN
reaction mixture, stirring was stopped and the polymer was
allowed to settle. The supernatant was then carefully
cannulated off, and a new mixture of starting materials
References and notes
1. (a) Traxler, P.; Trinks, U.; Buchdunger, E.; Mett, H.; Meyer,
T.; Muller, M.; Regenass, U.; Rosel, J.; Lydon, N. J. Med.

B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
455
Chem. 1995, 38, 2441. (b) Perlmutter, P. Conjugate Addition
Reactions in Organic Synthesis; Pergamon: Oxford, UK, 1992.
(c) Trost, B. M., Ed.; Comprehensive Organic Synthesis;
Pergamon: Oxford, UK, 1991; Vol. 4.
Muller, S. F.; Raabe, G. Synlett 1999, 741. (c) Li, A.-H.; Moro,
S.; Forsyth, N.; Melman, N.; Ji, X.-D.; Jacobson, K. A. J. Med.
Chem. 1999, 42, 706. (d) Enders, D.; Wiedemann, J. Synthesis
1996, 1443. (e) Kobayashi, S.; Ishitani, H. Chem. Commun.
1995, 1379. (f) Wasserman, H. H.; Rotello, V. M.; Krause,
G. B. Tetrahedron Lett. 1992, 33, 5419. (g) Reitz, A.;
Verlander, M.; Goodman, M. Tetrahedron Lett. 1982, 23, 751.
11. (a) Kotrusz, P.; Toma, S.; Schmalz, H. G.; Adler, A. Eur.
J. Org. Chem. 2004, 1577. (b) Halland, N.; Aburel, P. S.;
Jorgensen, K. A. Angew. Chem., Int. Ed. 2004, 43, 1272. (c)
Halland, N.; Hansen, T.; Jorgensen, K. A. Angew. Chem., Int.
Ed. 2003, 42, 4955. (d) Halland, N.; Hazell, R. G.; Jorgensen,
K. A. J. Org. Chem. 2002, 67, 8331.
2. (a) Wroblewski, A. E.; Bansal, V.; Kisanga, P.; Verkade, J. G.
Tetrahedron 2002, 59, 561. (b) Sundararajan, G.; Prabagaran,
N. Org. Lett. 2001, 3, 389. (c) Manickam, G.; Sundararajan, G.
Tetrahedron 1999, 55, 2721. (d) Ranu, B. C.; Bhar, S.
Tetrahedron 1992, 48, 1327.
3. (a) Enders, D.; Haertuig, A.; Raabe, G.; Runsink, J. Eur.
J. Org. Chem. 1998, 1793. (b) Enders, D.; Haertuig, A.; Raabe,
G.; Runsink, J. Eur. J. Org. Chem. 1998, 1771. (c) Enders, D.;
Haertuig, A.; Raabe, G.; Runsink, J. Angew. Chem., Int. Ed.
1996, 35, 2388. (d) Hosokawa, T.; Shinohara, T.; Ooka, Y.;
Murahashi, S.-I. Chem. Lett. 2001, 1989. (e) Gutman, A. L.;
Meyer, E.; Boltanski, A. Synth. Commun. 1988, 18, 1311. (f)
Bloomfield, J. J. J. Org. Chem. 1962, 27, 2742.
12. Strecker, A. Ann. Chem. Pharm. 1850, 75, 27.
13. (a) March, J. Advanced Organic Chemistry, 4th ed.; Wiley:
New York, 1999; p 965. (b) Shafran, Y. M.; Bakulev, V. A.;
Mokrushin, V. S. Russ. Chem. Rev. 1989, 58, 148.
4. (a) Sani, M.; Bruche, L.; Chiva, G.; Fustero, S.; Piera, J.;
Volonterio, A.; Zanda, M. Angew. Chem., Int. Ed. 2003, 42,
2060. (b) Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68,
2109. (c) Chen, J. J.; Lu, C. V.; Brockman, R. N. Tetrahedron
Lett. 2003, 44, 3459. (d) Kobayashi, S.; Kakumoto, K.;
Sugiura, M. Org. Lett. 2002, 4, 1319. (e) Bartoli, G.; Basco,
M.; Marcantoni, E.; Petrini, M.; Sambri, L.; Torregiani, E.
J. Org. Chem. 2001, 66, 9052. (f) Miller, K. J.; Kitagawa,
T. T.; Abu-Omar, M. M. Organometallics 2001, 20, 4403. (g)
Shaikh, N. S.; Deshpande, V. H.; Bedekar, A. V. Tetrahedron
2001, 57, 9045. (h) Pinto, A. C.; Abdala, R. V.; Costa, P. R. R.
Tetrahedron: Asymmetry 2000, 11, 4239. (i) Enders, D.;
Muller, S. F.; Raabe, G. Angew. Chem., Int. Ed. 1999, 38, 195.
(j) Loh, T.-P.; Wei, L.-L. Synlett 1998, 975. (k) Barco, A.;
Benetti, S.; Risi, C. D.; Pollini, G. P.; Romagnoli, R.; Zanirato,
V. Tetrahedron Lett. 1994, 35, 9293. (l) Cabral, J.; Laszlo, P.;
Mahe, L.; Montaufier, M.-T.; Randriamahefa, S. L.
Tetrahedron Lett. 1989, 30, 3969. (m) Combret, J.-C.; Klein,
J.-L.; Mouslouhouddine, M. Tetrahedron Lett. 1984, 25, 3449.
(n) Horii, Z.; Ikeda, M.; Tamura, Y.; Watanabe, T., Yakugaku
Zasshi 1962, 82, 706; Chem. Abstr. 1963, 58, 5629.
14. (a) Matier, W. L.; Owens, D. A.; Comer, W. T.; Ditchman, D.;
Ferguson, H. C.; Seidehamel, R. J.; Young, J. R. J. Med. Chem.
1973, 16, 901. (b) Weinstock, L. M.; Davis, P.; Handelsman,
B.; Tull, R. J. Org. Chem. 1967, 32, 2823.
15. (a) Sigman, M. S.; Vachal, P.; Jacobsen, E. N. Angew. Chem.,
Int. Ed. 2000, 39, 1279. (b) Heydari, A.; Fatemi, P.; Alizadeh,
A. A. Tetrahedron Lett. 1998, 39, 3049. (c) Kobayashi, S.;
Busujima, T.; Nagayama, S. Chem. Commun. 1998, 981.
16. (a) Cooney, J. V. J. Heterocycl. Chem. 1983, 20, 823. (b) Popp,
F. D. Heterocycles 1973, 1, 165. (c) Popp, F. D. Adv.
Heterocycl. Chem. 1968, 9, 1. (d) McEwen, W. E.; Cobb, R. L.
Chem. Rev. 1955, 55, 511.
17. (a) Vachal, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124,
10012. (b) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron
2002, 58, 2529. (c) Ishitani, H.; Komiyama, S.; Hasegawa, Y.;
Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 762. (d) Ishitani,
H.; Komiyama, S.; Kobayashi, S. Angew. Chem., Int. Ed. 1998,
37, 3186. (e) Kobayashi, S.; Ishitani, H.; Ueno, M. Synlett
1997, 115. (f) Leblanc, J. P.; Gibson, H. W. J. Org. Chem.
1994, 59, 1072. (g) McEwen, W. E.; Grossi, A. V.;
MacDonald, R. U.; Stamegna, A. P. J. Org. Chem. 1980, 45,
1301. (h) Naim, S. S.; Khan, N. H.; Siddiqui, A. A. Indian
J. Chem. Sect B 1980, 622. (i) Neelakantan, L.; Hartung, W. H.
J. Org. Chem. 1959, 24, 1943.
5. (a) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2003, 59,
2417. (b) Yadav, J. S.; Reddy, B. V. S.; Baishya, G. J. Org.
Chem. 2003, 68, 7098. (c) Wabnitz, T. C.; Spencer, J. B. Org.
Lett. 2003, 5, 2141. (d) McDaid, P.; Chen, Y.; Deng, A.
Angew. Chem., Int. Ed. 2002, 41, 338. (e) Emori, E.; Arai, T.;
Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 4043.
6. (a) Bartoli, G.; Cimarelli, C.; Marcantoni, E.; Palmieri, G.;
Petrini, M. J. Org. Chem. 1994, 59, 5328. (b) Elango, S.; Yan,
T.-H. J. Org. Chem. 2002, 67, 6954. (c) Elango, S.; Yan, T.-H.
Tetrahedron 2002, 58, 7335 and references cited therein.
7. (a) Elkaim, L.; Grimaud, L.; Jana, N. K.; Mettetal, F.; Tirla, C.
Tetrahedron Lett. 2002, 43, 8925. (b) Gross, S.; Reissig, H.-U.
Synlett 2002, 2027. (c) Dumez, E.; Faure, R.; Dulcere, J. P.
Eur. J. Org. Chem. 2001, 2577. (d) Dulcere, J. P.; Dumez, E.
Chem. Commun. 1997, 971. (e) Dumez, E.; Rodriguez, J.;
Dulcere, J. P. Chem. Commun. 1997, 1831.
18. (a) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.; Srinivas, M.
Tetrahedron 2004, 60, 1767. (b) Fossey, J. S.; Richards, C. J.
Tetrahedron Lett. 2003, 44, 8773. (c) Mansawat, W.;
Bhanthumnavin, W.; Vilaivan, T. Tetrahedron Lett. 2003,
44, 3805. (d) Yadav, J. S.; Reddy, B. V. S.; Eeshwaraiah, B.;
Srinivas, M.; Vishumurthy, P. New J. Chem. 2003, 27, 462. (e)
Sun, P.; Qian, C.; Wang, L.; Chen, R. Synth. Commun. 2002,
32, 2973.
19. (a) Leblanc, J. P.; Gibson, H. W. Tetrahedron Lett. 1992, 33,
6295. (b) Chakraborty, T. K.; Reddy, G. V.; Hussain, K. A.
Tetrahedron Lett. 1991, 32, 7597.
20. McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. Rev. 2002,
102, 3275 and references cited therein.
8. Boger, D. L.; Aquila, B. M.; Tse, W. C.; Searcey, M.
Tetrahedron Lett. 2000, 41, 9493.
21. Liu, X.; Verkade, J. G. J. Org. Chem. 1999, 64, 4840.
22. Ilankumaran, P.; Verkade, J. G. J. Org. Chem. 1999, 64, 9063.
23. Wabnitz, T. C.; Yu, J.; Spencer, J. B. Synlett 2003, 1070.
24. (a) Athawale, V.; Manjrekar, N. Tetrahedron Lett. 2001, 42,
4541. (b) Hodge, P.; Khoshdel, E.; Waterhouse, J.; Frechet,
J. M. J. Chem. Soc., Perkin Trans. 1 1985, 2327. (c) Hodge, P.;
Khoshdel, E.; Waterhouse, J. J. Chem. Soc., Perkin Trans. 1
1983, 2205.
9. (a) Senanayake, C. H.; Fang, K.; Glover, P.; Bakale, R. P.;
Vandenbassche, C. P.; Wald, S. A. Tetrahedron Lett. 1999, 40,
819. (b) Genov, M.; Dimitrov, V.; Ivanova, V. Tetrahedron:
Asymmetry 1997, 8, 3703. (c) Hayashi, Y.; Rode, J. J.; Corey,
E. J. J. Am. Chem. Soc. 1996, 118, 5502. (d) Eliel, E. L.; He,
X.-C. J. Org. Chem. 1990, 55, 2114.
10. (a) Enders, D.; Wallert, S. Synlett 2002, 304. (b) Enders, D.;

456
B. M. Fetterly et al. / Tetrahedron 62 (2006) 440–456
25. Miller, J. M.; Cater, S. R.; So, K.; Clark, J. H. Can. J. Chem.
1979, 57, 2629.
1991, 605, 163. (c) Lensink, C.; Xi, S. K.; Verkade, J. G. J. Am.
Chem. Soc. 1989, 111, 3478. (d) Xi, S. K.; Verkade, J. G. Z.
Anorg. Allg. Chem. 1989, 578, 75.
26. Nogami, H.; Matsunaga, S.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2001, 42, 279.
29. Matsumoto, K.; Kim, J. C.; Hayashi, N.; Jenner, G.
Tetrahedron Lett. 2002, 43, 9167.
27. Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120,
4901.
30. Kingston, J. V.; Verkade, J. G., manuscript in preparation.
31. Kolthoff, S.; Bruckenstein, S.; Chantooni, M. K. J. Am. Chem.
Soc. 1961, 83, 3927.
28. (a) Kisanga, P. B.; Verkade, J. G. Tetrahedron 2001, 57, 467.
(b) Laramay, M. A.; Verkade, J. G. Z. Anorg. Allg. Chem.