1,3,5-triaza-7-phosphaadamantane (PTA): A practical and versatile nucleophilic phosphine organocatalyst

Article abstract of DOI:10.1002/adsc.200700071

In this paper, the air-stable and readily available 1,3,5-triaza-7- phosphaadmantane (PTA) is reported as a practical and versatile nucleophilic phosphine organocatalyst. Under the mediation of 15-30 mol% of PTA, various electrophiles like aldehydes and i

Full text of DOI:10.1002/adsc.200700071

FULL PAPERS
DOI: 10.1002/adsc.200700071
1,3,5-Triaza-7-phosphaadamantane (PTA): A Practical and
Versatile Nucleophilic Phosphine Organocatalyst
Xiaofang Tang,a Bo Zhang,a Zhengrong He,a Ruili Gao,a and Zhengjie Hea,*
a
State Key Laboratory of Elemento-Organic Chemistry and Department of Chemistry, Nankai University, Tianjin 300071,
Peopleꢀs Republic of China
Fax : (+86)-22-2350-2458; e-mail: zhengjiehe@nankai.edu.cn
Received: January 27, 2007
Abstract: In this paper, the air-stable and readily atic comparison with other structurally similar N,P
available 1,3,5-triaza-7-phosphaadmantane (PTA) is catalysts, it is concluded that the superiority of PTA
reported as a practical and versatile nucleophilic in the above nucleophilic catalysis is attributable to
phosphine organocatalyst. Under the mediation of its comparable nucleophilicity with that of trialkyl-
15–30 mol% of PTA, various electrophiles like alde- phosphines. The feasibility to use PTA as an alterna-
hydes and imines readily undergo the Morita– tive catalyst in place of the air-sensitive trialkylphos-
Baylis–Hillman reactions with a variety of activated phines is also discussed.
olefins, giving the corresponding adducts in high
yields. In the phosphine-catalyzed [3+2] cycloaddi-
tion reaction of 4-substituted 2,3-butadienoates with Keywords: [3+2] cycloaddition reaction; Morita–
G
N-tosylimines, PTA is also proven to be a compara- Baylis–Hillman reaction; nucleophilic catalysis; terti-
ble catalyst as tributylphosphine (PBu3). By system- ary phosphines; 1,3,5-triaza-7-phosphaadamantane
Introduction
be promoted by a nucleophilic tertiary amine or phos-
phine. Since its discovery, it has been associated with
From the viewpoints of green chemistry, reduction of a number of problems, most notably, its sluggish reac-
the generation of polluting chemicals and of the use tion rate and high substrate-dependence of the yield.
of dangerous chemicals in the chemical process are In the last two decades, although significant progress
among the essential steps which must be taken to has been made on its efficiency and selectivity,[4] the
maintain the sustainability of the global environ- majority of the issues remain. As evidenced by the in-
ment.[1] Any optimization on or replacement for a creasing number of publications on this reaction, it is
current chemical manufacturing process, and innova- still a hot spot in the field of organic chemistry. Most
tion of new processes are fundamentally based on the of the research efforts have been directed towards the
availability of new and efficient synthetic reactions. following three aspects: exploring new catalysts to im-
Nowadays, many atom-economical reactions with prove its efficiency and selectivity, expanding its
enormous synthetic potentials have attracted much scope, and increasing its utility in organic synthesis.[5]
research effort, especially from organic chemists.[2]
Both tertiary amines and tertiary phosphines are
One of these important reactions is the Morita– the most often used catalysts in the MBH reaction,
Baylis–Hillman (MBH) reaction, which couples alde- even from early beginning. Compared to their amine
hydes with activated olefins in an atom-economical analogues, tertiary phosphines have better nucleophi-
fashion, giving densely functionalized allyl alcohol de- licity and weaker basicity; hence they often outper-
rivatives [Eq. (1)].[3] In general, this reaction needs to form their amine counterparts in nucleophilic cataly-
sis, as well as in MBH reactions. Currently, both
amine and phosphine catalysts are equally important
for the MBH reaction with respect to scope, efficiency
and selectivity.[5]
Recently, nucleophilic catalysis by tertiary phos-
phines has emerged as a powerful tool in synthetic or-
ganic chemistry as numerous phosphine-catalyzed
new reactions have been reported.[6] Since the nucleo-
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2007

Xiaofang Tang et al.
FULL PAPERS
philicity of trialkylphosphines is the strongest among of PTA as an alternative nucleophilic catalyst for air-
their amine analogues and triarylphosphines, trialkyl- sensitive trialkylphosphines, we disclose the PTA-cat-
phosphines are very often employed alone or in com- alyzed [3+2] cycloaddition reaction of 4-substituted
bination with other co-catalysts for enhanced activity, butadienoates with N-tosylimines in this paper.
especially in cases where greater nucleophilicity is re-
quired.[5i–k,r,7] However, unlike tertiary amines or triar-
ylphosphines, pure trialkylphosphines are highly air- Results and Discussion
sensitive and in some cases pyrophoric. Extra cautions
and manipulations must be therefore taken in their PTA-Catalyzed MBH Reactions with a Variety of
use. A few of precedent attempts were reported to Activated Olefins
address this air-sensitivity issue. Fu and co-workers[8]
suggested converting trialkylphosphines into their air- With 2-Cyclopenten-1-one
stable conjugate acids such as tetrafluoroborate, and
then releasing them in situ by treatment with an ap- Cyclic a,b-unsaturated ketones like cyclopentenone
propriate base. This simple and practical method has and cyclohexenone are often employed as substrates
been proven effective in a diverse set of reactions in- in the MBH reaction. In this work, 2-cyclopenten-1-
cluding the MBH reaction, although it carries some one was chosen for the PTA-catalyzed MBH reaction
obvious drawbacks such as involving extra manipula- as a cyclic activated olefin. 2-Cyclohexen-1-one was
tions. In another report,[9] several ferrocenyldialkyl- not used due to its toxicity. It is found that, under
phosphines, possessing simultaneously stability to air very mild conditions, PTA (15 mol%) can effectively
oxidation and high nucleophilicity, were disclosed as mediate the MBH reaction of aromatic aldehydes
effective catalysts for the MBH reaction between al- with 2-cyclopenten-1-one, giving the normal adducts
dehydes and acrylates.
in good to excellent yields (Table 1). In the cases of
As part of our continuous effort devoted to phos- more reactive aldehydes with a strong electron-with-
phine-catalyzed carbon-carbon bond forming reac- drawing group on the aromatic ring, such as nitro-sub-
tions, we have been engaged in the development of stituted aldehydes, a small amount (less than 5%) of
an air-stable and highly nucleophilic alternative for by-product 2 was isolated along with the major MBH
commonly used but extremely air-sensitive trialkyl- product 1 (Table 1, entries 2–4). Obviously, 2 resulted
phosphine catalyst such as PBu3. A readily available from the side aldol reaction of MBH product 1 with
cage-like trialkylphosphine, 1,3,5-triaza-7-phospha- the substrate aldehyde. A similar observation was re-
adamantane (PTA), is reported and its overall reactiv-
ity including nucleophilicity is comparable to those of
other pure trialkylphosphines except that it is air-
stable.[10] Its air-stability is even much higher than that
Table 1. PTA-catalyzed MBH reaction of aromatic alde-
of triphenylphosphine with respect to the kinetic con-
stants of oxidation.[11] This kind of unique property of
PTA prompted us to explore its potential utility as a
trialkylphosphine nucleophilic catalyst, although it
has been long used as a water-soluble ligand in coor-
dination chemistry.[10]
hydes with 2-cyclopenten-1-one.
In our preliminary communication,[12] we reported
PTA is highly efficient for the MBH reaction of both
aromatic and aliphatic aldehydes with activated al-
kenes ethyl (butyl) acrylates and methyl vinyl ketone
[Eq. (2)]. Herein, we further report the details of the
Entry Ar
Reaction Product[a] Yield[b] [%]
Time [h]
1
2
3
4
5
6
7
8
C6H5
24
20
20
6
24
24
1a
1b
1c
1d
1e
1f
1g
1h
47
80
87
97
60
53
54
63
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
3-FC6H4
2,4-Cl2C6H3
2-F-4-ClC6H3 24
2-furyl 24
[a]
Identified by 1 H, 13C NMR, and satisfactory microanaly-
sis obtained for new compounds 1e, 1f and 1g.
Isolated yield based on the substrate aldehyde.
PTA-catalyzed MBH reaction with a broad range of
activated olefins. Also, to demonstrate the feasibility
[b]
2008
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2007 – 2017

1,3,5-Triaza-7-phosphaadamantane (PTA)
FULL PAPERS
Table 3. PTA-catalyzed MBH reaction of aromatic alde-
hydes with acrolein.
ported by Shi in the PBu3-catalyzed MBH reaction of
aromatic aldehydes with 2-cyclopenten-1-one.[13]
With Acrylamide
Acrylamide is less reactive in the MBH reaction, pre-
sumably due to the electron delocalization of the lone
pair of electrons on the nitrogen atom of acrylamide
decreasing the electron-withdrawing capability of the
carbonyl group. As a consequence, few examples of
the use of acrylamide as an activated olefin in an effi-
cient MBH reaction were reported,[14] although its
MBH adduct is also versatile in organic synthesis. Up
to date, the most effective catalyst reported is 1,4-
Entry Ar
Reaction Time
[h]
Product[a] Yield[b]
[%]
1
2
3
4
2-
4
4a
4b
4c
4d
87
92
83
56
NO2C6H4
3-
NO2C6H4
4-
NO2C6H4
3-FC6H4
4
4
96
diazabicyclo[2.2.2]octane (DABCO) as a sole exam-
N
[a]
[b]
ple. Under the promotion of 50 mol%–100 mol% of
DABCO, a few of aromatic aldehydes gave the
normal MBH adducts with acrylamide in fair to excel-
lent yields.[14] This situation intrigued us to expand the
scope of the PTA-promoted MBH reaction to acryl-
amide. Our results show that PTA is also remarkably
Identified by 1 H, 13C NMR.
Isolated yield based on the substrate aldehyde.
effective for acrylamide, although only in the MBH self-polymerization, which is even more severe in the
reaction with aromatic aldehydes, and in some cases presence of a basic amine. Only a few of examples
suffering from longer reaction times and lower yields were reported with the yields of the adducts generally
(Table 2). Based on our data and those in reports,[14] it being low to fair.[15] Employing the highly reactive
should be concluded that PTA is comparable to electrophile polyfluoroaldehyde[15a] or high pressur-
DABCOin the MBH reaction with acrylamide in
terms of the scope, reaction time, and catalyst load- the self-polymerization to enhance the yield of the
e[15b] are among the effective means of diminishing
ing.
normal adduct. Most of the reported catalysts in the
MBH reaction with acrolein are tertiary amines in-
cluding DABCOas the best. Our attempt reveals that
PTA is pretty effective in the mediation of this reac-
tion. Under mild conditions, several reactive aromatic
With Acrolein
Acrolein is less often used as a substrate in the MBH aldehydes could readily give the normal MBH ad-
reaction, assumingly because of its susceptibility to ducts with acrolein in fair to good yields (Table 3).
However, less reactive aldehydes like benzaldehydes
with electron-donating substituents could not afford
the normal adducts in appreciable yields. Prolonged
reaction time did not help since side reactions like
polymerization of acrolein became severe. Despite
the limited scope, PTA is still among the best catalysts
for the MBH reaction with acrolein.
Table 2. PTA-catalyzed MBH reaction of aromatic alde-
hydes with acrylamide.
Entry Ar
Reaction Time Product[a] Yield[b]
PTA-Catalyzed Aza-MBH Reactions of Imines
[h]
[%]
The aza-MBH reaction is another version of the
MBH reaction with imines being employed as the
electrophilic substrate instead of aldehydes, affording
allylamine derivatives as the MBH adduct. Due to its
enormous synthetic potential, it has also received ex-
tensive studies in recent years.[5d,l–q,s,16] Both tertiary
amines and tertiary phosphines are effective catalysts
for aza-MBH reactions. In this work, we found that
PTA is also an efficient catalyst for aza-MBH reac-
tions of both N-tosyl- and N-thiophosphinoylimines
1
2
3
4
5
6
2-NO2C6H4
3
3
4
24
3a
3b
3c
3d
3e
3f
82
55
91
21
44
30
3-NO2C6H4
4-NO2C6H4
3-FC6H4
2,4-Cl2C6H3 24
2-F-4-
24
ClC6H3
[a]
[b]
Identified by 1 H, 13C NMR, and satisfactory microanaly-
sis obtained for new compounds 3d, 3e and 3f.
Isolated yield based on the substrate aldehyde.
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2009

Xiaofang Tang et al.
FULL PAPERS
The aza-MBH reaction of N-diphenylphosphinyli-
mines has been developed to take advantage of the
À
ease of the P N bond cleavage under acidic hydroly-
sis,[16a,d] since the activating group tosyl is difficult to
be removed from the corresponding aza-MBH prod-
ucts under mild conditions. To extend this successful
strategy to other phosphorus-activating groups, we ex-
plored the aza-MBH reactions of N-thiophosphoryl-
or N-thiophosphinylimines with activated olefins such
as methyl acrylate and MVK. Under the mediation of
PTA (10 mol%–30 mol%), these reactions proceed
smoothly, giving the corresponding N-thiophosphinoyl
adducts in good to excellent yields [Eq. (4)]. Removal
of the phosphorus groups from the aza-MBH prod-
ucts has been achieved via mild acidic alcoholysis, af-
fording the corresponding deprotected allylamines
with hydrolysis sensitive groups like esters remaining
intact. These results will be disclosed in detail in due
with activated alkenes [Eq. (3)and Eq. (4)]. Since course.
phosphine-promoted aza-MBH reactions have been
extensively studied for reactive N-tosylimines, herein
only a few representative N-tosylimines and activated Comparison with Other N,P Catalysts in the MBH
olefins were chosen to illustrate PTAꢀs effectiveness.
Reaction
In the reaction of N-tosylimine with methyl vinyl
ketone (MVK), an abnormal product, substituted di- In order to gain some insights into PTA nucleophilic
hydropyrole 6, forms competitively along with the catalysis, as well as its unique physical property, we
normal aza-MBH adduct 5 in fair to good combined surveyed five N,P compounds (Scheme 1) with a cer-
yield (Table 4). In Shiꢀs report,[16b] a similar reaction,
Table 4. Representative examples of PTA-catalyzed aza-
MBH reaction of N-tosylimine.
Entry Ar
EWG Reaction Yield of Yield of
Time [h] 5[a] [%] 6[a] [%]
1
2
3
4
5
6
C6H5
COMe 24
5a, 42
5b, 25
5c, 33
5d, 36
5e, 29
5f, 20
6a, 19
6b, 27
6c, 49
0
0
0
4-CH3C6H4 COMe 24
4-FC6H4
C6H5
4-CH3C6H4 CO2Et 48
4-FC6H4 CO2Et 48
COMe 24
CO2Et 48
Scheme 1. Selected N,P catalysts with structural similarity.
[a]
Isolated yield based on substrate imine.
tain similarity in structure to PTA in the MBH reac-
tion. In our previous communication,[12] on the basis
of the difference in catalytic activity between PTA
catalyzed by the weak nucleophilic Ph3P, exclusively and its nitrogen analogue hexamethylenetetramine
gives the normal aza-MBH product 5; in contrast, the (HMT), we concluded that PTA acts as a trialkylphos-
use of the strong nucleophilic Bu3P leads to the for- phine catalyst, and its superiority over its nitrogen
mation of 6 as one of major products. As concluded counterpart in the MBH reaction is attributed to its
by Shi, this chemoselectivity is attributed to the differ- better nucleophilicity. In this paper, we provide fur-
ence of the phosphines in nucleophilicity. These re- ther evidence in support of this conclusion. For a
sults also corroborate that the catalytic behaviour of series of aromatic aldehydes and activated olefins like
PTA is similar to that of trialkylphosphine like Bu3P. ethyl acrylate and MVK, PTA is obviously more effi-
In the case of ethyl acrylate, the aza-MBH reaction cient than HMT in the MBH reaction (Table 5).
exclusively gives the normal adducts 5 in moderate
yields (Table 4).
In the nucleophilic catalysis, the catalytic activity is
often consistent with nucleophilicity strength of the
2010
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2007 – 2017

1,3,5-Triaza-7-phosphaadamantane (PTA)
FULL PAPERS
Table 5. Comparison of activity between PTA and HMT in
the MBH reaction.[a]
Entry Ar
EWG Catalyst Time
[h]
Yield[b]
[%]
1
2
2-NO2C6H4
CO2Et PTA
HMT
CO2Et PTA
HMT
CO2Et PTA
HMT
CO2Et PTA
HMT
CO2Et PTA
HMT
COMe PTA
HMT
COMe PTA
HMT
COMe PTA
HMT
5
24
5
24
5
24
5
56
20
64
24
72
28
48
10
40
8
73
27
91
54
98
63
90
40
96
61
3-NO2C6H4
4-NO2C6H4
2,4-Cl2C6H3
2-F-4-ClC6H3
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2,4-Cl2C6H3
2-F-4-ClC6H3
Scheme 2. Generally accepted mechanism for the MBH re-
action.
3
4
24
5
5
24
0.5
0.5
0.5
0.5
0.5
0.5
5
6
7
8
9
COMe PTA
HMT
COMe PTA
HMT
5
3
3
10
Scheme 3. Formation of zwitterions with acrylate in aqueous
media.
[a]
Reaction conditions: aldehyde (1.0 mmol); for ethyl acry-
late (2 mL), reaction run solvent-free; for MVK
(3.0 mmol), reaction run in THF (2 mL).
[b]
Isolated yield of the corresponding MBH adduct.
sion of PTA into its corresponding zwitterions (PTA-
zwitterions);[12] however, in sharp contrast, no detect-
catalyst.[9,17] Nucleophilicity is one of the important able amount of such zwitterions was found by
factors affecting nucleophilic catalysis. Evaluation or 1H NMR from the reaction with HMT under similar
comparison on nucleophilicity is generally based on conditions (Scheme 3). These results clearly reflect
the reactivity of a nucleophile in certain nucleophilic the difference in nucleophilicity among PTA,
reactions such as nucleophilic substitution reactions.[18] DABCOand HMT, that is to say, the first two cata-
In light of generally accepted mechanism for the lysts are comparably nucleophilic, and the latter much
MBH reaction, the Michael addition of nucleophilic less nucleophilic. This order of the nucleophilicity for
catalyst to activated olefins, generating reactive eno- these three catalysts matches well the order of their
late intermediates, is the only step that involves the catalytic efficiency in the MBH reaction. Based on
nucleophilic attack of the catalyst in the whole cata- the reported data[20,21] and ours, the catalytic activities
lytic cycle (Scheme 2).[19] Accordingly, nucleophilicity for PTA and DABCOare generally on the same
of the catalyst in the MBH reaction could be evaluat- level, which is much higher than that of HMT. Thus,
ed by its reactivity in the Michael addition with acti- it should be concluded that the nucleophilicity of a
vated olefin. Previously, Hu et al.[20] reported that in- catalyst is vital to its efficiency in the nucleophilic cat-
cubation of methyl acrylate (3 mmol) with DABCO alysis, as well as in the MBH reaction.
(100 mol%) readily gave the corresponding zwitter-
Although there has been a commonly accepted
ions at room temperature in 1,4-dioxane-water (1:1, mechanism in place for the MBH reaction
v/v), which resulted from the Michael addition of (Scheme 2), much research interest has still been di-
DABCOto acrylate followed by hydrolysis of the
rected toward its re-evaluation and refinement.[19,22]
ester group (Scheme 3); in our study, incubation of Up to date, most of the evidence to support the cata-
PTA (2 mmol) with ethyl acrylate (6 mmol) for 6 h in lytic cycle is from kinetic studies including isotopic ef-
5 mL of THF-H2O(4:1, v/v) led to a 100% conver-
fects. There is only a single experimental finding pro-
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2011

Xiaofang Tang et al.
FULL PAPERS
Table 6. Comparuison of activity for selected air-stable N,P
catalysts in the MBH reaction.[a]
Entry Ar
EWG Catalyst
Time Yield[b]
[h]
[%]
1
4-NO2C6H4
CO2Et PTA
5
72
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
2-pyridyl
CO2Et PPh3
6
44
28
NR
trace
NR
98
55
63
NR
55
NR
63
trace
5
NR
NR
NR
73
70
6
NR
NR
NR
CO2Et HMT
CO2Et CH3-PTA
CO2Et acetyl-PTA
CO2Et TCP
COMe PTA
COMe PPh3
COMe HMT
COMe CH3-PTA
COMe acetyl-PTA
COMe TCP
CO2Et PTA
CO2Et PPh3
CO2Et HMT
CO2Et CH3-PTA
CO2Et acetyl-PTA
CO2Et TCP
COMe PTA
COMe PPh3
COMe HMT
COMe CH3-PTA
COMe acetyl-PTA
COMe TCP
24
72
72
72
0.5
5
Figure 1. X-ray crystal structure of PTA-zwitterions.
vided by X-ray crystallography of a trapped inter-
mediate from the DABCO-catalyzed MBH reaction
of salicylaldehyde with methyl acrylate.[23] In this
study, the reaction of PTA with ethyl acrylate in aque-
ous THF gave crystalline PTA-zwitterions, which was
recrystallized from a mixture of THF-methanol to
afford some single crystals suitable for X-ray crystal-
lography (Figure 1).[24] The crystal structure of PTA-
zwitterions does not only provide unambiguous evi-
dence for the nucleophilic attack of PTA taking place 18
at the phosphorus atom, it also verifies the Michael
addition step in the catalytic cycle.
In Scheme 1 are listed several N,P catalysts, which
are structurally in proximity to PTA. Among them,
N-methylated PTA iodide[25a] (CH3-PTA) and 3,7-di-
0.5
72
72
72
12
24
24
24
24
24
15
15
15
48
48
48
19
20
21
22
23
24
2-pyridyl
2-pyridyl
2-pyridyl
acetyl-1,3,7-triaza-5-phosphabicyclo
[3.3.1]nonane[25c]
N
[a]
Reaction conditions: aldehyde (1.0 mmol); for ethyl acry-
late (2 mL), reaction run solvent-free; for MVK
(3.0 mmol), reaction run in THF (2 mL).
(acetyl-PTA) are both air-stable derivatives of PTA.
The acyclic compounds tris(N,N-dimethylaminome-
thyl)phosphine[26] (TMP) and tris(carboxymethylami-
nomethyl)phosphine[27] (TCP) both incorporate a
[b]
Isolated yield of the corresponding MBH adduct.
À À À
phosphorus atom by the same linkages of P C N C
as PTA. TCP is reportedly air-stable. In contrast,
TMP could be considered the closest acyclic phos-
phine to PTA with regard to electron-effect, but it is
The air-sensitive phosphine TMP shows similar ac-
extremely air-sensitive (caution: spontaneous igni- tivity to PTA in the MBH reaction. Under the promo-
tion!). Certainly, the air stability of trialkylphosphine tion of 20 mol% of TMP, various aromatic aldehydes
is closely related to its specific structure. For the pur- readily give normal MBH adducts with the activated
pose of comparison with PTA, these four phosphines, olefins ethyl acrylate and acrylonitrile in fair to good
together with PPh3 and HMT, were surveyed for their yields (Table 7). However, the TMP-mediated reac-
catalytic activity in the MBH reaction with active aro- tion of aromatic aldehyde with MVK is pretty compli-
matic aldehydes (Table 6 and Table 7).
cated. No expected MBH product could be isolated
As shown in Table 6, the weakly nucleophilic cata- from the reaction mixture in an appreciable amount,
lysts PPh3 and HMT are both moderately effective in except that a dimer of MVK and its intramolecular
the selected reactions, but clearly less efficient than aldol condensation product were obtained in about
PTA (entries 1–3, 7–9, 13–15, 19–21). CH3-PTA and 30% overall yield [Eq. (5)]. In a similar fashion, ethyl
acetyl-PTA were reported to be poorer nucleophiles
than the parent PTA, although they could still be
used as phosphine ligands in the transition metal com-
plexes.[10] Consequently, both of the compounds are
almost ineffective in the MBH reaction. Likewise,
TCP does not show any catalytic activity in this study
(Table 6).
2012
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2007 – 2017

1,3,5-Triaza-7-phosphaadamantane (PTA)
FULL PAPERS
Table 7. P
aldehydes.
A
Table 8. PTA-catalyzed [3+2] cycloaddition reaction of 4-
substituted 2,3-butadienoates with imines.
Entry
Ar
EWG
Time [h]
Yield[a] [%]
1
2
3
4
5
6
7
8
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2,4-Cl2C6H3
2-FC6H4
3-FC6H4
4-FC6H4
C6H5
4-CH3C6H4
2-pyridyl
2-furyl
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-pyridyl
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CN
12
4
84
60
80
66
65
70
61
50
36
24
36
29
20
15
38
Entry R
Ar
Reaction
Time [h]
Product[a] Yield[b]
[%]
12
36
12
12
12
24
24
24
24
12
12
12
24
1
Me
C6H5
25
6
1
5
4
7a
7b
7c
7d
7e
7f
7g
7h
7i
73
96
89
90
90
84
75
86
97
99
95
65
89
57
94
99
99
70
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Me
Me
Ph
4-CH3C6H4
4-ClC6H4
2-ClC6H4
4-FC6H4
4-CH3OC6H4 22
2-furyl
3-pyridyl
4-FC6H4
4-ClC6H4
2-ClC6H4
9
21
2
4
2
2
10
11
12
13
14
15
10
11
12
13
14
15
16
17
18
Ph
Ph
Ph
7j
7k
7l
CN
CN
CN
4-CH3OC6H4 20
t-Bu 4-ClC6H4
t-Bu 2-ClC6H4
t-Bu 4-FC6H4
t-Bu 4-CH3OC6H4
t-Bu 2-furyl
13
15
6
3
4
7m
7n
7o
7p
7q
7r
[a]
Isolated yield based on aldehyde.
t-Bu 3-pyridyl
2
[a]
Identified by 1 H, 13C NMR, and satisfactory microanaly-
sis obtained for new compounds 7d, 7j, 7 m, 7q and 7r.
Isolated yield based on the substrate imine.
acrylate could undergo the same coupling under the
mediation of TMP (2 mol%).
[b]
PTA-Catalyzed [3 + 2] Cycloaddition Reaction of 4-
Substituted 2,3-Butadienoates with Imines
The nucleophilic phosphine-catalyzed [3+2] cycload- [3+2] cycloaddition reaction requiring a highly nucle-
dition reactions of 2,3-butadienoates or 2-alkynoates ophilic catalyst. Our results show that under the medi-
with the dipolarophiles such as acrylates, acrylonitrile, ation of 20 mol% of PTA, all three 4-substituted 2,3-
and N-tosylimines, provide a powerful tool for the butadienoates (R=Me, Ph, t-Bu) readily undergo
preparation of cyclopentene derivatives and pyrro- [3+2] cycloaddition reactions with a series of aromat-
lines.[6,17,28] For a reactive dipolar precursor like ethyl ic N-tosylimines. The normal cycloaddition products
1
butadienoate, the weakly nucleophilic catalyst Ph3P with the cis configuration, as verified by their H and
works well in some [3+2] cycloaddition reactions 13C NMR spectra together with corroboration of the
with various activated olefins.[6a] But in such cycload- reported data,[17,28d] were exclusively obtained in good
dition reactions of less reactive substituted 2,3-buta- to excellent yields (Table 8). With regards to reaction
dienoates or 2-alkynoates, as well as in intramolecular time, selectivity and yield, PTAꢀs efficiency in this cat-
cycloaddition reactions, a more nucleophilic catalyst, alysis is definitely comparable with that of PBu3 as
most likely PBu3, is most often used.[6b,17,28] In princi- shown in the previous report by Kwon.[17] Thus, PTA
ple, tertiary amines like triethylamine, DABCO, and should be a preferred catalyst in this type of cycload-
DMAP are ineffective in the catalysis of the cycload- dition reaction regarding its superior air stability over
ditions.[6]
As illustrated in the MBH reaction, the high effi-
ciency of PTA as a nucleophilic catalyst intrigued us
other trialkylphosphines.
to explore its use in the above [3+2] cycloaddition Conclusions
reactions as an alternative for air-sensitive trialkyl-
phosphine catalysts like PBu3. Thus, the less reactive In this work, we have demonstrated that the air-stable
ethyl 4-substituted 2,3-butadienoates and aromatic N- and readily available PTA is a practical and versatile
tosylimines were selected as the substrates for the nucleophilic phosphine catalyst for both MBH reac-
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2013

Xiaofang Tang et al.
FULL PAPERS
1
1e: viscous oil; H NMR (CDCl3): d=7.30–6.80 (m, 5H),
5.43 (s, 1H), 3.85 (br s, 1H), 2.50 (m, 2H), 2.33 (m, 2H);
13C NMR (CDCl3): d=209.3, 162.9 (d, J=244.4 Hz), 159.7,
147.4, 144.2 (d, J=7.0 Hz), 129.9 (d, J=8.0 Hz), 121.9 (d,
J=3.3 Hz), 114.6 (d, J=21.1 Hz), 113.2 (d, J=22.0 Hz),
68.8, 35.1, 26.7; anal. calcd. for C12H11FO2: C 69.89, H 5.38;
found: C 69.70, H 5.45.
tion with a broad scope and [3+2] cycloaddition reac-
tion of less reactive substituted allenoates. Its high ef-
ficiency in the catalysis is certainly attributable to its
superior nucleophilicity originating from the phospho-
rus atom. As evidenced by the facts that the overall
reactivity, including nucleophilicity, of PTA are com-
parable to those of pure but air-sensitive trialkylphos-
phines, and also, as proven in this study, that PTA is
almost equally effective as the trialkylphosphine cata-
lyst PBu3 in the [3+2] cycloaddition reaction, it is
safe to say that PTA could be used as a preferable al-
ternative for air-sensitive trialkylphosphine in nucleo-
philic catalysis, which requires a strong nucleophilic
catalyst. Since trialkylphosphines have received in-
creasing interest in nucleophilic catalysis due to the
enhanced activity over their triarylphosphine or trial-
kylamine counterparts, we anticipate that PTA will
gain more popularity as a practical and versatile nu-
cleophilic phosphine organocatalyst in the future.
1
1f: viscous oil; H NMR (CDCl3): d=7.50 (d, J=8.4 Hz,
1H), 7.27 (d, J=2.1 Hz, 1H), 7.21 (dd, J=8.4, 2.1 Hz, 1H),
7.06 (m, 1H), 5.78 (s, 1H), 4.10 (br s, 1H), 2.51 (m, 2H),
2.38 (m, 2H); 13C NMR (CDCl3): d=209.6, 160.2, 145.3,
137.4, 133.8, 132.5, 129.0, 128.8, 127.4, 65.8, 35.1, 26.6; anal.
calcd. for C12H10Cl2O2: C 56.06, H 3.92; found: C 55.89, H
4.05.
1
1g: viscous oil; H NMR (CDCl3): d=7.34–7.18 (m, 3H),
7.12 (dd, J=9.9, 2.1 Hz, 1H), 5.67 (s, 1H), 4.15 (br s, 1H),
2.52 (m, 2H), 2.36 (m, 2H); 13C NMR (CDCl3): d=209.3,
159.8, 159.2 (d, J=249.8 Hz), 145.6, 129.2 (d, J=4.4 Hz),
127.8 (d, J=13.5 Hz), 127.5 (d, J=3.8 Hz), 121.6 (d, J=
9.7 Hz), 118.8 (d, J=24.5 Hz), 63.4, 35.0, 26.6; anal. calcd.
for C12H10ClFO2: C 59.89, H 4.19; found: C 59.77, H 4.34.
PTA-Catalyzed MBH Reaction of Aromatic
Aldehydes with Acrylamide; General Procedure
Experimental Section
A mixture of aromatic aldehyde (1.0 mmol), acrylamide
(3.0 mmol), and PTA (0.2 mmol) in anhydrous THF (2 mL)
was stirred at room temperature for the time listed in
Table 2. Then the reaction mixture was concentrated on a
rotary evaporator, and the residue was taken up in ethyl
acetate (25 mL) and washed with saturated brine (10 mL).
The aqueous layer was extracted with dichloromethane (2”
10 mL). The extractings were combined with ethyl acetate
layer, and dried over anhydrous sodium sulfate. After filtra-
tion and evaporation of solvent, the crude product was puri-
fied by column chromatography on silica gel (petroleum
ether-ethyl acetate 3 : 1 as eluant) to afford pure product 3.
General Remarks
Unless otherwise noted, all catalytic reactions were carried
out in the ambient atmosphere. Commercially available
chemicals were used as received. PTA was prepared from
tetrahydroxymethylphosphonium sulfate according to a pre-
vious procedure.[29] Other phosphorus catalysts were pre-
pared as reported in the literature. 4-Substituted 2,3-buta-
dienoates[30] and N-tosyl- and N-thiophosphinoylimines[31]
were also prepared as described in the literature.
Nuclear magnetic resonance spectra (1H, 13C, and 31P)
were recorded on Bruker 300 MHz and Variant 400 MHz
NMR spectrometers using TMS as internal standard (1H,
13C) and 85% phosphoric acid as external standard (31P),
with CDCl3 as solvent, unless otherwise mentioned. Elemen-
tal analyses were performed on a Yanaco CHN Corder MT-
3 automatic analyzer. ESI mass spectra were recorded with
a ThermoFinnigan LCQ Advantage LC-MS. X-Ray crystal
diffraction data were collected on a Nonius Kappa CCD dif-
fractometer with Mo Ka radiation (l=0.7107 Š) at room
temperature.
1
˚
3d: off-white solid, mp 117–119 C; H NMR (DMSO-d6):
d=8.87 (m, 1H), 7.45–7.20 (m, 4H), 6.52 (br s, 1H), 6.35–
6.16 (m, 3H), 5.65 (m, 1H); 13C NMR (DMSO-d6): d=
163.7, 162.2 (d, J=223.3 Hz), 145.0, 131.5, 130.0 (d, J=
7.0 Hz), 126.1, 122.0, 114.2 (d, J=16.0 Hz), 112.5 (d, J=
16.0 Hz), 72.2; anal. calcd. for C10H10FNO2: C 61.53, H 5.16,
N 7.16; found: C 61.35, H 5.24, N 7.01.
1
3e: H NMR (DMSO-d6): d=8.80 (m, 1H), 7.75–7.49 (m,
3H), 6.62 (br s, 1H), 6.49 (m, 1H), 6.18 (m, 2H), 5.64 (m,
1H); 13C NMR (DMSO-d6): d=163.7, 138.3, 133.0, 132.4,
131.3, 129.1, 128.5, 127.1, 126.2, 70.0; anal. calcd. for
C10H9Cl2NO2: C 48.81, H 3.69, N 5.69; found: C 48.64, H
3.81, N 5.45.
PTA-Catalyzed MBH Reaction of Aromatic
Aldehydes with 2-Cyclopenten-1-one; General
Procedure
1
3f: H NMR (DMSO-d6): d=8.88 (m, 1H), 7.60–7.46 (m,
3H), 6.59 (br s, 1H), 6.49 (m, 1H), 6.30–6.13 (m, 2H), 5.65
(m, 1H); 13C NMR (DMSO-d6): d=163.5, 161.9 (d, J=
241.6 Hz), 157.8, 131.3, 129.3, 127.2, 126.3, 121.1 (d, J=
9.7 Hz), 118.5 (d, J=18.2 Hz), 67.6; anal. calcd. for
C10H9ClFNO2: C 52.30, H 3.95, N 6.10; found: C 52.12, H
4.05, N 5.97.
A mixture of aromatic aldehyde (1.0 mmol), 2-cyclopenten-
1-one (1.5 mmol), and PTA (0.15 mmol) in THF-H2O
(2 mL, 4:1, v/v) was stirred at room temperature for the
time listed in Table 1. Then the volatile components were
removed on a rotary evaporator, and the residue was mixed
with dichloromethane (20 mL), washed twice with water
(2”5 mL), and dried over anhydrous sodium sulfate. After
filtration and evaporation of solvent, the crude product was
purified by column chromatography on silica gel (petroleum
ether-ethyl acetate, gradient elution) to afford pure product
1.
2014
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2007 – 2017

1,3,5-Triaza-7-phosphaadamantane (PTA)
FULL PAPERS
7j: colorless crystalline solid; mp 104–106 8C; 1H NMR
(CDCl3): d=7.48–7.01 (m, 13H), 6.70 (br s, 1H), 6.29 (br s,
1H), 5.74 (m, 1H), 3.90 (m, 2H), 2.27 (s, 3H), 0.96 (t, J=
7.8 Hz, 3H); 13C NMR (CDCl3): d=161.6, 143.6, 139.5,
138.6, 137.5, 134.3, 134.0, 129.4, 129.3, 128.9, 128.6, 128.1,
127.7, 127.3, 126.8, 69.7, 65.1, 60.9, 21.4, 13.6; ESI-MS:
m/z=482 and 484 (approximate ratio of isotopic peak inten-
sities is 2:1), calcd. for C26H25ClNO4S [M + 1]+: 482 and 484.
PTA-Catalyzed MBH Reaction of Aromatic
Aldehydes with Acrolein; General Procedure
A
mixture of aromatic aldehyde (1.0 mmol), acrolein
(2.0 mmol), and PTA (0.2 mmol) in THF (2 mL) was stirred
at room temperature for the time given in Table 3. Then the
reaction mixture was subjected to similar work-up and pu-
rification by silica gel column chromatography as described
in the general procedure for compounds 1 to give pure prod-
uct 4.
1
7m: colorless crystalline solid; mp 122–124 8C; H NMR
(CDCl3): d=7.70 (d, J=8.0 Hz, 2H), 7.36 (d, J=8.0 Hz,
2H), 7.25 (m, 4H), 6.73 (d, J=2.8 Hz, 1H), 5.81 (s, 1H),
4.33 (d, J=2.8 Hz, 1H), 4.10 (q, J=7.2 Hz, 2H), 2.38 (s,
3H), 1.13 (t, J=7.2 Hz, 3H), 0.79 (s, 9H); 13C NMR
(CDCl3): d=162.4, 144.0, 141.6, 138.3, 133.8, 133.7, 133.4,
129.6, 129.5, 128.1, 127.9, 77.8, 67.8, 60.9, 35.8, 27.8, 21.4,
13.9; anal. calcd. for C24H28ClNO4S: C 62.39, H 6.11, N 3.03;
found: C 62.21, H 6.29, N 2.94.
PTA-Catalyzed Aza-MBH Reaction of N-Tosylimines
with Methyl Vinyl Ketone or Ethyl Acrylate; General
Procedure
To
a mixture of N-tosylimine (1.0 mmol) and PTA
(0.2 mmol) in CH2Cl2 (2 mL, redistilled after refluxing with
CaH2) was added methyl vinyl ketone or ethyl acrylate
(3.0 mmol) in one portion. The resulting mixture was stirred
at room temperature for the time given in Table 4. Then the
reaction mixture was subjected to similar work-up and pu-
rification by silica gel column chromatography as described
in the general procedure for compounds 1 to give pure prod-
ucts 5 and 6.
7q: colorless crystalline solid; mp 89–90 8C; 1H NMR
(CDCl3): d=7.67 (d, J=8.4 Hz, 2H), 7.25 (m, 3H), 6.73 (m,
1H), 6.26 (dd, J=3.2, 1.6 Hz, 1H), 6.19 (d, J=3.2 Hz, 1H),
5.81 (s, 1H), 4.44 (m, 1H), 4.04 (m, 2H), 2.36 (s, 3H), 1.11
(t, J=7.2 Hz, 3H), 0.88 (s, 9H); 13C NMR (CDCl3): d=
161.8, 152.0, 143.8, 141.6, 140.7, 134.5, 131.9, 129.5, 127.8,
110.4, 108.7, 77.0, 63.2, 60.6, 36.2, 27.3, 21.4, 13.8; anal.
calcd. for C22H27NO5S: C 63.29, H 6.52, N 3.35; found: C
63.15, H 6.47, N 3.36.
A
7r: colorless crystalline solid; mp 103–104 8C; 1H NMR
(CDCl3): d=8.48 (m, 2H), 7.93 (m, 1H), 7.70 (d, J=8.0 Hz,
2H), 7.25 (m, 3H), 6.75 (br s, 1H), 5.83 (s, 1H), 4.34 (m,
1H), 4.08 (q, J=7.2 Hz, 2H), 2.38 (s, 3H), 1.12 (t, J=
7.2 Hz, 3H), 0.78 (s, 9H); 13C NMR (CDCl3): d=162.1,
148.8, 144.2, 142.0, 136.2, 135.6, 133.5, 133.0, 129.7, 127.9,
123.1, 77.9, 66.6, 61.0, 35.9, 27.8, 21.4, 13.9; anal. calcd. for
C23H28N2O4S: C 64.46, H 6.58, N 6.54; found: C 64.37, H
6.38, N 6.35.
Aldehydes with Acrylate or acrylonitrile; General
Procedure
Under the nitrogen atmosphere, to a solution of aldehyde
(1.0 mmol) in 2.0 mL of ethyl acrylate or acrylonitrile was
added (Me2NCH2)3P (0.2 mmol), and the resulting mixture
was stirred at room temperature for the specified time
(Table 7). Then the volatile components were removed on a
rotary evaporator, and the residue was taken up in ethyl
acetate (25 mL), washed with saturated brine and dried over
anhydrous sodium sulfate. After filtration and evaporation
of solvent, the crude product was purified by column chro-
matography on silica gel (petroleum ether-ethyl acetate 6:1
as eluant) to afford pure MBH product.
Acknowledgements
Financial support from National Natural Science Foundation
of China (Grant No. 20672057; 20421202), Scientific Re-
search Foundation of State Education Ministry for the Re-
turned Overseas Chinese Scholars, and Research Starting
Fund of Nankai University is gratefully acknowledged.
PTA-Catalyzed [3 + 2] Cycloaddition Reaction of 4-
Substituted 2,3-Butadienoates with Imines; General
Procedure
To
a mixture of N-tosylimine (1.0 mmol) and PTA
(0.2 mmol) in THF (2 mL) was added 4-substituted 2,3-buta-
dienoate (1.2 mmol). The resulting mixture was stirred at
room temperature till the imine was completely consumed References
(monitored by TLC). Then the solvent was removed on a
rotary evaporator, and the crude product was subjected to
separation by silica gel column chromatography (petroleum
ether - ethyl acetate, gradient elution), giving the corre-
sponding cycloaddition product 7.
[1] R. Mestres, Environ. Sci. & Pollut. Res. 2005, 12, 128–
132.
[2] For typical examples, see: a) B. M. Trost, Acc. Chem.
Res. 2002, 35, 695–705; b) T. V. RajanBabu, Chem.
Rev. 2003, 103, 2845–2860; c) B. Breit, Acc. Chem. Res.
2003, 36, 264–275.
[3] a) K. Morita, Z. Suzuki, H. Hirose, Bull. Chem. Soc.
Jpn. 1968, 41, 2815; b) A. B. Baylis, M. E. D. Hillman,
German Patent 2,155,113, 1972; Chem. Abstr. 1972, 77,
34174q.
7d: colorless crystalline solid; mp 118–122 8C; 1H NMR
(CDCl3): d=7.74 (d, J=8.4 Hz, 2H), 7.32–7.10 (m, 6H),
6.64 (br s, 1H), 6.15 (br s, 1H), 4.74 (m, 1H), 3.95 (m, 2H),
2.39 (s, 3H), 1.68 (d, J=6.6 Hz, 3H), 1.04 (t, J=7.2 Hz,
3H); 13C NMR (CDCl3): d=161.6, 143.6, 141.0, 138.0, 134.5,
134.1, 133.7, 129.6, 129.3, 129.1, 128.7, 127.8, 126.9, 65.4,
62.9, 60.8, 22.7, 21.4, 13.7; anal. calcd. for C21H22ClNO4S: C
60.06, H 5.28, N 3.34; found: C 60.26, H 5.25, N 3.35.
[4] For reviews, see: a) E. Ciganek, Organic Reactions
1997, 51, 201–350; b) J. Cai, Z. Zhou, C. Tang, Huaxue
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2015

Xiaofang Tang et al.
FULL PAPERS
Yanjiu 2001, 12, 54–64; c) D. Basavaiah, A. J. Rao, T.
Satyanarayana, Chem. Rev. 2003, 103, 811–892.
[12] Z. He, X. Tang, Y. Chen, Z. He, Adv. Synth. Catal.
2006, 348, 413–417.
[5] For most recent amine-catalyzed MBH reactions, see:
a) A. Berkessel, K. Roland, J. M. Neudorfl, Org. Lett.
2006, 8, 4195–4198; b) J. Wang, H. Li, X. Yu, L. Zu, W.
Wang, Org. Lett. 2005, 7, 4293–4296; c) C. E. Aroyan,
M. M. Vasbinder, S. J. Miller, Org. Lett. 2005, 7, 3849–
3851; d) K. Matsui, S. Takizawa, H. Sasai, J. Am. Chem.
Soc. 2005, 127, 3680–3681; e) S. Luo, P. G. Wang, J.
Cheng, J. Org. Chem. 2004, 69, 555–558; f) P. R. Krish-
na, V. Kannan, P. V. N. Reddy, Adv. Synth. Catal. 2004,
346, 603–606; g) Y. Hayashi, T. Tamura, M. Shoji, Adv.
Synth. Catal. 2004, 346, 1106–1110; h) Y. Sohtome, A.
Tanatani, Y. Hashimoto, K. Nagasawa, Tetrahedron
Lett. 2004, 45, 5589–5592; for most recent phosphine-
catalyzed MBH reactions, see: i) N. T. McDougal, S. E.
Schaus, J. Am. Chem. Soc. 2003, 125, 12094–12095;
j) N. T. McDougal, W. L. Trevellini, S. A. Rodgen, L. T.
Kliman, S. E. Schaus, Adv. Synth. Catal. 2004, 346,
1231–1240; k) M. E. Krafft, T. F. N. Haxell, J. Am.
Chem. Soc. 2005, 127, 10168–10169; l) P. Buskens, J.
Klankermayer, W. Leitner, J. Am. Chem. Soc. 2005,
127, 16762–16763; m) M. Shi, L.-H. Chen, C.-Q. Li, J.
Am. Chem. Soc. 2005, 127, 3790–3800; n) M. Shi, L.-H.
Chen, Pure Appl. Chem. 2005, 77, 2105–2110; o) M.
Shi, C.-Q. Li, Tetrahedron: Asymmetry 2005, 16, 1385–
1391; p) J. Gao, G.-N. Ma, Q.-J. Li, M. Shi, Tetrahedron
Lett. 2006, 47, 7685–7688; q) R. Gausepohl, P. Buskens,
J. Kleinen, A. Bruckmann, C. W. Lehmann, J. Klanker-
mayer, W. Leitner, Angew. Chem. Int. Ed. 2006, 45,
3689–3692; r) M. E. Krafft, J. A. Wright, Chem.
Commun. 2006, 2977–2979; s) Y.-H. Liu, L.-H. Chen,
M. Shi, Adv. Synth. Catal. 2006, 348, 973–979; for ap-
plication examples in organic synthesis, see: t) P. J.
Dunn, M. L. Hughes, P. M. Searle, A. S. Wood, Org.
Proc. Res. Dev. 2003, 7, 244–253; u) B. Das, J. Bane-
rjee, N. Chowdhury, A. Majhi, G. Mahender, Helv.
Chim. Acta 2006, 89, 876–883; v) S. A. Rodgen, S. E.
Schaus, Angew. Chem. Int. Ed. 2006, 45, 4929–4932.
[6] For reviews, see: a) X. Lu, C. Zhang, Z. Xu, Acc.
Chem. Res. 2001, 34, 535–544; b) J. L. Methot, W. R.
Roush, Adv. Synth. Catal. 2004, 346, 1035–1050; for
most recent examples of phosphine-catalyzed new reac-
tions, see: c) C.-K. Jung, J.-C. Wang, M. J. Krische, J.
Am. Chem. Soc. 2004, 126, 4118–4119; d) X.-F. Zhu,
A.-P. Schaffner, R. C. Li, O. Kwon, Org. Lett. 2005, 7,
2977–2980; e) R. P. Wurz, G. C. Fu, J. Am. Chem. Soc.
2005, 127, 12234–12235; f) V. Nair, A. T. Biju, K. Mo-
hanan, E. Suresh, Org. Lett. 2006, 8, 2213–2216;
g) N. T. McDougal, S. E. Schaus, Angew. Chem. Int. Ed.
2006, 45, 3117–3119; h) D. J. Wallace, R. L. Sidda,
R. A. Reamer, J. Org. Chem. 2007, 72, 1051–1054.
[7] G. E. Keck, D. S. Welch, Org. Lett. 2002, 4, 3687–3690.
[8] M. R. Netherton, G. C. Fu, Org. Lett. 2001, 3, 4295–
4298.
[13] M. Shi, Y.-M. Xu, G.-L. Zhao, X.-F. Wu, Eur. J. Org.
Chem. 2002, 3666–3679.
[14] a) C. Yu, L. Hu, J. Org. Chem. 2001, 67, 219–223;
b) P. R. Krishna, A. Manjuvani, V. Kannan, G. V. M.
Sharma, Tetrahedron Lett. 2004, 45, 1183–1185; c) C.
Faltin, E. M. Fleming, S. J. Connon, J. Org. Chem. 2004,
69, 6496–6499.
[15] a) M. V. Ram Reddy, M. T. Rudd, P. V. Ramachandran,
J. Org. Chem. 2002, 67, 5382–5385; b) J. S. Hill, N. S.
Isaacs, Tetrahedron Lett. 1986, 27, 5007–5010; c) P. T.
Kaye, X. W. Nocanda, J. Chem. Soc., Perkin Trans. 1
2002, 1318–1323.
[16] a) S. Kawahara, A. Nakano, T. Esumi, Y. Iwabuchi, S.
Hatakeyama, Org. Lett. 2003, 5, 3103–3105; b) M. Shi,
Y.-M. Xu, Eur. J. Org. Chem. 2002, 696–701; c) M. Shi,
Y.-M. Xu, Angew. Chem. Int. Ed. 2002, 41, 4507–4510;
d) M. Shi, G.-L. Zhao, Adv. Synth. Catal. 2004, 346,
1205–1219.
[17] X.-F. Zhu, C. E. Henry, O. Kwon, Tetrahedron 2005, 61,
6276–6282.
[18] a) W. A. Henderson, C. A. Streuli, J. Am. Chem. Soc.
1960, 82, 5791; b) W. A. Henderson, S. A. Buckler, J.
Am. Chem. Soc. 1960, 82, 5794; c) R. G. Pearson, H.
Sobel, J. Songstad, J. Am. Chem. Soc. 1968, 90, 319.
[19] L. S. Santos, C. H. Pavam, W. P. Almeida, F. Coelho,
M. N. Eberlin, Angew. Chem. Int. Ed. 2004, 43, 4330–
4333, and references cited therein.
[20] C. Yu, B. Liu, L. Hu, J. Org. Chem. 2001, 66, 5413–
5418.
[21] R. O. M. A. de Souza, B. A. Meireles, L. C. S. Aguiar,
M. L. A. A. Vasconcellos, Synthesis 2004, 1595–1600.
[22] For most recent reports, see: a) K. E. Price, S. J. Broad-
water, B. J. Walker, D. T. McQuade, J. Org. Chem.
2005, 70, 3980–3987; b) V. K. Aggarwal, S. Y. Fulford,
G. C. Lloyd-Jones, Angew. Chem. Int. Ed. 2005, 44,
1706–1708.
[23] S. E. Drewes, O. L. Njamela, N. D. Emslie, N. Ramesar,
J. S. Field, Synth. Commun. 1993, 23, 2807–2815.
[24] Selected crystal data for PTA-zwitterions (CCDC
634822): C9H20N3O4P (including 2 molecules of water),
M=265.25, monoclinic, space group P21/n, a=
10.025(2),
b=10.187(2),
(000)=568, Z=4, 1cald =1.449 gcmÀ3, U=
(Mo-Ka)=0.7107 Š, 6688
reflections collected in the range of 2.22 ꢀ q ꢀ 26.358,
c=12.842(2) Š,
b=
112.001(3)8, F
ACHTREUNG
1216.0(4) Š3, T=294(2) K, l
ACHTREUNG
R
int =0.0295. The structure was solved by different
methods and refinement, based on F2, was by full-
matrix least-squares to R1=0.0526, wR2=0.1056. The
supplementary crystallographic data for this compound
can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data request/cif0.
[25] a) D. J. Daigle, A. B. Pepperman Jr., J. Heterocycl.
Chem. 1975, 12, 579; b) V. I. Siele, J. Heterocycl. Chem.
1977, 14, 337; c) D. J. Darensbourg, C. G. Ortiz, J. W.
Kamplain, Organometallics 2004, 23, 1747–1754.
[26] H. Coates, P. A. Theodore Hoye, British Patent
842,593, 1960.
[9] S. I. Pereira, J. Adrio, A. M. S. Silva, J. C. Carretero, J.
Org. Chem. 2005, 70, 10175–10177.
[10] A. D. Phillips, L. Gonsalvi, A. Romerosa, F. Vizza, M.
Peruzzini, Coordination Chem. Rev. 2004, 248, 955–
993.
[11] M. M. Abu-Omar, J. H. Espenson, J. Am. Chem. Soc.
1995, 117, 272–280.
[27] D. E. Berning, K. V. Katti, C. L. Barnes, W. A. Volkert,
J. Am. Chem. Soc. 1999, 121, 1658–1664.
2016
asc.wiley-vch.de
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2007 – 2017

1,3,5-Triaza-7-phosphaadamantane (PTA)
FULL PAPERS
[28] For most recent reports, see: a) Y. Du, X. Lu, J. Org.
Chem. 2003, 68, 6463–6465; b) J.-C. Wang, S.-S. Ng,
M. J. Krische, J. Am. Chem. Soc. 2003, 125, 3682–3683;
c) J.-C. Wang, M. J. Krische, Angew. Chem. Int. Ed.
2003, 42, 5855–5857; d) G.-L. Zhao, M. Shi, J. Org.
Chem. 2005, 70, 9975–9984; e) L. Jean, A. Marinetti,
Tetrahedron Lett. 2006, 47, 2141–2145; f) J. E. Wilson,
G. C. Fu, Angew. Chem. 2006, 45, 1426–1429.
[29] D. J. Daigle, Inorg. Synth. 1998, 32, 40.
[30] R. W. Lang, H.-J. Hansen, Org. Synth. 1984, 22, 202.
[31] a) B. E. Love, P. S. Raje, T. C. Williams, Synlett 1994,
493; b) A. Zwierzak, A. N. Napieraj, Tetrahedron 1996,
52, 8789–8794.
Adv. Synth. Catal. 2007, 349, 2007 – 2017
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2017