Unusual nitrogen based heterocycles via allenic intermediates from the reaction of propargyl alcohols with P(III) substrates

Article abstract of DOI:10.1016/j.tet.2014.02.064

The apparently simple reaction of the P(III) precursors [(RNH)P(μ-N-t-Bu)₂PY] (Y=NH-t-Bu, Cl), (OCH₂CMe ₂CH₂O)PCl, and Ph₂PCl with functionalized propargyl alcohols is examined. In most cases, the fin

Full text of DOI:10.1016/j.tet.2014.02.064

Tetrahedron 70 (2014) 2643e2653
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Unusual nitrogen based heterocycles via allenic intermediates
from the reaction of propargyl alcohols with P(III) substrates
*
G. Gangadhararao, K.C. Kumara Swamy
School of Chemistry, University of Hyderabad, Hyderabad 500 046, A.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
The apparently simple reaction of the P(III) precursors [(RNH)P(
m
-N-t-Bu)2PY] (Y¼NH-t-Bu, Cl),
Received 20 December 2013
Received in revised form 14 February 2014
Accepted 24 February 2014
Available online 3 March 2014
(OCH2CMe2CH2O)PCl, and Ph2PCl with functionalized propargyl alcohols is examined. In most cases, the
final products are not the expected allenes but several previously unpredicted structural motifs, such as
substituted oxazabenzocycloheptenones, indolinones, and fused heterocycles as revealed by X-ray
crystallography. Mechanistic aspects of these novel reactions, as well as possible utility and the structural
chemistry of the products are also discussed. The PeC or PeN bond cleavage of many of these com-
pounds led to phosphorus-free 2-substituted indoles, quinolinones, and tetrahydroacridine.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Allenes
Fused-ring systems
Indoles
Indolinones
Quinolinones
1. Introduction
transformations involving P(III) species as one of the components,8
and to generate a diverse range of coordination complexes.9 The
The reaction of propargyl alcohols R0C^CCH2OH with R2P(III)e
Cl compounds constitutes a facile route to allenylphosphonates/
allenylphosphine oxides R2P(O)C(R0)¼C]CH2 via a pseudo-Claisen
rearrangement of the initially formed P(III) compounds
R2P(OCH2C^CR0).1 A large number of synthetically useful phos-
phorus (and analogous sulfur) based allenes (cf. compound 1,
Scheme 1a), can be conveniently synthesized by this method.1d
Allenes, including these allenylphosphonates, are valuable syn-
thons and hence their synthesis and reactivity are currently a prime
area of research activity.2e5 In a recent study, we revealed that
reactions similar to that shown in Scheme 1 led to rather previously
unsuspected and unexpected products [e.g., 2 in Scheme 1b, after
the elimination of a molecule of CO2] by using functionalized
propargylic alcohols.6a Alkylidene substituted propargyl alcohols
led to another class of derivatives, the phosphono-indenes (e.g., 3,
Scheme 1c).6b
nucleophilicity of P(III) center in cyclodiphosph(III)azanes towards
alkenes, alkynes, allenylphosphonates, and azo compounds has
also been employed in isolating the products analogous to the
proposed intermediates in the well-known Mitsunobu reaction as
well as ‘umpolung addition’ via phosphine activation of alky-
nes.8c,10 In the reaction with allenylphosphonates, we have also
reported rather unusual ‘spontaneous resolution’ in which both the
enantiomers were separated by crystallization.11 The steric pro-
tection offered by the two ring N-t-Bu groups, amenability of the
system to be monitored by 31P NMR, and in most cases, good
crystallinity of the products makes these compounds as wonderful
precursors to probe organic reactions. Thus we wanted to explore
reactions with nitro-functionalized propargyl alcohols (cf.
Scheme 2) further in an effort to unravel the details of the new
reaction shown in Scheme 1b. The results include the structural
characterization of previously unsuspected class of products, and
unusual ways of forming phosphorus-free 2-substituted indoles,12
quinolinones, and tetrahydroacridine.
Cyclodiphosphazanes [XP(
m
-NR)2PY] (4) [R¼t-Bu or Ph] con-
stitute a well-known class of simple ring systems with two reactive
phosphorus(III) centers.7 In a significant number of their reactions,
the substitution reactions of the P-X/PeY bond and the oxidative
addition/coordinating ability of the phosphorus have been profit-
ably engaged to analyze ‘intermediates’ proposed in organic
2. Results and discussion
We shall first discuss the reaction of cyclophosphazane pre-
cursors 4aed (Chart 1) with propargyl alcohols. For generalization,
we then deal with the corresponding results using the P(III) pre-
cursors 5 and 6. Hydrolysis/thermal decarboxylation that leads to
phosphorus-free quinolinones, 2-substituted indoles, and
* Corresponding author. Tel.: þ91 40 2313 4856; fax: þ91 40 2301 2460; e-mail
addresses: kckssc@uohyd.ac.in, kckssc@yahoo.com (K.C. Kumara Swamy).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.064

2644
G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
t-Bu
H
OH
N
.
P
.
P
Toluene
.
Br
C
C
H
.
O
O
O
+
P
A
N
t-Bu
H
H
OH
70 oC, 8 h
- RNH2
R(H)N
N(H)R
B
Δ
Et3N,
O
O
R = t-Bu [4b, δ(P) 88.8]
i-Pr [4c, δ(P) 90.7]
(a)
P
Cl
7
-Et3N.HCl
t-Bu
N
Br
O
B
.
P
.
1 [δ(P) 6.5]
t-Bu
N
P
H
.
P
N
.
P
.
R(H)N
.
t-Bu
OH
N
t-Bu
B
A
R(H)N
O
A
NO2
R = t-Bu [8, δ(P) 9.2, 79.7; 78%]
i-Pr [9, δ(P) 9.4, 83.6; 55%]
O
O
(I)
(i) Et3N/THF
0-60 oC, 2 h
H
P
O
O
(b)
Scheme 3. Formation of allenes 8 and 9 from 4b,c.
P
Cl
O
(ii) Silica
-Et3N.HCl
N
H
-CO2
What is perhaps interesting is that, in the above reaction, if the
phenyl ring (A) has o-NO2 group, it produces the uncommon
cyclodiphosphazane based heterocycles. Thus treatment of [(t-
2 [δ(P) 16.1, quantitative, X-ray]
Me
Me
BuNH)P(m-N-t-Bu)]2 (4b) with the propargyl alcohol 10 leads to the
cyclodiphosphazanyl-indolinones 11 and 12,13. The yields of the
bis(cyclophosphazanyl) products 12,13 can be enhanced by in-
creasing the stoichiometry of the cyclophosphazane 4b (Scheme 4).
The yields given in Scheme 4 are from the isolation by column
chromatography. NMR (1H, 13C, and 31P), IR, and HRMS data confirm
the identity of 11.6a Additional proof comes from the single crystal
X-ray structural characterization of 12$1.5H2O and 13 [Figs. S1 and
S2, Supplementary data]. The difference in the structures of 12 and
13 stems from the trans or cis disposition of the P(O)/PNH(t-Bu)
groups on one of the cyclophosphazanyl residues, and conse-
quently, the intramolecular NH/O type H-bonding in 12. This
OH
Me
O
O
CO2Me
P
O
CO2Me
H
O
O
(c)
CO2Me
CO2Me
3 [δ(P) 17.5, 81%, X-ray]
P
Cl
Et3N/THF
0-60 oC, 6 h
Scheme 1. Reaction of P(III)eCl precursors with propargyl alcohols leading to (a) al-
lene 1, (b) benzepin 2, or (c) phosphono indene 3.
feature could have affected the d(C]O) in 12 in comparison to
compound 13. The reaction of isopropylamino substrate 4c with the
OH
same propargyl alcohol in 2:1 molar stoichiometry ratio mainly
-HX
+
P(III)
X
Products
R
NO2
OH
t-Bu
N
Scheme 2. Schematic representation of the reactions studied in this work.
.
P
.
P
Toluene
.
.
+
N
t-Bu
70 oC, 8 h
- RNH2
R(H)N
N(H)R
NO2
R = t-Bu (4b)
i-Pr (4c)
10
t-Bu
.
P
.
.
N
X , Y = Cl
NH-t-Bu
NH-i-Pr
(4a)
(4b)
(4c)
.
O
O
P
P
Cl Ph2 P Cl
N
t-Bu
Y
X
t-Bu
X = Cl, Y = NH-t-Bu (4d)
5
6
γ
O
N
α
.
P
N
OH
O
.
P
H
P
β
β
γ
Chart 1.
α
N
R(H)N
O
+
t-Bu
t-Bu
N
t-Bu
N
.
P
.
O2N
tetrahydroacridine is also described as appropriate. Mechanistic
features are briefly discussed at the end.
t-Bu(H)N
(II)
11
2.1. Reactivity of [(RNH)P(
m-N-t-Bu)]2 [R[t-Bu (4b), i-Pr (4c)]
γ
α
O
N
γ
O
and [(t-BuNH)P( -N-t-Bu)2PeCl] (4d) with functionalized
m
α
O
N
P
β
O
P
+
P
β
propargyl alcohols
P
O
t-Bu t-Bu
N
N
t-Bu
N
O
t-Bu
N
t-Bu t-Bu
N
N
t-Bu
N
t-Bu
N
Initially, we started the reaction of cyclodiphosphazanes 4b,c8c,d
with aryl substituted propargyl alcohol13 7 that led to cyclo-
diphosphazane based allenes 8 and 914 (Scheme 3). These are
formed by the attack of OH of the propargyl alcohol on cyclo-
diphosphazane followed by rearrangement. The 31P NMR shows
two signals, one at tetracoordinate region and the other at tri-
coordinate region, as expected. The presence of the allenic group is
H
.
P
.
.
P
.
.
P
N
R
.
.
P
.
R(H)N
N(H)R
R(H)N
R = t-Bu [12, X-ray]
i-Pr [14]
[13, X-ray]
Yields of isolated products 11-14 (see text for details)
12+13 (18%) [+ other products]
11 (34%)
Stoichiometry used (4b: 10): 1.2:1
Stoichiometry used (4b: 10): 2:1
Stoichiometry used (4c: 10): 2:1
readily inferred from IR [1912e1929 cmꢀ1] and 13C NMR [
d
(C]C]
12 (36%)
13 (28%)
11 (<15%)
C)w216] spectra. The PeC carbon appears at
d 107.5e107.7
14 (33%) [+ other hydrolyzed products]
[1J(PeC)w138e139 Hz]. It may be noted that a simple substitution
would lead to the product of type I.
Scheme 4. Formation of N-hydroxyindolinone 11 and indolinones 12e14 from 4b,c.

G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
2645
afforded bis(cyclophosphazanyl)indolinone 14, a compound with
a structure similar to 12. This assignment is based on the similarity
in the 1H NMR spectra between the two compounds. We did not
isolate any mono(cyclophosphazanyl) product that is similar to
compound 11. This observation may be related to higher reactivity
of the precursor 4c.
in 15 comprises the atoms N4, C13, C18, C19, C20, C21, and O2. A
careful perusal of the structure reveals that the position of the
carbon atoms at the C^C site of 10 has been altered. While there
are three intervening carbon atoms between the two-aryl groups in
the precursor 10, only two intervening carbon atoms are present in
the product 15.
Notable features in the structures of 11e14 are (i) the unusual
change of position of the b-carbon in the intermediate II and the final
products 11e14 suggesting a new rearrangement, (ii) the transfer of
an oxygen atom from the eNO2 group to a carbon in the five-
membered ring, and (iii) a rearrangement from P(III)eOeN to (O)
P(V)eN15 (for 12e14).
Use of the propargyl alcohol Me3SiC^CCH(OH)(2-NO2C6H4)
(18),13b which has a eSiMe3 group in place of a phenyl group in
PhC^CCH(OH)(2-NO2C6H4) (10) resulted in the formation of
cyclophosphazanyl-indolinones 19,20. Either of the two substrates
4b or 4d can be used in this reaction (Scheme 6). The molar stoi-
chiometry used was w1.2:1 [4b or 4d:18]. The production of 20 is
most likely caused by the hydrolysis on the silica gel column. The
structure of 19 is proven by X-ray crystallography [Fig. S5, Sup-
plementary data]. The principal difference in structure between
these two compounds (19,20) and 16 lies in the relative disposition
of phosphorus and the newly formed indolinone ring, as revealed
by the X-ray structure. While in 16, the phosphorus and C]O are cis
with respect to the intervening double bond, they are trans in 19
and 20. Steric factors involving the eSiMe3 (or Ph) group may be
responsible for this difference.
Surprised by the intricacies involved in the above reaction, we
probed the reaction further by using the monochloro-
cyclodiphosphazane 4d.8a It may be noted that a simple re-
placement of eCl by the propargyloxy group followed by rear-
rangement should have afforded the same compounds 12,13.
However, 12,13 were only the minor products and the major
products were the unsuspected and unusual phosphazane con-
nected cyclic products 15 and 16 (Scheme 5). The molar stoichi-
ometry used was 1.2:1 [4d:10]. Compound 15 is fairly stable but in
CDCl3 solution exhibits two sets of signals [ca. 7:3 ratio] in both 1H
and 31P NMR spectra, suggesting an isomerization process [cis5-
trans of P(O) and P(NH-t-Bu) groups]. It was not possible to dis-
tinguish these two isomers by TLC, but fortunately we could obtain
the crystal structure of one isomer of 15. This crystal also exhibited
isomerization in solution [CDCl3; 31P/1H NMR]. The 31P NMR
t-Bu
t-Bu(H)
N
O
N
.
P
P
γ
.
N
t-Bu
NH
α
β
4b
Me3Si
O
spectrum shows major signals at
d 73.1 and 3.0. It is interesting to
Toluene
OH
19 [X-ray, 42%]
80 oC, 6 h
note that we were able to isolate 2-phenyl-indole 17 (ca. 48%) from
the hydrolysis/dephosphorylation of compound 15. The reaction is
significant because a new (perhaps bizarre) route to 2-substituted
indoles has been uncovered.
or
+
SiMe3
NO2
O
t-Bu(H)
t-Bu(H)
N
N
4d
P
18
γ
THF, Et3N
80 oC, 8 h
- Et3N.HCl
α
NH
0
β
H
OH
t-Bu
O
N
.
P
.
P
THF, Et3N
20 [30%]
.
.
+
N
t-Bu
4d
70 oC, 12 h
Scheme 6. Formation of phosphorus-based indolinones 19 and 20.
0
Cl
t-Bu(H)N
NO2
10
- Et3N.HCl
Keeping the eNO2 group intact, subtle changes in the precursor
propargyl alcohol do bring in another novel species. Thus, by
replacing the phenyl group in 10 with a cyclohexenyl moiety in the
precursor 21, the fused polycycles 22,23 with a cyclopropane ring
can be readily isolated (Scheme 7). The 31P NMR spectra of 22,23
γ
α
β
N
O
γ
α
P
P
O
O
NH
β
O
N
+
P
Nt-Bu
t-Bu N
O
t-Bu(H)
N(H)t-Bu
.
.
15 (X-ray, 56%)
16 (X-ray, 32%)
OH
t-Bu
N(H)t-Bu
N
.
P
.
Toluene
.
.
Toluene/water (9:1)
110 oC/ 10 h
P
+
N
70 oC, 8 h
- RNH2
R(H)N
N(H)R
t-Bu
NO2
R = t-Bu (4b)
i-Pr (4c)
21
Ph
17 (see text)
N
H
t-Bu
t-Bu
O
N
O
.
N
.
.
.
P
P
H
O
P
P
α
γ
β
Scheme 5. Formation of oxa-aza-benzocycloheptenone 15, indolinone 16 and 2-
phenyl-indole from 4d.
α
N
N
R(H)N
t-Bu
R(H)N
β
t-Bu
γ
O
O2N
N
H
Compound 16 (cf. Scheme 5) was isolated in 32% yield. The 31P
NMR spectrum exhibited a single peak at d(P) 11.1, suggesting the
(III)
R = t-Bu [22, 84%. X-ray]
i-Pr [23, 62%]
cleavage of cyclodiphosphazane ring. The presence of PeC bond is
confirmed by a doublet at
d
154.2 [1J(PeC)¼126.0 Hz] in the 13C
Toluene + H2O (9:1)
110 oC, 8 h
NMR spectrum. A carbonyl resonance at 168.7 is also clearly dis-
cernible in the spectrum. All these data are consistent with the
structures shown in Scheme 5. Further confirmation of the struc-
tures 15 and 16 is provided by single crystal X-ray structures [Figs.
S3 and S4, Supplementary data]. The novel seven-membered ring
22
N
24 (36%)
(+ other products)
Scheme 7. Formation of fused polycycles 22,23 from 4b,c and propargyl alcohol 21.

2646
G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
show two signals each at
d
74.3, 10.3 and 78.9, 10.2, respectively;
that we could obtain the phosphorus-free indole 17 or 32 starting
from 28 or 30, respectively.
In the reactions using Ph2PCl (6) shown in Scheme 9, products 35
and 37 are similar to 19. Compounds 38, 40 (X-ray, see Figs. 1, 2 and
these values are close to that for 8 and 9. However, in the 13C NMR
spectra, the PeC carbon appears at
d
w38 [1J(PeC)w140e143 Hz]
and (C]O) around 171, which are quite different from that of the
d
phosphoramidyl-allenes 8 and 9. Fortunately, we were successful in
obtaining the X-ray crystal structure of 22 that shows the novel
structure. The three membered rings comprise [C13, C16, C21] and
[C40, C43, C48] atoms in the two molecules present in the asym-
metric unit. The nitrogen [N4/N8] from the precursor is part of
a six-membered ring with both the oxygen atoms of the nitro group
transferred to a carbon [Fig. S6, Supplementary data]. Based on the
reaction shown in Scheme 1, compounds 22 and 23 are likely to be
formed via cyclodiphosphazane based allene intermediate (III) that
further undergoes cyclization using the eNO2 functionality. Treat-
ment of the same propargyl alcohol 21 with the cyclo-
diphosphazane 4d in the presence of Et3N also led to the product
22. Interestingly, compound 22 could be dephosphonylated to
tetrahydroacridine 24 (NMR and HRMS evidence16) and other
products in the presence of water.
OH
R2
THF/Et3N
+
Ph2PCl
R1
70 oC, 8 h
NO2
10, 25, 33 or 34
6
-CO2
R2
R2
R1
R2
Ph2P(O)
R1
+
+
O
N
NH
N
O
R1
R1 = Ph, R2 = H
P(O)Ph2
36 (52%)
P(O)Ph2
O
35 (30%)
R1 = n-C5H11, R2 = H 37 (26%)
not isolated
38 (20%)
39 (28%)
R1 = n-C5H11, R2 = Cl not isolated
R1 = n-C5H11, R2 = Br not isolated
40 (62%, X-ray)
41 (26%)
see text
42 (62%)
2.2. Reactions of propargylic alcohol with the P(III) pre-
cursors (OCH2CMe2CH2O)PCl (5) and Ph2PCl (6)
Toluene + H2O
(9:1)
110 oC, 8 h
Basic alumina
EtOAc
As an extension to the above studies, we wanted to explore
similar reactions by using other P(III) precursors like 5 and 6. In the
reaction shown in Scheme 8, while the product 26 (X-ray, Fig. S7) is
similar to 12e14 obtained by using the cyclodiphosphazanes 4b,c,
the second product 27 isolated after column chromatography is the
PeN bond cleaved product from 26 and is analogous to 16. Using
the propargyl alcohol 25, we could isolate analogous product 29 (X-
ray, Fig. S8). Although we did not isolate the product 28 in our
earlier attempts, we could do so after isolating 3017 (and realizing
that we missed it). The product 31 from the silyl substituted
propargyl alcohol 18 is close in structure to compound 20. The
assignment of trans-stereochemistry to 31 is based on a NOESY
experiment. However, the more important result of this part was
rt, 15 h
H
N
O
R2
R1
R2
R1
N
H
(+ others, see text)
R1 = Ph, R2 = H
(17, 88%)
= n-C5H11, R2 = H (32, 87%)
= n-C5H11, R2 = Cl (46, 92%)
= n-C5H11, R2 = Br (47, 93%)
R1 = n-C5H11, R2 = H (43, 59%, X-ray)
= n-C5H11, R2 = Cl (44, 68%)
= n-C5H11, R2 = Br (45, 64%)
Scheme 9. Formation of phosphinoyl indolinones/indoles/oxa-aza-benzocycloheptenones
[35e42] and phosphorus-free quinolinones/indoles [17, 32, 43e47].
OH
THF/Et3N
70 oC, 8 h
O
O
+
P
Cl
R
NO2
(10)
5
R = Ph
n-C5H11 (25)
P
R
P
R
R
+
+
N
N
P
P
NH
O
O
R = Ph
n-C5H11
26 (31%, X-ray) 27 (40%)
29 (40%, X-ray)
28 (12%)
30 (33%)
-
Basic alumina
EtOAc
RT, 15 h
Similarly
P
R
N
NH
H
H
R = Ph
(17, 90%)
O
n-C5H11 (32, 84%)
31 [ 61%, using 5 and 18]
O
O
O
P
P
Fig. 1. (a) Compound 38, (b) compound 38 upon melting and keeping the temperature
at 120 ꢁC for 2 h converted to 39, and (c) TGA of compound 38 showing weight loss
corresponding to the elimination of CO2 to lead to 39.
Scheme 8. Formation of fused phosphono-indolinones/indoles 26e31 and
phosphorus-free indoles 17 and 32.

G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
2647
O
t-Bu
N
N
OH
O
N
O
N
t-Bu
O
P
N
P
.
P
.
P
O
.
.
O
N
t-Bu
0 o
C
60 oC
N
t-Bu
Cl
Cl
O
O
4a
Et3N/ THF/ 10 h
[48, δ(P): -17.3, 74%, X-ray]
Scheme 10. Reaction of N-hydroxy succinimide with 4a leading to PeN substituted
product 48.
initially showed substantial amounts of a partially (one side) rear-
ranged product [
d
(P): 124.6, ꢀ9.1, 2J(PP)¼12.0 Hz] vindicating our
assertion that rearrangement takes place after substitution. At the
end, compound 48 (X-ray, Fig. S11) is the major product, but the
other isomer is also present in minor quantities (<15%).
Fig. 2. ORTEP of compound 40 (hydrogen atoms are omitted for clarity).
S9) and 41 are similar to 15. Analogous compounds with R1¼Ph and
R2¼H could not be isolated because of the facile decarboxylation to
36. Elimination of CO2 from 38, 40, and 41 leads to N-substituted
indoles 36, 39, and 42, respectively, during chromatography or upon
melting. In the case of R1¼n-C5H11 and R2¼Cl, we could isolate
2.4. Mechanistic pathways
As discussed above in Scheme 3 (compounds 8 and 9), the
normal reaction of a propargyl alcohol with cyclodiphosphazane
(or
a
P(III)eCl precursor) is expected to lead to the
a similar species [d(P) 26.6 and HRMS: calcd for C25H25ClNOP
(MþþH and MþþHþ2) 422.1441 and 424.1441; found 422.1440 and
424.1413] only in 95% purity. The elimination of CO2 was established
in the case of 38 by recording the 31P NMR spectra before and after
melting (with bubbling) and also by recording TGA (Fig. 1).
Compounds 38, 40, and 41 could be readily dephosphonylated
to the quinolinones 43e45 by treating them with toluene/water
mixture (cf. Scheme 9 above). Although indoles of the type 39/42
(ca. 15%) were also present alongside, we could easily isolate qui-
nolinones 43e45. We could get the single crystal X-ray structure of
one of these (43; Fig. 3 and S10) to confirm their identity.18 We are
rather puzzled by this observation because in these cases there is
elimination of oxygen in addition to the removal of phosphonate
group. Formation of phosphorus-free indoles 17, 32, 46, and 47
occurs via base hydrolysis. The reaction, as mentioned above, offers
a new way to generate 2-substituted indoles.
cyclophosphazanyl-allenic intermediate IV (Scheme 11). The
b
-
carbon (relative to the phosphorus) in IV is the
g-carbon in the
structures of 11e14, 16, and 19,20.19 This observation needs an
explanation. Since in most cases, the nucleophilic attack takes place
at the
attacks the
b
-carbon of the allene,20 the oxygen end of the eNO2 group
b
-carbon to lead to the cyclic zwitterionic intermediate
V, facilitated by the phosphoryl group. In the next step, rear-
rangement leads to species (VI). Formation of the five-membered
ring can then be envisioned to lead to the cyclophosphazanyl-N-
Fig. 3. ORTEP of compound 43. There are two dimers present in the asymmetric unit,
one set is shown here. Hydrogen atoms (except NH) are omitted for clarity.
2.3. Reactivity of 4a towards N-hydroxy-succinimide
In the reaction leading to compounds 12e14 shown in Scheme
4, it can be inferred that the reaction of the eOH group of the N-
hydroxy moiety in 11 with an additional cyclodiphosphazane
molecule must have led to the PeN bonded compounds 12e14. To
our knowledge, such reactions have never been reported in cyclo-
diphosphazane chemistry and in order to conclusively establish
that products 12e14 result from such a reaction, we treated
cyclodiphosphazane 4a with N-hydroxy-succinimide. This reaction
afforded the novel rearranged product 48 (Scheme 10). It is formed
by the substitution of a chloro group by the N-hydroxyl reactant,
followed by PeOeN to P(O)N rearrangement. The reaction mixture
Scheme 11. Possible pathways for the formation of the new N-heterocycles presented
in this work [cf. Schemes 3e9].

2648
G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
hydroxy product 11. The stereochemistry at the newly formed
double bond may be a result of steric factors involving the R0 group.
Compounds 12e14 result from the further reaction of this in-
termediate 11 with the respective cyclodiphosphazane (Scheme
11a) that also involves P(III)eOeN to P(V)(O)eN rearrangement.
Proof for the latter rearrangement has been provided in this work
by the structural characterization of 48. Hydrolysis of such a species
by adventitious moisture (or during the column chromatography)
may then lead to facile formation of cyclophosphazanyl-indolinone
(19) or the ring-opened products 16/20. Formation of the fused
heterocycles 22 and 23 may also be rationalized by appropriate
bond-movements from VI (R0¼1-cyclohexenyl; Scheme 11b). The
breaking of NeO bond from the intermediate VII would lead to the
products 22 and 23.21 Formation of 24 from 22 requires elimination
of two molecules of CO in addition to the phosphorus moiety. The
seven-membered ring compound 15 looks odd, but we presume
that intermediate (VII0; Scheme 11c) may again be involved. At the
moment we need to admit that the suggested pathway is still
speculative. The isolation of the analogous compounds 38, 40, and
41 and thermal conversion of 38 to the 2-substituted indole 39 by
elimination of CO2 (cf. Scheme 9 above) also suggests an alternative
pathway for these reactions. The substituted indoles 36, 39, and 42
are formed in a similar manner. Finally, the electronic effect in-
duced by the P(V) center due to the shrinking of the P(V)eN(ring)
bond may be responsible for the observation that only one end of
the cyclodiphosphazane is reactive.
spectra were recorded using LC/MS and HRMS (ESI-TOF analyzer)
equipment.
Cyclodiphosphazane precursors [ClP(m
-N-t-Bu)]2,23 (4a), [(RNH)
P(m
-N-t-Bu)]2 [R¼t-Bu (4b),8c i-Pr (4c),8d [(t-BuNH)P(
m-N-t-Bu)2PCl]
(4d),8a and propargyl alcohols13 7, 10, 18, 21, 25, 33, and 34 were
prepared by known synthetic routes.
4.2. Synthesis of cyclodiphosphazane based allenes 8,9 and
enamine 9a
4.2.1. [(t-BuNH)P(
m-N-t-Bu)2P(]O)eC(Ph)]C]CH(Ph)]
8. In
a round bottomed flask (RBF), [(t-BuNH)P(
m-N-t-Bu)]2 (4b) (0.365 g,
1.05 mmol), and propargyl alcohol 7 (0.218 g, 1.05 mmol) were
dissolved in dry toluene (6 mL), and the mixture was heated with
stirring at 70 ꢁC for 8 h. After the completion of the reaction (TLC),
solvent was removed under reduced pressure. The crude product
was purified by column chromatography (hexane/EtOAc) affording
8 as a white crystalline solid. Yield 0.395 g (78%); mp 174e178 ꢁC; Rf
(30% EtOAc/hexane) 0.55; nmax (KBr) 3441, 3252, 3059, 2967, 2866,
1929, 1597, 1495, 1458, 1364, 1221, 1138, 1076, 1034, 1001, 932, 907,
882, 816 cmꢀ1
; dH (400 MHz, CDCl3) 7.60e7.22 (m, 10H), 6.66 (d,
J¼11.2 Hz, 1H), 3.30 (d, J¼7.2 Hz, 1H), 1.34, 1.31 (2s, 27H); dC
(100 MHz, CDCl3) 216.2, 134.43, 134.35, 132.83, 132.76, 128.7, 128.5,
127.8, 127.50, 127.46, 107.7 (d, J¼138.0 Hz), 96.7 (d, J¼13.0 Hz), 52.8
(d, J¼4.0 Hz), 52.0 (d, J¼14.0 Hz), 32.8 (d, J¼9.0 Hz), 31.4 (d,
J¼5.0 Hz); 31P NMR (162 MHz, CDCl3) 79.73 (d, J¼11.0 Hz), 9.21 (d,
J¼11.0 Hz); HRMS (ESI): [MþþH], found 484.2646. C27H39N3OP2
requires 484.2647.
3. Conclusions
We have presented several new and previously unpredicted
outcomes in the reactions of the cyclodiphosphazanes with func-
4.2.2. [(i-PrNH)P(
by-product
m
-N-t-Bu)2P(]O)eC(Ph)]C]CH(Ph)] 9 and the
[(i-PrNH)P( -N-t-Bu)2P(]O)eC(Ph)]C(NH(i-Pr)e
m
tionalized propargyl alcohols.
A
set of indolinones and 2-
CH2Ph] 9a. The procedure was similar to that for compound 8 using
cyclodiphosphazane [(i-PrNH)P( -N-t-Bu]2 (4c) [ (P) 90.7; 0.509 g,
substituted indoles were also prepared from the reaction of the
precursors (OCH2CMe2CH2)PCl (5) and Ph2PCl (6) with nitro-
functionalized propargyl alcohols. The main advantage of the
cyclodiphosphazane substrates 4aed, apart from their ready ac-
cessibility and use as 31P NMR probes, is that the products tend to
be crystalline solids readily amenable for structure determination
thus assisting us to delineate intricate pathways in these apparently
simple reactions. For example, it is known that in the activity of
several high-energy materials (e.g., TNT) the oxygen of the eNO2
group ultimately leaves as CO2, but the detailed reaction chemistry
is not obvious. Looking at the structures, such as 15 or 22e23, we
could perhaps get an idea of the involvement of unusual in-
termediates. We have also examined ways by which the current
reaction may be put to practical use, for example, by complete re-
moval of phosphorus-moiety. This has led to the isolation
phosphorus-free indoles [17, 32, 46 and 47], tetrahydroacridine [24]
and quinolinones [43e45]. Thus the present work illustrates new
ways of generating such heterocycles.
m
d
1.59 mmol] and propargyl alcohol 7 (0.33 g, 1.59 mmol). The re-
action time was 8 h. The eluent for column chromatography was
hexane/EtOAc. Compound 9a as a minor product was also isolated
subsequently (see later for characterization data) along with com-
pound 9. Yield 0.413 g (55%); mp 154e156 ꢁC; Rf (30% EtOAc/hex-
ane) 0.32; nmax (KBr) 3244, 2959, 2920, 2871,1912,1594,1490,1452,
1414, 1359, 1260, 1233, 1216, 1134, 1074, 926, 888, 816 cmꢀ1
; dH
(400 MHz, CDCl3) 7.60e7.21 (m, 10H), 6.66 (d, J¼11.6 Hz, 1H), 3.55
(br, 1H), 3.02 (br, 1H), 1.33, 1.30 (2s, 18H), 1.20 (d, J¼6.4 Hz, 6H); dC
(100 MHz, CDCl3) 216.1, 134.4, 134.3, 132.8, 132.7, 128.8, 128.6, 127.9,
127.6, 107.5 (d, J¼139.0 Hz), 96.9 (d, J¼13.0 Hz), 52.8 (d, J¼5.0 Hz),
45.1 (d, J¼29.0 Hz), 31.3, 26.5; 31P NMR (162 MHz, CDCl3) 83.64,
9.42; HRMS (ESI): [MþþH], found 470.2491. C26H37N3OP2 requires
470.2491.
Compound 9a was also isolated along with 9. Yield 0.286 g
(34%); mp 102e104 ꢁC; Rf (30% EtOAc/hexane) 0.64; nmax (KBr)
3375, 3216, 3117, 2970, 2920, 2865, 1605, 1590, 1495, 1462, 1414,
1358, 1342, 1212, 1188, 1112, 1069, 1035, 973, 939, 889 cmꢀ1
; dH
4. Experimental section
4.1. General
(400 MHz, CDCl3) 9.06 (d, J¼9.2 Hz, 1H), 7.30e7.05 (m, 10H), 3.60
(1s, 2H), 3.51e3.33 (br, 2H), 2.79 (t, 1H), 1.24 (s, 18H), 1.15 (d,
J¼6.4 Hz, 6H), 1.07 (d, J¼6.4 Hz, 6H); dC (100 MHz, CDCl3)
158.3 (d, J¼12.0 Hz), 139.7, 139.6, 139.2, 130.6, 128.4, 127.7, 127.6,
125.9, 125.3, 94.4 (d, J¼146.0 Hz), 52.2 (d, J¼5.0 Hz), 44.7 (d,
J¼31.0 Hz), 44.5, 36.1 (d, J¼13.0 Hz), 31.0 (t), 26.5 (d, J¼4.0 Hz),
24.7; 31P NMR (162 MHz, CDCl3) 85.54 (PeNHi-Pr), 28.77 (PeC);
HRMS (ESI): [MþþH], found 529.3222. C29H46N4OP2 requires
529.3226.
All synthesis and manipulations were performed under nitrogen
atmosphere unless stated otherwise. Chemicals/solvents were pu-
rified as required using standard procedures,22 unless otherwise
noted. 1H, 13C, and 31P NMR spectra (1H 400 MHz, 13C 100 MHz, and
31P 162 MHz) were recorded using a CDCl3 solution (unless stated
otherwise) with shifts referenced to SiMe4
(
d
¼0) or 85% H3PO4
(d
¼0). Melting points were determined by using a hot stage melting
4.3. Synthesis of cyclophosphazane containing and phos-
phorus free N-heterocycles [11e17], [19,20], [22e24]
point apparatus and were uncorrected. IR spectra were recorded on
an FT-IR spectrophotometer. Elemental analyses were carried out
on a PerkineElmer 240C CHN or Thermo-Finnigan EA1112 CHNS
analyzer from School of Chemistry, University of Hyderabad. Mass
4.3.1. [(t-BuNH)P(
m-N-t-Bu)2P(O)eC(Ph)]C{eC6H4eN(OH)eC(]
O)e}] 11. The procedure was similar to that for compound 8 using

G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
2649
[(t-BuNH)P(
m
-N-t-Bu)]2 (4b) [0.73 g, 2.1 mmol] and propargyl al-
NMR (162 MHz, CDCl3) 89.10, 85.45, 6.84, ꢀ4.20; HRMS (ESI):
[MþþH], found 776.3865. C37H61N7O3P4 requires 776.3865.
cohol 10 (0.44 g, 1.74 mmol). The reaction was conducted at 70 ꢁC
for 8 h. Eluent for column chromatography was hexane/EtOAc
(1:2). Yellow solid; yield (after isolation) 0.316 g (34%); mp
226e228 ꢁC; Rf (70% EtOAc/hexane) 0.33; nmax (KBr) 3470, 3289,
3138, 3081, 3029, 2967, 1705, 1699, 1616, 1557, 1466, 1362, 1325,
4.3.4. (t-BuNH)P(m-N-t-Bu)2P(O)N[eoeC6H4eC(H)]C(Ph)eC(O)e
Oe] 15, [(t-BuNH)2P(O)eC(Ph)]C{eC6H4eNHeC(]O)e}] 16, and
the indole 17. An oven dried 25 mL round-bottomed flask was
charged with propargyl alcohol 10 (0.25 g, 0.99 mmol), NEt3
(0.17 mL, 1.18 mmol), and dry THF (5 mL). The mixture was stirred
1213, 1082, 1032, 997, 889, 831 cmꢀ1
; dH (400 MHz, CDCl3) 8.80 (s,
1H), 7.47e7.32 (m, 5H), 7.09 (dd, 1H), 6.88 (d, J¼7.6 Hz, 1H), 6.55
(dd, 1H), 5.45 (d, J¼8.0 Hz, 1H), 3.62 (d, J¼2.4 Hz), 1.38, 1.37 (2s,
27H); dC (100 MHz, CDCl3) 166.8, 152.9 (d, J¼121.0 Hz), 142.6, 141.5,
135.9, 130.4, 128.9, 128.8, 128.2, 126.0, 123.9, 123.8, 121.6, 109.8,
52.5 (d, J¼7.0 Hz), 52.0 (d, J¼15.0 Hz), 33.0 (d, J¼9.0 Hz), 31.8; 31P
NMR (162 MHz, CDCl3) 81.92 (d, J¼12.0 Hz), 6.23 (d, J¼12.0 Hz);
HRMS (ESI): [MþþH], found 529.2499. C27H38N4O3P2 requires
529.2498.
at 0 ꢁC for 5 min. To this, [(t-BuNH)P(
m
-N-t-Bu)2PeCl] (4d) (0.369 g,
1.18 mmol) dissolved in dry THF (5 mL) was added drop-wise at
ꢁC over a period of 15 min, and then the mixture allowed to
0
warm to rt followed by heating at 70 ꢁC for 12 h with continuous
stirring. Filtration followed by removal of the solvent and purifi-
cation by column chromatography (hexane/acetone; 9:1) afforded
product 15 followed by 16. Although we could get an X-ray
structure of the major product 15 (crystallization from ethyl ace-
tateþchloroform), this compound underwent degradation/isom-
erization in solution and hence spectra for the pure isomer could
not be obtained.
4.3.2. [(t-BuNH)P(
P(O)( -N-t-Bu)2P(t-BuNH)] 12 and 13. The procedure was the same
as that for 8, using [(t-BuNH)P( -N-t-Bu)]2 (4b) (0.80 g, 2.29 mmol)
m-N-t-Bu)2P(O){eNeC6H4eC(C]O)]C(Ph)e}e
m
m
and propargyl alcohol 10 (0.29 g, 1.15 mmol); reaction time was 8 h
and the eluent for column chromatography was hexane/EtOAc
(1:1). Compound 12 was eluted firstly and followed by isomer 13.
Compound 12. Yellow solid; yield 0.333 g (36%); mp 214e216 ꢁC;
Rf (50% EtOAc/hexane) 0.5; nmax (KBr) 3501, 3316, 3212, 2971, 1728,
Compound 15. Pale yellow solid; yield 0.292 g (56%); mp
164e166 ꢁC; Rf (10% acetone/hexane) 0.5; nmax (KBr) 3424, 2970,
2931, 2854, 1731, 1462, 1369, 1276, 1216, 1084, 1040, 958, 887 cmꢀ1
;
dH (400 MHz, CDCl3) 8.10e7.27 (m, 10H), 3.07 (d, J¼6.4 Hz, 1H), 1.34,
1.33, 1.24 (3s, 27H), additional peaks at 8.07e7.25, 3.42 (d), 1.56,
d
1638, 1595, 1458, 1364, 1308, 1211, 1082, 1034, 961, 885 cmꢀ1
;
dH
1.54, 0.95 were also seen; dC (100 MHz, CDCl3) 171.4, 142.0, 138.3,
(400 MHz, CDCl3) 8.37 (d, J¼8.4 Hz, 1H), 7.45 (m, 3H), 7.30 (m, 2H),
7.13 (wdd, 1H), 6.59 (wdd, 1H), 5.44 (d, J¼8.0 Hz, 1H), 5.40 (d,
J¼7.6 Hz, 1H), 3.68 (s, 1H), 1.46, 1.38, 1.36, 1.32 (4s, 54H); dC
(100 MHz, CDCl3) 166.2, 151.2 (d, J¼121.8 Hz), 144.1, 141.9, 141.8,
136.4, 130.9, 129.1, 129.0, 128.9, 128.2, 125.5, 124.3, 124.2, 122.7,
116.2, 53.2 (d, J¼9.0 Hz), 52.6 (d, J¼6.0 Hz), 51.9, 51.8, 33.2 (d,
J¼7.5 Hz), 32.6 (d, J¼3.6 Hz), 32.0 (d, J¼4.3 Hz), 31.1 (d, J¼4.3 Hz),
29.8; 31P NMR (162 MHz, CDCl3) 85.22 (d, J¼14.0 Hz), 85.06, 9.06 (d,
J¼14.0 Hz), ꢀ5.18; HRMS (ESI): [MþþNa], found 826.3989.
135.5, 133.0, 132.8, 130.8, 130.2, 128.9, 128.6, 128.3, 127.7, 126.8,
125.3, 53.2, 52.0, 32.9, 31.8, 31.1 additional peaks at
d 172.3, 141.1,
138.3, 136.5, 135.1, 133.0, 132.1, 130.8, 129.0, 128.3, 127.5, 121.8, 52.2,
52.0, 32.8, 31.7, 31.0 were also seen due to isomerization/trans-
formation; 31P NMR (162 MHz, CDCl3) 73.07 (d, J¼6.8 Hz), 3.01 (d,
J¼6.8 Hz) and peaks at
d
74.14 (d, J¼11.6 Hz), ꢀ0.66 (d, J¼11.6 Hz)
were also observed (for the other isomer in solution); HRMS (ESI):
[MþþNa], found 551.2317. C27H38N4O3P2 requires 551.2317.
Compound 16. Yellow solid; yield 0.129 g (32%); mp 230e234 ꢁC;
Rf (10% acetone/hexane) 0.27; nmax (KBr) 3351, 3065, 2965, 2816,
C
39H65N7O3P4 requires 826.3997. X-ray structure was determined
for this isomer.
1699,1616,1466, 1383,1331,1217,1011, 837, 748 cmꢀ1
; dH (400 MHz,
Compound 13. Yellow solid; yield 0.259
g
(28%); mp
CDCl3) 9.87 (s, 1H), 7.42e7.27 (m, 5H), 7.03 (dd, 1H), 6.65 (d,
J¼7.6 Hz, 1H), 6.55 (dd, 1H), 5.78 (d, J¼7.6 Hz, 1H), 4.09 (d, J¼7.2 Hz,
2H), 1.36 (s, 18H); dC (100 MHz, CDCl3): 168.7, 154.2 (d, J¼126.0 Hz),
142.3, 138.82, 138.8, 132.6, 132.5, 129.9, 128.8, 127.9, 125.0, 123.3,
123.2, 121.6, 110.3, 51.9, 32.3, 32.2; 31P NMR (162 MHz, CDCl3) 11.11;
HRMS (ESI): [MþþNa], found 434.1974. C23H30N3O2P requires
434.1974. X-ray structure was determined for this compound. Note:
When compound 15 (0.18 g) was heated with toluene/water (9:1)
mixture at 110 ꢁC/12 h, the indole derivative 17 could be isolated
(0.031 g, ca. 48%). Rf (10% EtOAc/hexane) 0.53. It is a known com-
pound.24 The 1H/13C NMR spectra were identical to that for the
commercially available (Aldrich) sample.
204e206 ꢁC; Rf (50% EtOAc/hexane) 0.46; nmax (KBr) 3410, 3246,
2967, 2926, 2855, 1699, 1632, 1547, 1464, 1385, 1366, 1312, 1269,
1221, 1146, 1080, 1038, 1009, 918, 893 cmꢀ1
; dH (400 MHz, CDCl3)
8.20 (d, J¼8.0 Hz, 1H), 7.42 (m, 3H), 7.28 (m, 2H), 7.13 (wdd, 1H),
6.57 (wdd, 1H), 5.50 (d, J¼7.6 Hz, 1H), 3.38 (br, 1H), 3.09 (d,
J¼3.6 Hz, 1H), 1.38, 1.36, 1.34, 1.32 (4s, 54H); dC (100 MHz, CDCl3)
166.2, 151.1 (d, J¼121.7 Hz), 144.1, 141.82, 141.81, 139.4, 136.4, 131.0,
129.0, 128.9, 128.2, 125.5, 124.3, 124.1, 123.7, 122.7, 116.2, 53.2 (d,
J¼9.1 Hz), 52.6 (d, J¼6.0 Hz), 51.8 (d, J¼15.4 Hz), 50.9, 33.2 (d,
J¼7.4 Hz), 32.6 (d, J¼8.0 Hz), 32.0, 31.8 (d, J¼4.3 Hz), 31.1, 29.8; 31
P
NMR (162 MHz, CDCl3) 83.8 (br), 73.42 (br), 6.31 (d, J¼11.0 Hz),
ꢀ5.73 (d, J¼6.5 Hz); HRMS (ESI): [MþþNa], found 826.3997.
C
39H65N7O3P4 requires 826.3997. X-ray structure was determined
4.3.5. [(t-BuNH)P(m-N-t-Bu)2P(O)eC(SiMe3)]C{eC6H4eNHeC(]
for this isomer also.
O)e}] 19 and [(t-BuNH)2P(O)eCH]C{eC6H4eNHeC(]O)e}]
20. The procedure was similar to that for compound 8 using [(t-
4.3.3. [(i-PrNH)P(
P(O)( -N-t-Bu)2P(i-PrNH)] 14. The procedure was similar to that for
compound 8 using [(i-PrNH)P( -N-t-Bu)]2 (4c) [ (P) 90.7; 1.33 g,
4.14 mmol] and propargyl alcohol 10 (0.52 g, 2.07 mmol). The re-
action was conducted at 70 ꢁC for 8 h and the eluent for column
chromatography was hexane/EtOAc (2:1). Yellow solid; yield
0.523 g (33%); mp 234e238 ꢁC; Rf (30% EtOAc/hexane) 0.54; nmax
(KBr) 3326, 2964, 2920, 1720, 1594, 1451, 1369, 1221, 1166, 1134,
m
-N-t-Bu)2P(O){eNeC6H4eC(C]O)]C(Ph)e}e
BuNH)P(m-N-t-Bu)]2 (4b) [0.56 g, 1.61 mmol] and propargyl alcohol
m
18 (0.34 g, 1.34 mmol). The reaction time was 6 h at 80 ꢁC and the
eluent was hexane/EtOAc (2:1) to obtain solids 19 (eluted first)
and 20.
m
d
Compound 19. Yellow solid; yield 0.289 g (42%); mp 242e246 ꢁC;
Rf (30% EtOAc/hexane) 0.58; nmax (KBr) 3431, 2965, 2856,1718,1609,
1459, 1371, 1247, 1205, 1071, 890, 843 cmꢀ1
; dH (400 MHz, CDCl3)
9.06 (d, J¼8.0 Hz, 1H), 7.76 (s, 1H), 7.23 (dd, 1H), 7.02 (dd, 1H), 6.76
(d, J¼7.2 Hz, 1H), 3.50 (d, J¼5.6 Hz, 1H), 1.40, 1.38 (2s, 27H), 0.43 (s,
9H); dC (100 MHz, CDCl3): 168.7 (d, 3J(PeC)¼31.0 Hz), 155.0 (d,
J¼90.0 Hz), 150.8, 143.7, 131.9, 131.4, 123.2, 122.2, 109.6, 52.9 (d,
J¼4.0 Hz), 52.4 (d, J¼15.0 Hz), 33.0 (d, J¼9.0 Hz), 31.54, 31.46 (d,
J¼10.0 Hz), 4.5; 31P NMR (162 MHz, CDCl3) 92.87 (d, J(PeP)¼
12.0 Hz), 24.50 (d, J¼12.0 Hz); HRMS (ESI): [MþþH], found
1073, 887, 805 cmꢀ1
;
dH (400 MHz, CDCl3) 8.34 (d, J¼8.4 Hz, 1H),
7.48e7.29 (m, 5H), 7.14 (wdd, 1H), 6.60 (wdd, 1H), 5.50 (m, 2H),
3.58 (br, 3H), 1.37, 1.35, 1.34, 1.32 1.23, 1.21 (6s, 48H); dC (100 MHz,
CDCl3) 166.3, 151.5 (d, J¼122.0 Hz), 144.08, 144.05, 141.7, 141.6, 136.0,
131.1, 129.1, 128.6, 128.2, 125.5, 124.1, 123.9, 122.8, 115.9, 53.2 (d,
J¼9.0 Hz), 52.5 (d, J¼6.0 Hz), 46.1, 45.7, 31.9, 31.0, 26.7, 26.5; 31P

2650
G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
509.2629. C24H42N4O2P2Si requires 509.2631. X-ray structure was
determined for this compound.
5.65; N, 2.71%].; Rf (40% EtOAc/hexane) 0.22; nmax (KBr) 2965, 1728,
1601, 1466, 1408, 1262, 1061, 1019, 799 cmꢀ1
dH (400 MHz, CDCl3)
;
Compound 20. Yellow solid; yield 0.136 g (30%); mp 118e120 ꢁC;
Rf (30% EtOAc/hexane) 0.38; nmax (KBr) 3265, 2970, 2926, 2876,
1718,1614,1528,1467,1391,1366,1293,1260,1221,1090,1046,1013,
8.56 (d, J¼8.0 Hz, 1H), 7.73 (d, J¼8.0 Hz, 1H), 7.45e7.27 (m, 6H), 7.17
(t, 1H), 4.31e3.52 (m, 8H), 1.36, 1.24, 0.83, 0.74 (4s, 12H); dC
(100 MHz, CDCl3) 167.8 (d, J¼26.0 Hz), 141.8, 138.9 (d, J¼167.0 Hz),
136.1, 135.6, 135.5, 132.5, 128.5, 128.33, 128.26, 128.2, 127.6, 124.0,
121.4, 121.3, 114.0, 79.4 (d, J¼7.0 Hz), 77.3 (d, J¼7.0 Hz), 32.4 (dd,
J¼7.0 Hz), 22.5, 22.0, 20.8, 20.4; 31P NMR (162 MHz, CDCl3) 3.47,
ꢀ14.69; LC/MS m/z 518 [Mþ1]þ.
920, 838 cmꢀ1
;
dH (400 MHz, CDCl3) 8.81 (d, J¼8.0 Hz, 1H), 8.16 (s,
1H), 7.25e6.81 (m, 3H), 6.82 (d, J¼12.8 Hz, 1H), 2.55 (d, J¼9.2 Hz,
2H), 1.35 (s, 18H); dC (100 MHz, CDCl3) 169.0 (d, J¼22.0 Hz), 142.6,
137.64, 137.59, 131.4, 130.4 (d, J¼147.0 Hz), 129.5, 123.0, 121.1, 121.0,
109.8, 52.0, 32.1; 31P NMR (162 MHz, CDCl3) 9.32; HRMS (ESI):
[MþþH], found 336.1840. C17H26N3O2P requires 336.1842.
Compound 27. Yellow solid; yield 0.35 g (40%); mp 172e174 ꢁC; Rf
(40% EtOAc/hexane) 0.44; nmax (KBr) 3238, 2981, 2964, 2926, 1726,
1622, 1468, 1392, 1337, 1227, 1200, 1052, 1014, 986, 953 cmꢀ1
; dH
4.3.6. [(t-BuNH)P(
m
-N-t-Bu)2P(O){C15H14NO2}] 22. Compound 4b
(400 MHz, CDCl3) 8.47 (d, J¼8.0 Hz, 1H), 8.17 (s, 1H), 7.42e7.23 (m,
6H), 7.02 (t, 1H), 6.65 (d, J¼7.6 Hz, 1H), 3.90e3.56 (m, 4H), 1.21 (s,
3H), 0.74 (s, 3H); dC (100 MHz, CDCl3) 167.0 (d, J¼25.0 Hz), 142.5,
137.9 (d, J¼159.0 Hz), 137.0, 136.2, 136.1, 131.9, 128.4, 128.33, 128.27,
128.2, 128.0, 122.4, 120.5, 120.4, 109.7, 77.1 (d, J¼7.0 Hz), 32.4 (d,
J¼7.0 Hz), 22.0, 20.9; 31P NMR (162 MHz, CDCl3) 4.19; HRMS (ESI):
[MþþH], found 370.1210. C20H20NO4P requires 370.1209.
(0.338 g, 0.97 mmol) and propargyl alcohol 21 (0.25 g, 0.97 mmol)
were dissolved in dry toluene (5 mL) at rt. The resulting solution
was heated with stirring at 70 ꢁC for 8 h. The crude product was
purified by column chromatography (hexane/EtOAc; 3:2) affording
22 as a pure white solid. This was crystallized from ethyl acetate.
Yield 0.434 g (84%); mp 202e206 ꢁC; Rf (40% EtOAc/hexane) 0.35;
nmax (KBr) 3337, 3245, 2975, 2928, 2857, 2631, 1757, 1618, 1543,
Compound 28. White solid; yield 0.108 g (12%); mp 78e80 ꢁC; Rf
(40% EtOAc/hexane) 0.59; nmax (KBr) 3063, 2959, 2926, 2855, 1655,
1491, 1368, 1209, 1140, 1078, 885, 762 cmꢀ1
; dH (400 MHz, CDCl3)
7.39 (d, J¼7.6 Hz, 1H), 7.09 (wdd, 1H), 6.82 (wdd, 1H), 6.61 (d,
J¼7.6 Hz, 1H), 4.39 (s, 1H), 3.04 (d, J¼3.6 Hz, 1H), 2.99e2.80 (m, 2H),
2.21e1.67 (m, 7H), 1.49, 1.44, 1.32 (3s, 27H); dC (100 MHz, CDCl3)
171.1, 142.29, 142.25, 131.5, 128.9, 120.4, 117.3, 115.6, 91.0, 52.8 (d,
J¼4.0 Hz), 52.5 (d, J¼4.0 Hz), 52.2 (d, J¼7.0 Hz), 38.6 (d, J¼141.0 Hz),
37.1, 35.1, 33.4, 32.6, 32.3, 24.3, 23.9, 22.3; 31P NMR (162 MHz,
CDCl3) 74.31 (slightly broad), 10.28 (d, J¼5.2 Hz); HRMS (ESI):
[MþþNa], found 555.2630. C27H42N4O3P2 requires 555.2630. X-ray
structure was determined for this compound.
1523, 1463, 1370, 1299, 1271, 1129, 1052, 1014, 855 cmꢀ1
; dH
(400 MHz, CDCl3) 7.87 (d, J¼8.0 Hz, 1H, AreH), 7.72 (dd, 1H, AreH),
7.63 (d, J¼7.6 Hz, 1H, AreH), 7.46e7.25 (m, 5H, AreH), 6.69 (d,
J¼3.2 Hz, 1H, AreH), 3.67e3.49 (m, 4H, OCH2), 1.26, 0.61 (2s, 6H,
CH3); dC (100 MHz, CDCl3) 141.8, 138.3, 133.0, 130.4, 129.2, 128.7,
128.2, 124.0, 122.7, 120.8, 114.2, 109.6, 77.8, 77.7, 31.9, 22.0, 20.1; 31
P
NMR (162 MHz, CDCl3) ꢀ10.68; HRMS (ESI): [MþþNa], found
364.1076. C19H20NO3P requires 364.1079. Passing this compound
(0.10 g, 0.29 mmol) through a basic alumina column afforded the
indole 17 (0.0512 g, 90%; see above24).
4.3.7. [(i-PrNH)P(
droacridine 24. The procedure was similar to that for compound 22
using [(i-PrNH)P( -N-t-Bu]2 (4c) [ (P) 90.7; 0.329 g,1.03 mmol] and
m-N-t-Bu)2P(O){C15H14NO2}] 23 and the tetrahy-
4.4.2. Compounds 29 and 30. The procedure was similar to that for
compound 15 using P(III)eCl precursor 5 (0.314 mL, 2.27 mmol),
propargyl alcohol 25 (0.268 g, 1.08 mmol), and NEt3 (0.332 mL,
2.27 mmol) The reaction time was 6 h at 70 ꢁC. The eluent was
hexane/EtOAc (3:2) to obtain solids 29 (eluted second) and 30
(eluted first).
m
d
propargyl alcohol 21 (0.22 g, 0.86 mmol). The reaction time was 8 h
and the eluent for column chromatography was hexane/EtOAc
(2:1). White solid; yield 0.276 g (62%); mp 192e196 ꢁC; Rf (30%
EtOAc/hexane) 0.49; nmax (KBr) 3343, 3241, 3117, 2969, 2930, 2863,
1757, 1616, 1491, 1399, 1366, 1262, 1209, 1132, 1076, 1015, 986, 887,
Compound 29. Yellow solid; yield 0.159 g (40%); mp 170e172 ꢁC;
[found: C, 62.71; H, 7.18; N, 3.91. C19H26NO4P requires C, 62.80; H,
7.21; N, 3.85%]; Rf (40% EtOAc/hexane) 0.4; nmax (KBr) 3278, 2963,
760 cmꢀ1
;
dH (400 MHz, CDCl3) 7.40 (d, J¼6.8 Hz, 1H), 7.10 (dd, 1H),
6.83 (dd, 1H), 6.62 (d, J¼8.0 Hz, 1H), 4.37 (s, 1H), 3.53 (s, 1H),
3.04e2.85 (m, 3H), 2.22e1.67 (m, 7H), 1.48, 1.43 (2s, 18H), 1.19, 1.17
(2s, 6H); dC (100 MHz, CDCl3) 171.1, 142.3, 131.6, 129.0, 120.5, 117.3,
115.6, 91.0, 52.8, 52.5, 44.9 (d, J¼26.0 Hz), 38.3 (d, J¼143.0 Hz), 37.2,
35.2, 33.3, 32.4, 32.2, 26.2, 24.4, 23.9, 22.3; 31P NMR (162 MHz,
CDCl3) 78.90, 10.22 (P(O)eC); HRMS (ESI): [MþþH], found
519.2654. C26H40N4O3P2 requires 519.2655. When compound 22
(0.25 g) was heated with toluene/water (9:1) mixture at 110 ꢁC/
12 h, tetrahydroacridine 24 could be isolated (0.031 g, ca. 36%). It is
a known compound.16a The values of dH and dC were identical to
that reported before (see Supplementary data). HRMS (ESI):
[MþþH], found 184.1124. C13H13N requires 184.1127.
2932, 1711, 1622, 1470, 1260, 1057, 1015, 797 cmꢀ1
; dH (400 MHz,
CDCl3) 8.64 (s, 1H), 8.31 (d, J¼8.0 Hz, 1H), 7.24e6.95 (m, 2H), 6.78
(d, J¼8.0 Hz, 1H), 4.28e3.86 (m, 4H), 3.32e3.23 (m, 2H), 1.66e1.23
(m, 6H), 1.15 (s, 3H), 1.05 (s, 3H), 0.90 (t, 3H); dC (100 MHz, CDCl3)
168.7 (d, J¼27.8 Hz), 141.6 (d, J¼162.8 Hz), 141.3, 135.6, 135.5, 130.9,
127.3, 122.2, 120.9, 109.4, 76.0 (d, J¼6.1 Hz), 32.6 (d, J¼5.6 Hz), 32.2,
29.7 (d, J¼77.3 Hz), 22.4, 21.7, 21.6, 14.1; 31P NMR (162 MHz, CDCl3)
11.13; LC/MS m/z 362 [Mꢀ1]þ; HRMS (ESI): [MþþH], found
364.1676. C19H26NO4P requires 364.1678.
Compound 30. White solid; yield 0.121 g (33%); mp 68e70 ꢁC;
[found: C, 64.58; H, 7.76; N 4.25. C18H26NO3P requires C, 64.46; H,
7.81; N, 4.18%]; Rf (40% EtOAc/hexane) 0.6; nmax (KBr) 2959, 2932,
4.4. Synthesis of phosphorus containing and phosphorus free
1586, 1564, 1454, 1375, 1302, 1155, 1123, 1057, 1009, 947 cmꢀ1
; dH
N-heterocycles [26e32], [35e47]
(400 MHz, CDCl3) 7.76 (d, J¼8.4 Hz, 1H), 7.51 (d, J¼7.2 Hz, 1H),
7.27e7.19 (m, 2H), 6.47 (d, J¼3.2 Hz, 1H), 4.17e3.95 (m, 4H), 2.91 (t,
2H), 1.83e1.41 (m, 6H), 1.38 (s, 3H), 0.93 (t, 3H), 0.87 (s, 3H); dC
(100 MHz, CDCl3) 143.22, 143.16, 138.2, 138.1, 130.9, 130.7, 129.1,
128.3, 123.1, 122.3, 120.2, 113.4, 107.05, 106.96, 78.1 (d, J¼6.6 Hz),
32.4 (d, J¼5.6 Hz), 31.7, 28.6, 28.1, 22.6, 22.0, 20.7, 14.1; 31P NMR
(162 MHz, CDCl3) ꢀ8.87; LC/MS m/z 336 [Mþ1]þ.
4.4.1. Compounds 26e28 (and 17). The procedure was same as that
for compound 15 using P(III)eCl precursor 525 (0.681 mL,
4.93 mmol), propargyl alcohol 10 (0.595 g, 2.35 mmol), and NEt3
(0.687 mL, 4.93 mmol). The reaction time was 8 h at 70 ꢁC. The
reaction mixture showed 26þ27 (total 71%) along with 28 (ca. 12%).
Using hexane/EtOAc (3:2) mixture as the eluent, we isolated
compounds 26 (eluted last), 27 (eluted second), and 28 (eluted
first).
4.4.3. Compound 31. This product was obtained by adapting the
procedure same as that for compound 15 by using P(III)eCl pre-
cursor 5 (0.532 mL, 3.85 mmol), propargyl alcohol 18 (0.458 g,
1.84 mmol), and NEt3 (0.56 mL, 3.85 mmol). Reaction time was 8 h
Compound 26. Yellow solid; yield 0.381 g (31%); mp 196e198 ꢁC;
[found: C, 58.12; H, 5.61; N, 2.65. C25H29NO7P2 requires C, 58.03; H,

G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
2651
at 70 ꢁC. It was isolated by column chromatography [hexane/ethyl
acetate (2:3)] as a white solid. Yield 0.327 g (61%); mp 296e298 ꢁC;
[found: C, 57.19; H, 5.56; N, 4.68. C14H16NO4P requires C, 57.34; H,
5.50; N, 4.78%]; Rf (60% EtOAc/hexane) 0.3; nmax (KBr) 3160, 3106,
3054, 3019, 2965, 2897, 1651, 1561, 1497, 1476, 1429, 1372, 1240,
CDCl3) 28.52; HRMS (ESI): [MþþH], found 432.1722. C26H26NO3P
requires 432.1729.
Compound 39. Brown gummy liquid; yield 0.108 g (28%); [found:
C, 77.65; H, 6.72; N, 3.71. C25H26NOP requires C, 77.50; H, 6.76; N,
3.62%]; Rf (40% EtOAc/hexane) 0.67; nmax (neat) 3054, 2928, 2857,
1155, 1134, 1076, 1020, 947 cmꢀ1
;
dH (400 MHz, CDCl3) 11.73 (s, 1H),
1583, 1453, 1229, 1125, 1053, 729 cmꢀ1
; dH (400 MHz, CDCl3)
8.76 (d, J¼18.0 Hz, 1H), 7.71e7.27 (m, 4H), 4.76e4.12 (m, 4H), 1.39,
1.14 (2s, 6H); dC (125 MHz, CDCl3) 163.1, 151.8 (d, J¼8.4 Hz), 140.1,
133.0, 129.7, 123.3, 120.9, 119.1, 119.0, 115.6, 77.8 (d, J¼6.9 Hz) 32.9
(d, J¼9.0 Hz), 22.5, 21.2; 31P NMR (162 MHz, CDCl3) 6.06; LC/MS m/z
292 [Mꢀ1]þ.
7.67e7.46 (m, 11H), 7.08 (t, 1H), 6.82 (t, 1H), 6.56 (d, J¼8.4 Hz, 1H),
6.51 (s, 1H), 2.73 (t, 2H), 1.63e1.21 (m, 6H), 0.82 (t, 3H); dC
(100 MHz, CDCl3) 146.4, 139.6, 132.9, 132.4, 132.1, 132.0, 131.1, 130.9,
129.0, 128.9, 121.9, 121.6, 119.8, 114.3, 106.94, 106.88, 31.4, 29.7, 28.5,
22.4,14.0; 31P NMR (162 MHz, CDCl3) 26.11; LC/MS m/z 388 [Mþ1]þ.
4.4.4. Compound 32. Passing compound 30 (0.11 g, 0.33 mmol)
through a basic alumina column afforded the indole 32 as a white
solid. Rf (10% EtOAc/hexane) 0.54; yield: 0.052 g (84%). It is a known
compound (see Supplementary data for NMR spectra).24
4.4.7. Compound 40. The procedure was similar to that for com-
pound 15 using Ph2PCl (6) (0.474 mL, 2.64 mmol), propargyl alcohol
33 (0.62 g, 2.20 mmol), and NEt3 (0.368 mL, 2.64 mmol). The re-
action time was 4 h at 70 ꢁC and the eluent was hexane/EtOAc (3:2)
to obtain compound 40 as a white crystalline solid. Yield 0.632 g
(62%); mp 142e144 ꢁC (bubbling); Rf (40% EtOAc/hexane) 0.43; nmax
(KBr) 2953, 2915, 2871, 2844, 1737, 1479, 1441, 1370, 1216, 1118,
4.4.5. Compounds 35 and 36. The procedure was similar to that for
compound 15 using Ph2PCl (6) (0.396 mL, 2.21 mmol), propargyl
alcohol 10 (0.47 g, 1.84 mmol), and NEt3 (0.31 mL, 2.21 mmol). The
reaction time was 4 h at 70 ꢁC and the eluent was hexane/EtOAc
(3:2) to obtain compounds 35 (eluted second) and 36 (eluted first).
888 cmꢀ1
; dH (400 MHz, CDCl3) 8.04e7.16 (m, 13H), 7.02 (s, 1H),
2.69e2.24 (m, 2H), 1.36e1.33 (m, 6H), 0.94 (t, 3H); dC (125 MHz,
CDCl3) 170.4 (d, J¼5.0 Hz), 138.7, 137.1, 135.04, 134.96, 134.1, 133.8,
133.1, 133.0, 132.5, 132.4, 132.3, 132.2, 130.2, 129.9, 129.7, 128.9,
128.8, 128.6, 128.4, 126.19, 126.16, 35.5, 31.6, 28.8, 22.5, 14.1; 31P
NMR (162 MHz, CDCl3) 28.65; HRMS (ESI): [MþþH and MþþHþ2],
found 466.1337 and 468.1287. C26H25ClNO3P requires 466.1340 and
468.1340.
Compound 35. Yellow solid; yield 0.235
224e226 ꢁC; Rf (40% EtOAc/hexane) 0.36; nmax (KBr) 3134, 3068,
2921, 2849, 1715, 1616, 1468, 1436, 1326, 1211, 1151, 1118, 921 cmꢀ1
g (30%); mp
;
dH (400 MHz, CDCl3) 8.36 (d, J¼8.0 Hz, 1H, AreH), 8.03 (br s, 1H,
NH), 7.60e6.62 (m, 18H, AreH); dC (100 MHz, CDCl3) 166.9 (d,
J¼17.0 Hz, C]O), 143.5 (d, 1J(PeC)¼84 Hz, PC), 142.5, 138.6, 137.5,
137.4, 132.2, 132.1, 132.0, 131.6, 131.4, 130.3, 129.9, 128.5, 128.3,
128.1, 128.0, 127.9, 127.0, 122.2, 120.6, 109.6; 31P NMR (162 MHz,
CDCl3) 30.67; HRMS (ESI): [MþþH], found 422.1309. C27H20NO2P
requires 422.1311.
4.4.8. Compounds 41 and 42. The procedure was similar to that for
compound 15 using Ph2PCl (6) (0.269 mL, 1.50 mmol), propargyl
alcohol 34 (0.407 g, 1.25 mmol), and NEt3 (0.21 mL, 1.50 mmol). The
reaction time was 4 h at 70 ꢁC and the eluent was hexane/EtOAc
(3:2) to obtain compounds 41 (eluted second), 42 (eluted first).
Compound 41. White crystalline solid; yield 0.294 g (26%); mp
148e150 ꢁC (bubbling); Rf (40% EtOAc/hexane) 0.5; nmax (KBr) 3058,
2953, 2921, 2855, 1742, 1611, 1595, 1474, 1436, 1364, 1222, 1123,
Compound 36. Brown colored gummy liquid; yield 0.376 g (52%);
Rf (40% EtOAc/hexane) 0.59; nmax (neat) 3058, 2926, 2849, 1594,
1436, 1310, 1255, 1222, 1123, 1074, 1008, 811 cmꢀ1
; dH (400 MHz,
CDCl3) 7.61e6.97 (m, 19H, AreH), 6.64 (d, J¼4.0 Hz, 1H, AreH); dC
(100 MHz, CDCl3) 144.14, 144.10, 140.78, 140.75, 133.4, 132.38, 132.36,
132.2, 132.1, 130.9, 130.6, 130.5, 130.04, 129.98, 128.6, 128.44, 128.35,
128.3, 127.6, 127.5, 123.1, 122.4, 120.5, 116.2, 110.9, 110.8; 31P NMR
(162 MHz, CDCl3) 23.83; HRMS (ESI): [MþþH], found 394.1360.
1058, 992, 882 cmꢀ1
; dH (400 MHz, CDCl3) 8.03e7.76 (m, 4H),
7.62e7.29 (m, 9H), 7.01 (s, 1H), 2.69e2.24 (m, 2H), 1.38e1.32 (m,
6H), 0.93 (t, 3H); dC (100 MHz, CDCl3) 170.4 (d, J¼4.0 Hz), 139.2,
137.2, 135.33, 135.25, 134.0, 133.2, 133.1, 133.0, 132.6, 132.5, 132.4,
132.3, 132.2, 129.9, 129.7, 129.0, 128.8, 128.6, 128.4, 126.42, 126.39,
121.7, 35.5, 31.6, 28.8, 22.5, 14.1; 31P NMR (162 MHz, CDCl3) 28.83;
HRMS (ESI): [MþþH and MþþHþ2], found 510.0831 and 512.0815.
C
26H20NOP requires 394.1362.
4.4.6. Compounds 37e39. The procedure was similar to that for
compound 15 using Ph2PCl (6) (0.381 mL, 2.12 mmol), propargyl
alcohol 25 (0.25 g, 1.01 mmol), and NEt3 (0.311 mL, 2.12 mmol). The
reaction time was 4 h at 70 ꢁC and the eluent was hexane/EtOAc
(3:2) to obtain compounds 37 (eluted last), 38 (eluted second), and
39 (eluted first).
C26H25BrNO3P requires 510.0834 and 512.0834.
Compound 42. Green gummy liquid; yield 0.637 g (62%); Rf (40%
EtOAc/hexane) 0.59; nmax (neat) 2959, 2926, 2844, 1589, 1436, 1271,
1227, 1123 cmꢀ1
;
dH (400 MHz, CDCl3) 7.64e7.47 (m, 11H, AreH),
6.92 (d, J¼8.8 Hz, 1H, AreH), 6.48 (d, J¼8.8 Hz, 1H, AreH), 6.44 (1s,
1H, AreH), 2.66 (t, 2H, CH2), 1.64e1.56 (m, 2H, CH2), 1.20e1.16 (m,
4H, CH2), 0.81 (t, 3H, CH3); dC (100 MHz, CDCl3) 147.8, 138.4, 133.2,
132.8,132.7,132.1,132.0,131.9,130.6,129.2,129.0,124.7,122.4,115.7,
115.1, 106.3, 106.2, 31.4, 29.7, 28.4, 22.4, 14.0; 31P NMR (162 MHz,
CDCl3) 26.51; HRMS (ESI): [MþþH and MþþHþ2], found 466.0936
and 468.0919. C25H25BrNOP requires 466.0936 and 468.0936.
Compound 37. Brown colored gummy liquid; yield 0.112 g (26%);
Rf (40% EtOAc/hexane) 0.33; nmax (neat) 3346, 3072, 2928, 2859,
1713, 1622, 1470, 1435, 1327, 1173, 1105, 1022, 752 cmꢀ1
; dH
(400 MHz, CDCl3) 8.27 (d, J¼8.0 Hz, 1H), 7.82 (br s, 1H), 7.78e6.68
(m, 13H), 2.90 (br, 2H), 1.43e0.86 (m, 6H), 0.71 (t, 3H); dC (125 MHz,
CDCl3) 168.3 (d, J¼18.8 Hz), 147.6 (d, J¼81.3 Hz), 141.1, 137.0, 132.34,
132.32, 132.23, 132.15, 131.9, 131.1, 130.5, 129.3, 128.7, 128.6, 122.0,
121.3, 121.2, 116.2, 109.1, 32.0, 31.6 (d, J¼7.5 Hz), 28.5, 21.9, 14.0; 31
P
4.4.9. Compounds 43e45. In a round bottomed flask equipped
with 0.18 g (0.42 mmol) of phosphono-heterocycle 38, toluene/
water mixture (2 mL; 9:1 v/v) was added and the content was
heated with stirring at 110 ꢁC for 8 h. After the completion of the
reaction (TLC), the solvent was removed under reduced pressure.
The crude product was purified by column chromatography (hex-
ane/EtOAc; 9:1) affording 43. Compounds 44 and 45 were prepared
similarly.
Compound 43. Yield 0.054 g (59%); Rf (10% EtOAc/hexane) 0.55; It
is a known compound.18 HRMS and X-ray structure were not re-
ported for this compound. HRMS (ESI): [MþþH], found 216.1389.
NMR (162 MHz, CDCl3) 33.61; HRMS (ESI): [MþþH], found 416.1774.
C
26H26NO2P requires 416.1780.
Compound 38. White solid; yield 0.083 g (20%); mp 98e100 ꢁC
(bubbling); Rf (40% EtOAc/hexane) 0.5; nmax (KBr) 3052, 2959, 2921,
2855, 1726, 1622, 1589, 1436, 1216, 1195, 1118, 1063, 975, 762 cmꢀ1
;
dH (400 MHz, CDCl3) 8.07e7.19 (m, 14H), 7.11 (s, 1H), 2.69e2.24 (m,
2H), 1.36 (br s, 6H), 0.94 (t, 3H); dC (125 MHz, CDCl3) 171.0 (d,
J¼3.8 Hz), 140.2, 135.8, 135.5, 133.63, 133.56, 132.9, 132.87, 132.85,
132.6, 130.5, 132.4, 132.3, 130.7, 130.1, 130.0, 129.1, 128.9, 128.8,
128.7, 128.2, 124.9, 35.6, 31.7, 29.0, 22.6, 14.2; 31P NMR (162 MHz,

2652
G. Gangadhararao, K.C. Kumara Swamy / Tetrahedron 70 (2014) 2643e2653
C14H17NO requires 216.1389. X-ray structure was determined for
this compound.
(1.0 mL, 7.16 mmol) in THF (20 mL) was stirred at 0 ꢁC for 5 min, and
then [ClPeN(t-Bu)]2 (4a) (0.985 g, 3.58 mmol) dissolved in THF
(20 mL) was added drop-wise at 0 ꢁC (20 min). The mixture was
warmed to rt (25 ꢁC) and then heated with stirring at 60 ꢁC for 10 h.
The mixture was filtered and solvent was removed under reduced
pressure. The residue was treated with ethyl acetate when white
crystalline compound 48 settled down at the bottom of the flask.
This compound was crystallized from ethyl acetate/chloroform
mixture (1:2). Yield 1.14 g (74%); mp 210e214 ꢁC; Rf (25% EtOAc/
hexane) 0.48; nmax (KBr) 2984, 1734, 1476, 1431, 1373, 1281, 1223,
Compound 44. White solid; yield 0.042 g (68% using 0.116 g,
(0.25 mmol) of phosphono heterocycle 40); mp 158e160 ꢁC; Rf (10%
EtOAc/hexane) 0.46; nmax (KBr) 3156, 2992, 2959, 2926, 2855, 1666,
1573, 1479, 1414, 1370, 1216, 1079, 942 cmꢀ1
; dH (400 MHz, CDCl3)
11.12 (br s, 1H, NH), 7.52 (s, 1H, AreH), 7.51 (d, J¼2.4 Hz, 1H, AreH),
7.41e7.38 (m, 1H, AreH), 7.25 (d, J¼8.4 Hz, 1H, AreH), 2.66 (t, 2H,
CH(CH2)), 1.72e1.65 (m, 2H, CH2), 1.42e1.39 (m, 4H, CH2), 0.93 (t,
3H, CH3); dC (100 MHz, CDCl3) 164.2 (C]O), 135.9, 135.4, 129.5,
127.7, 126.3, 121.4, 117.0, 31.7, 30.3, 28.0, 22.6, 14.1; HRMS (ESI):
[MþþH and MþþHþ2], found 250.1000 and 252.0963. C14H16ClNO
requires 250.0999 and 252.0999.
1111, 1047, 1020, 995, 943, 910, 824 cmꢀ1
; dH (400 MHz, CDCl3) 2.77
(s, 8H), 1.46 (s, 18H); dC (100 MHz, CDCl3) 175.8, 58.3, 30.1, 29.8; 31
P
NMR (162 MHz, CDCl3) ꢀ17.34; HRMS (ESI): (MþþH), found
433.1407. C16H26N4O6P2 requires 433.1407. X-ray structure was
determined for this compound.
Compound 45. White solid; yield 0.085 g (64%; using 0.23 g
(0.47 mmol) of phosphono heterocycle 41); mp 148e150 ꢁC; Rf (10%
EtOAc/hexane) 0.53; nmax (KBr) 3151, 2959, 2915, 2849, 1666, 1616,
X-ray data for 9a, 12, 13, 15, 16, 19, 22, 26, 29, 40, 43, and 48 were
1573, 1474, 1414, 1370, 1255, 1205, 1063, 932 cmꢀ1
;
dH (400 MHz,
collected on Bruker AXS SMART or OXFORD diffractometer at 296 K
ꢀ
CDCl3) 11.03 (br s, 1H, NH), 7.66 (s, 1H, AreH), 7.53e7.51 (m, 2H,
AreH) 7.18 (d, J¼8.8 Hz, 1H, AreH), 2.66 (t, 2H, CH2), 1.70e1.62 (m,
2H, CH2), 1.40e1.38 (m, 4H, CH2), 0.93 (t, 3H, CH3); dC (100 MHz,
CDCl3) 163.8 (C]O), 136.2, 135.9, 135.3, 132.2, 129.5, 121.9, 117.1,
115.0, 31.7, 30.3, 28.0, 22.6, 14.1; HRMS (ESI): [MþþH and
MþþHþ2], found 294.0494 and 296.0477. C14H16BrNO requires
294.0494 and 296.0494.
using Mo-Ka
(
l
¼0.71073 A) radiation. The structures were solved
by direct methods and refined by full matrix least-squares methods
using standard procedures.26 Absorption corrections were done
using the SADABS program, where applicable. All non-hydrogen
atoms were refined anisotropically. The hydrogen atoms were
fixed by geometry or located by difference Fourier map; sub-
sequently a riding model was used. Some of the methyl carbon
atoms of the tert-butyl groups in these compounds have high
thermal parameters, but these do not affect the overall structure
around cyclophosphazane skeleton and hence we have not tried to
model them rigorously. Data quality was moderate for 43. Specifi-
cally, in the structures of compounds 12, and 16, disorder is found at
the tert-butyl carbons attached to C9 and (N4, C24, C28) re-
spectively. Crystallographic data as well as CCDC numbers are
summarized in Table S1aec for compounds 9a, 12, 13, 15, 16, 19, 22,
26, 29, 40, 43, and 48 in the Supplementary data.
4.4.10. Compounds 17, 32, 46, and 47. In a round bottomed flask
equipped with 0.20 g (0.51 mmol) of phosphono indole 36, 1 g of
basic alumina and 3 mL of ethyl acetate were added. Then the
mixture was stirred at rt for 15 h. After the completion of the re-
action (TLC), the mixture was filtered and the solvent was removed
under reduced pressure. The crude product was purified by column
chromatography (hexane/EtOAc; 9:1) affording 17 as a white solid
(known compound;24 also see above). Yield 0.086 g (88%). Com-
pound 32 was prepared by passing 39 through alumina column
using hexane/ethyl acetate (4:1). Yield 0.084 g [87%; using 0.28 g
(0.52 mmol) of phosphono-indole 39; also see above in 4.4.4].
Acknowledgements
Compound 46. The phosphorus precursor (similar to 39) [d(P)
We thank the Department of Science and Technology (DST, New
Delhi) for financial support and for setting up of the National Single
Crystal Diffractometer Facility at the University of Hyderabad. We
also thank UPE program of the University Grants Commission (UGC,
New Delhi) for equipment. G.G. also thanks CSIR for a fellowship.
26.56] of 46 could be isolated in only 95% purity, but 46 could be
readily obtained from this by passing through a basic alumina
column [hexane/ethyl acetate (9:1)]. Pale yellow solid; yield 0.065 g
(92%; using 0.134 g (0.32 mmol) of corresponding phosphono in-
dole); mp 40e42 ꢁC; Rf (10% EtOAc/hexane) 0.71; nmax (KBr) 3403,
2932, 2849, 1463, 1447, 1408, 1085, 871 cmꢀ1
; dH (400 MHz, CDCl3)
Supplementary data
7.89 (br s, 1H, NH), 7.50 (1s, 1H, AreH), 7.20e7.06 (m, 2H, AreH),
6.20 (1s, 1H, AreH), 2.74 (t, 2H, CH2), 1.76e1.71 (m, 2H, CH2),
1.40e1.36 (m, 4H, CH2), 0.93 (t, 3H, CH3); dC (100 MHz, CDCl3) 141.7,
134.2, 130.1, 125.2, 121.1, 119.2, 111.3, 99.3, 31.5, 28.8, 28.3, 22.5, 14.1;
HRMS (ESI): [MþþH and MþþHþ2], found 222.1046 and 224.1013.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.02.064.
References and notes
C
13H16ClN requires 222.1050 and 224.1050.
Compound 47. This was isolated by passing a solution of 42 in
1. (a) Mark, V. Tetrahedron Lett. 1962, 3, 281; (b) Boisselle, A. P.; Meinhardt, N. A. J.
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3397, 2959, 2921, 2849, 1567, 1452, 1408, 1315, 1260, 1052,
877 cmꢀ1
; dH (400 MHz, CDCl3) 7.86 (br s, 1H, NH), 7.68 (1s, 1H,
2. Selected recent book/reviews: (a) Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; pp 760e787; (b) Ma, S.
Aldrichimica Acta 2007, 40, 91; (c) Ma, S. Acc. Chem. Res. 2009, 42, 1679; (d)
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CH2), 1.76e1.69 (m, 2H, CH2), 1.41e1.35 (m, 4H, CH2), 0.96 (t, 3H,
CH3); dC (100 MHz, CDCl3) 141.6, 134.5, 130.7, 123.6, 122.2, 112.7,
111.8, 99.1, 31.5, 28.8, 28.2, 22.5, 14.1; HRMS (ESI): [MþþH and
MþþHþ2], found 266.0545 and 268.0525. C13H16BrN requires
266.0545 and 268.0545.
€
ꢁ ꢁ
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4.5.1. {[eC(]O)eCH2eCH2eC(]O)e]eNeP(]O)eN-t-Bu}2 48. A
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fairly clear. Crystal dimensions (triclinic): a¼7.035(4), b¼7.764(3), c¼40.
3
ꢀ
ꢁ
631(18),
a
¼91.55(4),
b
¼93.22(5),
g
¼104.53(5) , V¼2142.8(18) A .
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group and the phosphorus are attached to the
change in these connectivities in the products 12e14. The
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the final products (12e14), the -carbon is still connected to the aryl group, but
the nitrogen gets connected to a carbonyl carbon, which should have been the
-carbon in II. However, there is no NMR evidence in the current study to
a
-carbon. There has been no
g
-carbon in the al-
g
b
actually support the atomic rearrangement due to the lack of the appropriately
13C labeled precursor.
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14. We wish to mention that, in addition to the cyclophosphazanyl-allene 9,
we have isolated another minor PeC bonded enamine product 9a (ca. 34%;
Fig. S12) resulting from the nucleophilic addition of liberated isopropyl-
amine to the allene 9. Such reactions have been reported by us before. See:
Trans. 1 1973, 379.
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€