Di-μ-hydroxy-bis(N,N,N′,N′-tetramethylenediamine)copper(II) chloride {[Cu(OH)·TMEDA]2Cl2} catalyzed tandem phosphorous-carbon bond formation-oxyfunctionalization: Efficient Synthesis of phenacyl tertiary phosphine-boranes

Article abstract of DOI:10.1055/s-0028-1088120

A novel [Cu(OH)·TMEDA]₂Cl₂ catalyzed tandem reaction has been developed for the synthesis of a series of sterically and electronically divergent phenacyl tertiary phosphine-boranes. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088120

1180
LETTER
Di-m-Hydroxy-bis(N,N,N¢,N¢-tetramethylenediamine)copper(II) Chloride
{[Cu(OH)·TMEDA]2Cl2} Catalyzed Tandem Phosphorous–Carbon Bond
Formation–Oxyfunctionalization: Efficient Synthesis of Phenacyl Tertiary
Phosphine-Boranes
S
ynthesis of Phena
u
cyl
T
ertiary
l
Phosph
l
ine-B
o
a
ranes palli Kumaraswamy,*a Gadde Venkata Rao,a Akula Narayana Murthy,a Balasubramanian Sridharb
a
Organic Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27193275; E-mail: gkswamy_iict@yahoo.co.in
Laboratory of X-ray Crystallography, Indian Institute of Chemical Technology, Hyderabad 500 007, India
b
Received 2 January 2009
ipated vinyl phosphine-borane product was not formed;
instead the phenacyl tertiary phosphine-borane 3b was
isolated in 30% yield. A control reaction conducted with-
out CuI was unsuccessful. After exploring several copper
salts8 and reaction conditions9 it was found that 10 mol%
of [Cu(OH)·TMEDA]2Cl2 and 20 mol% of Et3N as a base
in an open system,10 stirring at ambient temperature in
acetonitrile, afforded the phenacyl tertiary phosphine-
borane 3b in an 80% yield (Scheme 1).11
Abstract: A novel [Cu(OH)·TMEDA]2Cl2 catalyzed tandem reac-
tion has been developed for the synthesis of a series of sterically and
electronically divergent phenacyl tertiary phosphine-boranes.
Key words: phosphine-boranes, terminal alkynes, phenacyl tertia-
ry phosphine-borane, copper iodide, methyl propiolate
The functionalization of substituted aryl terminal alkynes
and olefins by an activated-hydrogen-containing hetero-
atom is of fundamental importance in terms of synthetic
value as well as atom economy.1 Among such processes,
the construction of carbon–phosphorus bonds has an in-
triguing potential due to their use as ligands in transition-
metal-catalyzed reactions.2 In particular, phosphine-
boranes are the requisite precursors for the synthesis of
tunable ligands. Recently, efficient approaches have been
reported for the regioselective addition to terminal
alkynes. Many of these protocols are via a metal-
catalyzed P–H activation, particularly by palladium,3
rhodium,4 and organolanthanide5 followed by their sub-
sequent addition to terminal alkynes leading to stereo-
defined vinyl phosphine-borane derivatives.
BH3
BH3
O
[Cu(OH)⋅TMEDA]2Cl2 (10 mol%)
P
R1
P
R1
Ph
H
Ph
Et3N (20 mol%)
R2
2a
MeCN, r.t., 6 h
3b R1 = t-Bu, 80%
( )-1a R1 = Me
( )-1c R1 = Ph
( )-1b R1 = t-Bu
( )-1d R1 = OMe
Scheme 1
The structure of phenacyl tertiary phosphine-borane 3b
1
was determined by H NMR, 13C NMR, and mass spec-
An excellent regio- and stereocontrolled thermally acti-
vated hydrophosphination of simple alkynes with second-
ary phosphine-borane has also been reported on the gram
scale, leading to b-addition vinyl phosphine-borane ad-
ducts.6 Recently, we have demonstrated a mild and effi-
cient protocol for phosphorous–carbon bond formation
with a substoichiometric amount of copper for the synthe-
sis of scalemic tertiary phosphine-boranes.7 Herein, we
report to the best of our knowledge, the first
[Cu(OH)·TMEDA]2Cl2 catalyzed tandem phosphorous–
carbon bond formation–oxyfunctionalization of terminal
aryl-substituted alkynes and aryl olefins resulting in the
synthesis of phenacyl tertiary phosphine-boranes. At the
outset, we explored this transformation using phosphine-
borane ( )-1b (1.1 equiv) and phenyl acetylene (2a, 1
equiv) in the presence of 10 mol% of CuI in acetonitrile,
stirring at ambient temperature. To our surprise, the antic-
trometry and was finally established by X-ray crystallog-
raphy (Figure 1).
Figure 1 X-ray crystal structure of 3b1,2
Encouraged by this result, the scope of this new reaction
was investigated with substituted phenylacetylene and
phosphine-boranes. The results are summarized in
Table 1. Various phosphine-boranes were coupled with a
wide range of substituted phenylacetylenes irrespective of
the steric and electronic nature of aromatic nucleus and
further oxidation led to the corresponding phenacyl tertia-
ry phosphine-boranes in moderate to good yields. For ex-
ample, under the standard conditions, 3,4-dimethoxy
SYNLETT 2009, No. 7, pp 1180–1184
x
x.
x
x.
2
0
0
9
Advanced online publication: 26.03.2009
DOI: 10.1055/s-0028-1088120; Art ID: D00309ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Phenacyl Tertiary Phosphine-Boranes
1181
phenylacetylene (2c) reacted with ( )-1b leading to the b-addition products 13a–d were isolated with E-
desired product 5a in 90% yield where as 2-amino-5-nitro selectivity6a (Scheme 2).
phenylacetylene 2e with ( )-1b furnished the desired
product 7b, albeit in moderate yield (65%). The 2-meth-
oxy-5-tert-butylphenylacetylene (2d) also underwent
phosphination–oxygenation with ( )-1b and the resulting
product 6b was isolated in 80% yield. The heteroatom-
containing 3-pyridylacetylene and ( )-1b was subjected
to an identical protocol, and the anticipated product 11a
resulted in 80% yield but, with 2-pyridylacetylene, the ex-
pected product was not formed. Interestingly, 1,3-diethi-
nylbenzene (2f) also underwent coupling–oxygenation
with 2.2 equivalents of ( )-1a and the corresponding 1,3-
substituted tertiary phosphine-borane 8a was isolated in
85% yield. Surprisingly, a fast and efficient hydrophos-
phination–oxidation reaction was brought about using ac-
tivated alkenes. Thus, phosphine-boranes ( )-1b were
allowed to react with styrene 2i under the same set of con-
ditions resulting in phenacyl tertiary phosphine-borane 3b
in 85% isolated yield. It was also observed that the phos-
phine-borane had coupled to the terminal carbon of acet-
ylene or olefin, and oxidation occurred at the benzylic
carbon maintaining complete regioselectivity leading to
the observed product. Under identical conditions, we also
examined the reaction of phosphine-boranes ( )-1a–d,
with Michael acceptor such as methyl propiolate. Only
BH3
O
BH3
[Cu(OH)⋅TMEDA]2Cl2 (10 mol%)
Et3N (20 mol%)
OMe
P
R1
P
R1
Ph
H
Ph
2m
CO2Me
MeCN, r.t., 1 h
13a R1 = Me, 95%
13b R1
( )-1a R1 = Me
( )-1c R1 = Ph
( )-1b R1 = t-Bu
( )-1d R1 = OMe
= t-Bu, 90%
13c R1 = Ph 92%
13d R1 = OMe, 80%
Scheme 2
The reaction mechanism remains to be explored but the
postulated catalytic cycle is shown in Scheme 3. The
monomeric Cu(II) catalyst B activates sequentially alkyne
and secondary phosphine-borane leading to the formation
of mixed Cu(II)–alkyne–phosphine-borane species D fol-
lowed by reductive elimination and subsequent hydrolysis
results in the observed product.13,14
In conclusion, we have succeeded in developing a Cu(II)–
TMEDA catalyzed tandem phosphorous–carbon bond
formation–oxyfunctionalization protocol for the synthesis
of a series of sterically and electronically divergent phen-
acyl tertiary phosphine-boranes. Further work is under
way to broaden the scope of this reaction.
H
O
N
N
N
N
Cu
Cu
BH3
2 Cl–
O
H
Et3N⋅HCl
O
1/2 O2
N
+
P
R1
Ph
R2
A
Cu0
2
H2O
BH3
BH3
P
N
N
OH
Cl
2
Cu
P
R1
N
R2
F
Ph
N
H
Ph
R1
Cu0
N
2
B
E
H2O
BH3
P
BH3
P
Ph
R1
N
Ph
R1
N
N
Cu
N
2
Cu
2
R2
Cl
D
C
+
R2
Et3NH
Et3N⋅HCl
Scheme 3
Synlett 2009, No. 7, 1180–1184 © Thieme Stuttgart · New York

1182
G. Kumaraswamy et al.
LETTER
Table 1 Cu-Catalyzed Hydrophosphination and Oxygenation of Aryl-Substituted Terminal Alkynes and Olefinsa
Acetylene
R2 =
Product,b yield (%)c
BH3
O
P
Ph
R1
3a R1 = Me, 85%
3c R1 = Ph, 80%
3d R1 = MeO, 75%
2a
BH3
O
P
R1
Ph
OMe
OMe
2b
4a R1 = Me, 72%
4b R1 = t-Bu, 78%
4c R1 = Ph, 85%
BH3
O
OMe
OMe
P
OMe
Ph
R1
OMe
2c
5a R1 = t-Bu, 90%
BH3
O
OMe
MeO
P
Ph
R1
t-Bu
t-Bu
6a R1 = Me, 78%
6b R1 = t-Bu, 80%
2d
BH3
O
NH2
H2N
P
Ph
R1
NO2
NO2
7a R1 = Me, 61%
7b R1 = t-Bu, 65%
2e
2f
O
O
H3B
BH3
R1
P
P
Ph
R1
Ph
8a R1 = Me, 85%
BH3
O
P
Ph
R1
2g
9a R1 = MeO, 75%
BH3
O
OMe
OMe
P
Ph
R1
10a R1 = Me, 85%
10b R1 = t-Bu, 80%
10c R1 = Ph, 82%
10d R1 = MeO, 75%
2h
Synlett 2009, No. 7, 1180–1184 © Thieme Stuttgart · New York

LETTER
Synthesis of Phenacyl Tertiary Phosphine-Boranes
1183
Table 1 Cu-Catalyzed Hydrophosphination and Oxygenation of Aryl-Substituted Terminal Alkynes and Olefinsa (continued)
Acetylene
R2 =
Product,b yield (%)c
3b R1 = t-Bu, 85%
2i
BH3
O
P
R1
Ph
N
N
2k
11a R1 = t-Bu, 80%
BH3
O
P
R1
Ph
Cl
Cl
2j
12a R1 = t-Bu, 90%
a All reactions were carried out with terminal alkyne (1 mmol), phosphine-borane (1.1 mmol) using 10 mol% of [Cu(OH)·TMEDA]2Cl2 and 20
mol% of Et3N in MeCN (5 mL) at ambient temperature and stirring for 6 h.
b All products were fully characterized.
c Unoptimized isolated yields.
(4) Reichwein, J. F.; Patel, M. C.; Pagenkopf, B. L. Org. Lett.
Supporting Information for this article is available online at
2000, 3, 4303.
http://www.thieme-connect.com/ejournals/toc/synlett.
(5) (a) Douglass, M. R.; Marks, T. J. J. Am. Chem. Soc. 2000,
122, 1824. (b) Douglass, M. R.; Stern, C. L.; Marks, T. J.
J. Am. Chem. Soc. 2001, 123, 10221. (c) Douglass, M. R.;
Ogasawara, M.; Hong, S.; Metz, M. V.; Marks, T. J.
Organometallics 2002, 21, 283.
(6) (a) Mimeau, D.; Gaumont, A. C. J. Org. Chem. 2003, 68,
7016. (b) Bourumeau, K.; Gaumont, A. C.; Denis, J. M.
Tetrahedron Lett. 1997, 38, 1923. (c) Bourumeau, K.;
Gaumont, A. C.; Denis, J. M. J Organomet. Chem. 1997,
529, 205.
Acknowledgment
We are grateful to Director of the IICT for his constant encourage-
ment. The DST, New Delhi (Grant No: SR/SI/OC-12/2007) is also
gratefully acknowledged for their financial assistance. GVR and
ANM are thankful to CSIR & UGC (New Delhi) for awarding the
fellowship.
(7) Kumaraswamy, G.; Venkata Rao, G.; RamaKrishna, G.
Synlett 2006, 1122.
Reference and Notes
(8) Other copper salts evaluated for this transformation are
CuOTf, CuOAc, CuCl, CuCl2, Cu(Piv)2, [Cu(MeCN)4]PF6,
and Cu(acac)2. Except CuCl2 (30%), none gave target
compound.
(9) Various solvents and bases were screened for the
optimization of yield of 3b. Halogenated solvents (CH2Cl2,
CHCl3, DCE) and toluene failed to give the product. In
addition to MeCN, only the aprotic solvent DMF was
successful albeit in low yield (40%). Bases such as K2CO3,
Na2CO3, NaHCO3, K3PO4, and KOt-Bu did not yield the
observed product.
(1) (a) Alonson, F.; Beletskaya, M.; Yus, I. P. Chem. Rev. 2004,
104, 3079. (b) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H.
Angew. Chem. Int. Ed. 2004, 43, 3368. (c) Trost, B. M.
Angew. Chem., Int. Ed. Engl. 1995, 34, 259. (d) Tani, K.;
Kataoka, Y. In Catalytic Heterofunctionalization; Togni, A.;
Grutzmacher, H., Eds.; Wiley-VCH: Weinheim, 2001, 171.
(e) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957.
(f) Comprehensive Handbook on Hydrosilylation;
Marciniec, B., Ed.; Pergamon Press: Oxford, 1992.
(g) Pereyre, M.; Quintard, J. P.; Rahm, A. Tin in Organic
Synthesis; Butterworth: London, 1987, .
(10) We have performed the reaction under aerobic conditions
and under inert atmosphere. In both cases the product
formation was observed but in open air a slightly better yield
was obtained. Further, using an oxygen balloon, the reaction
did not proceed. These experiments imply that the dissolved
air is essential for the product formation. At present, we have
no satisfactory explanation for this phenomenon and it
clearly needs further work.
(2) (a) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley and Sons: New York, 1994, Chap. 2.
(b) Pietrusiewicz, K. M.; Zablocka, M. Chem. Rev. 1994, 94,
1375. (c) Yamanoi, Y.; Imamoto, T. Rev. Heteroat. Chem.
1999, 20, 227. (d) Komarov, I. V.; Borner, A. Angew. Chem
Int. Ed. 2001, 40, 1197. (e) Van Leeuwen, P. W. N. M.;
Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000,
100, 2741.
(11) Typical Procedure
(3) (a) Han, L. B.; Hua, R.; Tanaka, M. Angew. Chem. Int. Ed.
1998, 37, 94. (b) Allen, A. Jr.; Ma, L.; Lin, W. Tetrahedron
Lett. 2000, 41, 152. (c) Allen, A. Jr.; Ma, L.; Lin, W.
Tetrahedron Lett. 2002, 43, 3707. (d) Mirzaei, F.; Han,
L. B.; Tanaka, M. Tetrahedron Lett. 2001, 42, 297. (e)Han,
L. B.; Mirzaei, F.; Zhao, C. Q.; Tanaka, M. J. Am Chem. Soc.
2000, 122, 5407. (f) Zhao, C. Q.; Han, L. B.; Tanaka, M.
Organometallics 2000, 19, 4196.
Secondary phosphine-borane ( )-1b (198 mg, 1.1 mmol)
and phenyl acetylene (2a, 198 mg, 1.0 mmol) were dissolved
in MeCN (5 mL). To this reaction mixture,
[Cu(OH)·TMEDA]2Cl2 (38 mg, 10 mol%) and Et3N (20 mg,
20 mol%) were added sequentially. The resulting reaction
mixture was stirred 6 h at ambient temperature. The reaction
mixture was quenched with sat. NH4Cl solution and
Synlett 2009, No. 7, 1180–1184 © Thieme Stuttgart · New York

1184
G. Kumaraswamy et al.
LETTER
mm–1, F000 = 640, T = 294 (2) K. Data collection yielded
extracted with EtOAc (2 × 10 mL) and washed with brine
solution. The combined extracts were dried over anhyd
Na2SO4 and filtered, and evaporation under reduced pressure
resulted in a crude residue. The residue was subjected to
SiO2 column chromatography, and it furnished the phenacyl
tertiary phosphine-borane 3b in 80% yield (262 mg).
1H NMR (300 MHz, CDCl3): d = 1.18 (d, J = 14.3 Hz, 9 H),
3.55–3.85 (m, 2 H), 7.36–7.53 (m, 6 H), 7.76–7.89 (m, 4
H).13C NMR (75 MHz, CDCl3): d = 25.4, 29.8, 30.1, 128.1,
128.2, 129.0, 131.3, 131.4, 133.4, 133.5, 133.6, 195.9. IR
(KBr): 2925, 2855, 2386, 1668, 1143, 1068, 996, 738 cm–1.
MS–FAB: m/z = 297 [M – 1]+. HRMS (ESI-MS): m/z calcd
for C18H24PBONa: 321.1415; found: 321.1415.
8337 reflection resulting in 3095 unique, averaged
reflection, 3041 with I > 2s(I), q range: 1.80–25.00°. Full-
matrix least-squares refinement led to a final R = 0.0293,
wR = 0.0770 and GOF = 1.013. Intensity data were
measured on Bruker Smart Apex with CCD area detector.
CCDC 714891 contains the supplementary crystallographic
data for the structure 3b. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
(13) Transformation of styrene 2i into a phenacyl tertiary
phosphine-borane 3b can be tentatively rationalized on the
basis of Wacker-type oxidation.
(12) The crystal belongs to the monoclinic crystal system, space
group is Cc with a = 11.6520 (7) Å, b = 22.6559 (14) Å,
c = 7.5701 (5) Å, b = 117.933 (1), V = 1765.58 (19) Å3,
(14) (a) Hamada, T.; Ye, X.; Stahl, S. S. J. Am. Chem. Soc. 2008,
130, 833. (b) Kumaraswamy, G.; Pitchaiah, G.;
Ram Krishna, G.; RamaKrishna, D. S.; Sadaiah, K.
Tetrahedron Lett. 2006, 47, 2013.
r
calc = 1.122 mg m–3, l = 0.71073Å, m(Mo Ka) = 0.152
Synlett 2009, No. 7, 1180–1184 © Thieme Stuttgart · New York

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