Bi(NO3)3.5H2O catalyzed phosphonylation of aldehydes: An efficient route to α-hydroxyphosphonates

Article abstract of DOI:10.1080/10426507.2016.1247085

The Bi(NO₃)₃.5H₂O mediated synthesis of α-hydroxyphosphonates via phosphonylation of aldehydes is reported herein. Both conventional and microwave technology was efficiently applied to range of aromatic, heteroaromatic, α,

Full text of DOI:10.1080/10426507.2016.1247085

ACCEPTED MANUSCRIPT
Bi(NO
3
)
3
.5H O catalyzed phosphonylation of aldehydes: an efficient route to α-
2
hydroxyphosphonates
a*
a
a
a
b
Anil Kumar, Shivali Jamwal, Shahaba Khan, Nasseb Singh, and Vijai K. Rai
a
Synthetic Organic Chemistry Lab., Faculty of Sciences, Shri Mata Vaishno Devi University,
Katra, Jammu & Kashmir 182 320, India.
b
Department of Chemistry, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh 495 009,
India.
*
Corresponding author: Tel. +91-941-916-6329; fax: +91-199-128-5694; e-mail:
anilsharmachemistry@gmail.com
Abstract
The Bi(NO
3
)
3
.5H O mediated synthesis of α-hydroxyphosphonates via phosphonylation of
2
aldehydes is reported herein. Both conventional and microwave technology was efficiently ap-
plied to range of aromatic, heteroaromatic, α,β-unsaturated aldehydes under solvent-free condi-
tions. The solvent free conditions, avoidance of toxic reagents and excellent yield are some of
the remarkable features of this protocol to access the medicinally privileged structure, α-
hydroxyphosphonates.
Keywords: Bismuth nitrate, microwave, phosphonylation, α-hydroxyphosphonates, solvent-free.
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Introduction
The α-hydroxyphosphonates are well recognized to show a wide range of biological ac-
1
2
3
4
tivities such as antibacterial and antifungal, antiviral, anticancer, rennin inhibitory, HIV pro-
5
6
tease, and enzyme inhibitor properties. Additionally, they are versatile intermediates in the syn-
thesis of a vast range of biologically active natural and synthetic products including un-natural
7
amino acids. The Pudovik and Abramov motivated phosphonylation of aldehydes with alkyl
8
phosphite is the most authoritative route used for synthesizing α-hydroxyphosphonates . These
transformations have been demonstrated by utilizing variety of catalytic system such as sodium
9
10
11
12
alkoxide, piperazine, EtMgBr, [(Me
3
Si)
2
N]
3
La(μ-Cl)Li(THF) , quaternary ammonium hy-
3
1
3
14
15
16
17
18
19
droxide, MgO, LDA, KCsF
2
,
guanidine hydrochloride, KH
2
PO
4
,
amberlyst-15,
2
0
21
22
23
24
25
DBU, KF/Al
2
O
3
, quinine, camphor sulfonic acid, oxalic acid, K
3
PO4, silica-supported
2
6
27
28
29
30
31
32
33
Tungstic acid, AlCl
3
or HCl/, LiClO
4
, MoO
2 2
Cl
, K
2
CO
3
, CaO, Na
2
CO
3
, Ti(O-i-Pr)
4
,
3
4
35
36
37
38
39
TMSCl, tetramethylguanidine, Et
3
N, NH
4
VO
3
, Lanthanide anilido complexes, n-BuLi,
4
0
41
organo-bi-metallic catalysts, 1,5,7-triaza bicyclo[4.4.0]dec-1-ene systems, hydroxide ion ex-
4
2
43
change-resin, sodium modified hydroxyapatite (Na-HAP), sodium-modified fluorapatite (Na-
4
4
45
FAP) etc. Recently several important reports utilizing these protocols were also reported . De-
spite great degrees of success, most of these protocols suffered from limitations such as use of
1
0,14,15,20,36
29
27
stochiometric or even more catalyst
prolonged reaction time, acidic conditions, and
2
7a
moderate yield. Consequently, developing clean, high yielding and environmentally friendly
protocol would be highly satisfying.
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Among bismuth salts, Bi(NO
3
)
3
.5H O has received considerable attention in the literature
2
and it has been elegantly used for many organic transformations such as multicomponent reac-
4
6
47
48
49
tions, synthesis of acylals, acetals, oxidation of aromatic aldehydes, oxidation of sulfides to
5
0
51
52
sulfoxides, oxidation of Hantzsch 1,4-Dihydropyridines, synthesis of pyrroles, synthesis of
5
3
54
α-amino phosphonates, guanidylation of N-benzoylthioureas and for nitration of aromatic
5
5
compounds.
5
6
In continuation of our interest towards the development of new methodologies, we report
herein a new and efficient route for the synthesis of α-hydroxyphosphonates using conventional
as well as microwave technology (Scheme 1).
Results and Discussions
In our preliminary examination, a mixture of anisaldehyde (1 mmol) and triethylphosphite (1
mmol) was stirred at room temperature in the presence of 5 mol% of Bi(NO
3
)
3
.5H O under neat
2
conditions. After 10 h the product was isolated in 60% yield by column chromatography and was
found to be diethyl (hydroxy(4-methoxyphenyl)methyl)phosphonate as revealed by comparison
57
of its physical and spectroscopic data.
Next in an effort to improve the yield, the catalyst loadings were varied. At 10 and 15 mol%
loadings (Table 1, entries 2 and 3) yield increased (90 and 91%). However, 20 mol% offered no
improvement (Table 1, entries 4). Thus, 10 mol% of catalyst was found to be optimum
concentration for the envisaged reaction. Next, different solvents were used at ambient
temperature, but the yield of product decreased to 50-78% (table 1, entries 5-9) and hence the
best conversion was observed under neat conditions, presumably due to the high concentration of
reacting species being in close proximity than when dissolved in a solvent. Next, additional
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
catalysts (SbCl
3
, p-TsOH, BiCl
3
, L-Proline) were screened but the yield decreased to 45-70%
.5H O (10 mol%) was found to be the most effective
(
table 1, entries 10-13), hence Bi(NO
3
)
3
2
catalyst for this conversion under solvent-free conditions.
Subsequently, the optimum conditions were applied to additional substrates and the results are
summarized in table 2. It is interesting to note that electron rich and electron deficient aldehydes
reacted efficiently to give the anticipated product in excellent yield. The heterocyclic aldehydes
also gave the desired product 3j-k in good yield (Table 2, entry 10 and 11) whereas the reaction
did not take place with aliphatic aldehydes to generate the desire product 3l (Table 2, entry12).
However, α, β-unsaturated aldehydes resulted the corresponding product 3i in appreciable yield
(
table 2, entry 9).
The work up procedure is very simple and no chromatographic technique was used for
purification as the desired products were purified by crystallization from ethanol. All the prod-
ucts were characterized by comparison of its physical and spectral data.
To demonstrate the generality of the present protocol similar reactions were conducted with
diethylphosphite as nucleophile and relatively low yield (54-64%) of desired product was ob-
o
tained (Table 3, entries 1-6) even at heating at 60 C. This is perhaps due to the better nucleo-
philicity of triethylphosphite in comparison to diethylphosphite owing to the availability of lone
2
7b
pair of electron on phosphorous atom.
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Taking into consideration the well documented applications of microwave technology to
5
9
improve the yield and obtain an advantage in terms of time economy, we irradiated an
o
equimolar mixture of anisaldehyde and triethyl phosphite at 70 C in MW reactor (Biotage,
Model: Initiator EXP EU 355301, 012180). It was observed that desired product was formed
much faster (10 min), however the yield obtained was comparable to that of the conventional
method. Additional substrates were screened and the results are shown in table 2 which indicated
that reaction gives comparable or even better yields than the conventional method of stirring at
room temperature in most cases. Importantly, reaction did not work with aliphatic aldehydes to
generate the desire product 3l (Table 2, entry 12) akin to that of traditional method of heating.
Lastly in order to compare the efficacy of varied catalysts for the synthesis of 3a, comparative
data are shown in Table 4 (Entries1-16) which showed that our catalyst gave either better or
equivalent yield compared to most of the reported methods. However, it is important to mention
that some catalysts (Table 4, entry 4, 8, 9, 13 14 and 16) were successful at lower catalytic
loadings especially [(Me
3
Si)
2
N]
3
La(μ-Cl)Li(THF) and organo-bi-metallic (Table 4 entry 4 and
3
1
6).
The proposed mechanism, especially for the reaction with diethylphosphite (Pudovik reaction) is
depicted in Scheme 2. It is known in the literature that crystal structure of bismuth nitrate
pentahydrate is triclinic where bismuth is co-ordinated by four water molecules and three
-
6
0
bidentate NO
3
ions
and regarding the diethylphosphite it is known to exists in two tautomeric forms (scheme 2) and
6
1
that phosphonate form (4a) is active nucleophile. Additionally, several reports on the activation
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
6
2
63
-
of diethylphosphite (Phosphonate form, 4a) using chiral Lewis acid and bifunctional catalyst
are available in the literature. In view of this we proposed that Lewis base site of catalyst (NO
)
3 3
activate the phosphonate form through hydrogen bonding which subsequently attacked the
carbonyl compound to afford the desired product. The carbonyl compound can be activated by
bimuth (III) ions or by coordinating with water molecule through hydrogen bonding in absence
of basic catalyst which is hitherto a required condition for the Pudovik reaction. However, with
triethylphosphite (Abramov reaction), the catalytic activity is believed to be due to its Lewis acid
character akin to that of the reported conditions for Abramov reaction.
Conclusion
In summary, an efficient route for the synthesis of α-hydroxyphosphonates has been devel-
oped by using Bi(NO
3
)
3
.5H O under solvent-free conditions. The easy work up procedure, use of
2
cheap and moisture tolerant catalyst, avoidance of toxic solvents and use of non conventional
energy source (MW) are some of the advantages which makes this methodology an attractive and
a valuable contribution to the existing protocols.
Experimental
All starting materials and reagents were commercially available and used without further
purification. Reactions were carried out by using microwave reactor (Biotage, Model: Initiator
EXP EU 355301, 012180, Power 400W). Melting points were determined on analab melting
1
13
31
point apparatus. H , C NMR and P spectra were recorded on a Bruker spectrometer at 400,
1
00 and 162 MHz respectively in CDCl solvent. All compounds, 3a-k are known and their
3
spectral data were in agreement with reported literature values (see Supplemental Materials).
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
General procedure for synthesis of α-hydroxyphosphonates
At room temperature: A mixture of aldehyde (1 mmol), diethylphosphite or triethylphosphite (1
mmol) and Bi(NO
3
)
3
·5H O (0.1 mmol) was stirred at room temperature under solvent-free
2
conditions for appropriate time (table 1). After completion of the reaction as monitored by TLC,
reaction mixture was cooled to obtain the crude product which was recrystallised from ethanol to
afford the desired pure product (84-93%).
Under MW irradiation: A mixture of aldehyde (1 mmol), triethylphosphite (1 mmol) and
o
Bi(NO
3
)
3
·5H
2
O (0.1 mmol) was irradiated was irradiated at 70 C in MW reactor (Biotage,
Model: Initiator EXP EU 355301, 012180) until the completion of the reaction as indicated by
TLC. After completion of the reaction, the reaction mixture was cooled at room temperature and
work up was done as above to afford the desired product (88-95%). The structure of the product
3
was confirmed by their elemental and spectral data.
Acknowledgments
We sincerely thank to UGC, New Delhi for their financial support [F. No. 39-788/2010 (SR)]
and also thankful to IIIM Jammu for providing spectra.
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
References
1
2
3
. Kategaonkar, A. H.; Pokalwar, R. U.; Sonar, S. S.; Gawali, V. U.; Shingate, B. B.; Shin-
gate, M. S. Eur. J. Med. Chem. 2010, 45, 1128-1132.
. Snoeck, R.; Holy, A.; Dewolf-Peeters, C.; Van Den Oord, J.; De Clercq, E.; Andrei, G.
Antimicrob. Agents Chemother. 2002, 46, 3356-3361.
. (a) Lee, M. V.; Fong, E. M.; Singer, F. R.; Guenett, R. S. Cancer Res. 2001, 61, 2602-
2
608. (b) Bubenik, M.; Rej, R.; Nguyen-Ba, N.; Attardo, G.; Ouellet, F.; Chan, L. Bioorg.
Med. Chem. Lett. 2002, 12, 3063-3066. (c) Clercq , E. D.; Andrei , G.; Balzarini , J.;
Hatse, S.; Liekens, S.; Naesens, L.; Neyts, J. and Snoeck, R. Nucleosides and Nucleo-
tides 1999, 18, 759-771.
4
5
. Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E. Tetrahedron Lett. 1990, 31, 5587-5590.
. Stowasser, B.; Budt, K.-H.; Jian-Qi, L.; Peyman, A.; Ruppert, D. Tetrahedron Lett. 1992,
3
3, 6625-6628.
6
. (a) Košiová, I.; Šimák, O.; Panova, N.; Buděšínský, M.; Petrova, M.; Rejman, D.;
Liboska, R.; Páv, O.; Rosenberg, I. Eur. J. Med. Chem. 2014, 74, 145-168. (b) Alder, M.;
Nicholson, J. D.; Starks, D. F.; Kane, C. T.; Cornille, F.; Hackley, B. E. J. Appl. Toxicol.
1
3
1
999, 19, S5-S11. (c) Cox, R. J.; Gibson, J. S.; Martín, B. B. M. Chem. Bio. Chem. 2002,
, 874-886. (d) Marquet, F.; Cavalier, J. F.; Verger, R.; Buono, G. Eur. J. Org. Chem.
999, 1999, 1671-1678.
7
. (a) Sobhani, S.; Tashrifi, Z. Tetrahedron. 2010, 66, 1429-1439. (b) Kafarski, P.; Lejczak,
B.; Tyka, R.; Koba, L.; Pliszczak, E.; Wieczorek, P. J. Plant Growth Regul. 1995, 14,
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
99- 203. (c) Wertheimer, F. H. Science. 1987, 235, 1173-1178. (d) Yan, B.; Spilling, C.
D. J. Org. Chem. 2004, 69, 2859-2862. (e) Yan, B.; Spilling, C. D. J. Org. Chem. 2008,
3, 5385-5396. (f) Song, Y.; Niederer, D.; Lane-Bell, P. M.; Lam, L. K. P.; Crawley, S.;
Palcic, M. M.; Pickard, M. A.; Pruess, D. L. and Vederas, J. C. J. Org. Chem. 1994, 59,
784-5793.
7
5
8
. (a) Olszewski, T. K. Synthesis 2014; 46(04): 403-429. (b) Kolodiazhnyi, O. L.; Tetrahe-
dron Asymmetry 2005, 16(20), 3295-3340. (c) Zhao, D.; Wang, R. Chem. Soc. Rev. 2012,
4
1, 2095-2108. (d) Wiemer, D. F. Tetrahedron 1997, 53(49), 16609-16644.
. (a) Abramov, V. S.; Dokl. Akad. Nauk S.S.S.R. 1954, 95, 991-994.
b) Pudovik, A. N.; Arbuzov, B. A. Dokl. Akad. Nauk S.S.S.R. 1950, 73, 327-329.
9
1
(
0. Kumar, K. S.; Reddy, C. B.; Reddy, M. V. N.; Rani, C. R. and Reddy, C. S. Org. Com-
mun. 2012, 5, 50-57.
1
1
1
1. Gawron, O.; Grelecki, C.; Reilly, W.; Sands, J. J. Am. Chem. Soc. 1953, 75, 3591-3592.
2. Wu, Q.; Zhou, J.; Yao, Z.; Xu, F. and Shen, Q. J. Org. Chem. 2010, 75, 7498-7501.
3. Alexander, C. W.; Albiniak, P. A. and Gibson, L. R. Phosphorous Sulfur Silicon Relat.
Elem. 2000, 167, 205-209.
1
1
1
1
1
4. (a) Sardarian, A. R.; Kaboudin, B. Synth. Commun. 1997, 27, 543-551.
5. Blazis, V. J.; Koeller, K. J.; Spilling, C. D. J. Org. Chem. 1995, 60, 931-940.
6. Texier-Boullet, F.; Foucaud, A. Synthesis 1982, 165-166.
7. Heydari, A.; Arefi, A.; Khaksar, S.; Tajbakhsh, M. Catal. Commun. 2006, 7, 982-984.
8. Mandhane, P. G.; Joshi, R. S.; Nagargoje, D. R.; Gill, C. H. Tetrahedron Lett. 2010, 51,
1
490-1492.
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
1
9. Tajbakhsh, M.; Heydari, A.; Khalizadeh, M. A.; Lakouraj, M. M.; Zamenian, B.;
Khaksar, S. Synlet. 2007, 15, 2347-2350.
2
2
2
0. Pamies, O.; Backvall, J. E. J. Org. Chem. 2003, 68, 4815-4818.
1. Textier-Boullet, F.; Lequitte, M. Tetrahedron Lett. 1986, 27, 3515-3516.
2. Smaardijk, A. A.; Noorda, S.; Bolhuis, F.; Wynberg, H. Tetrahedron Lett. 1985, 26, 493-
4
96.
3. Shinde, P. V.; Kategaonkar, A. H.; Shingate, B. B.; Shingare, M. S. Tetrahedron Lett.
011, 52, 2889-2892.
2
2
2
2
2
2
4. Vardat, S. M.; Baharfar, R.; Tajbakhsh, M.; Heydari, A.; Baghbanian, S. M.; Khaksar, S.
Tetrahedron Lett. 2008, 49, 6501-6504.
5. Kulkarni, M. A.; Lad, U. P.; Desai, U. V.; Mitragotri, S. D. Wadgaonkar, P. P. C. R.
Chimie 2013, 16, 148-152.
6. Santhisudha, S.; Sreelakshmi, P.; Jayaprakash, S. H.; Kumar B. V. and Reddy, C. S.
Phosphorus Sulfur Silicon Relat. Elem. 2015, 190, 1479-1488.
7. (a) Kharasch, M. S.; Mosher, R. A.; Bengelsdorf, I. S. J. Org. Chem. 1960, 25, 1000-
1
006. (b) Goldeman, W.; Soroka, M.; Wrocawska, P. Synthesis 2006, 18, 3019-3024. (c)
Congsiglio, G.; Failla, S. and Finocchiaro, P. Phosphorus Sulfur Silicon Relat. Elem.
996, 117, 37-54.
1
2
2
8. Azizi, N.; Saidi, M. R. Tetrahedron Lett. 2003, 44, 7933-7935.
9. de Noronha, R. G.; Costa, P. J.; Romao, C. C.; Calhorda, M. J. Organometallics 2009,
2
8, 6206-6212.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
3
0. Jeanmaire, T.; Hervaud, Y.; Boutevin, B. Phosphorus Sulfur Silicon Relat. Elem., 2002,
77, 1137-1145.
1
3
1. Martinez-Castro, E.; Lopez, O.; Maya, I.; Fernandez-Balanos, J. G.; Petrini, M. Green
Chem. 2010, 12, 1171-1174.
3
3
2. Keglevich, G.; Toth, V. R.; Drahos, L. Heteroatom Chem. 2011, 22, 15-17.
3. Yokomatsu, T.; Yamagishi, T.; Shibuya, S. J. Chem. Soc., Perkin Trans. I 1997, 1527-
1
534.
3
3
4. Olah, G. A.; Wu, A. J. Org. Chem. 1991, 56, 902-904.
5. Simoni, D.; Invidiata, F. P.; Manferdini, M.; Lampronti, I.; Rondanin, R.; Roberti, M.;
Pollini, G. P. Tetrahedron Lett. 1998, 39, 7615-7618.
3
3
6. Dolle, R. E.; Herpin, T. F.; Shimshock, Y. C. Tetrahedron Lett. 2001, 42, 1855-1858.
7. Sonar, S. S.; Kategaonkar, A. H.; Ware, M. N.; Gill, C. H.; Shingate, B. B.; Shingare, M.
S. Arkivoc 2009, (ii), 138-148.
3
8. Liu, C.; Qian, Q.; Nie, K.; Wang, Y.; Shen, Q.; Yuan, D. and Yao, Y. Dalton Trans.
2
014, 43, 8355-8362.
3
4
9. Liu, C.; Zhang, Y.; Qian, Q.; Yuan, D.; and Yao, Y. Org. Lett. 2014, 16, 6172-6175.
0. (a) Nie, K.; Liu, C.; Zhang, Y.; Yao, Y. J. Organomet. Chem. 2016, 804, 59-65. (b) Nie,
K.; Liu, C.; Zhang, Y. Yao, Y. Sci China Chem, 2015, 58, 1451-1460.
4
4
1. Simoni, D.; Rondanin, R.; Morini, M.; Baruchello, R.; Invidiata, F. P. Tetrahedron Lett.
2
000, 41, 1607-1610.
2. Alexander, C. W.; Albiniak, P. A.; Gibson, L. R. Phosphorus Sulfur Silicon Relat. Elem.
000, 167, 205-210.
2
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
4
4
4
3. Solhy, A.; Sebti, S.; Tahir, R.; Sebti, J.; Abba, M. O.; Bousmina, M.; Vaudreuil, S. and
Zahouilyd, M. Curr. Org. Chem. 2010, 14, 1517-1522.
4. Ramananarivo, H. R.; Solhy, A.; Sebti, J.; Smahi, A.; Zahouily, M.; Clark, J.; Sebti, S.
Sustainable Chem. Eng. 2013, 1, 403-409.
5. (a) Yakovenko, M. V.; Udilova, N. Yu.; Glukhova, T. A.; Cherkasov, A.V.; G. K. Fu-
kin, G. K.; Trifonov, A. A. New J. Chem. 2015, 39, 1083-1093. (b) Santacroce, Veroni-
ca.; Paris, E.; Cauzzi, D.; Maggi, D.; Maestri, G. E. J. Org. Chem. 2016, (3), 463–466. (c)
Xu, F.; Liu, Y.; Tu, J.; Lei, C.; Li, G.; Tetrahedron Asymmetry 2015, 26, 891-896. (d)
Muthupandi, P.; Sekar, G. Org. Biomol. Chem. 2012,10, 5347-5352. (e) Rajeshwaran, G.
G.; Nandakumar, M.; Sureshbabu, R.; Mohanakrishnan A. K. Org. Lett., 2011, 13 (6),
1
270–1273. (f) Raju, P.; Rajeshwaran, G. G.; Nandakumar, M.; Mohanakrishnan, A. K.
E. J. Org. Chem. 2015, 3513–3523.
4
4
6. Brahmachari, G.; Das, S. Tetrahedron Lett. 2012, 53, 1479-1484.
7. Aggen, D. H.; Arnold, J. N.; Hayes, P. D.; Smoter, N. J.; Mohan, R. S. Tetrahedron 2004,
6
0, 3675-3679.
4
4
5
5
5
8. Srivastava, N.; Dasgupta, S. K.; Banik, B. K. Tetrahedron Lett. 2003, 44, 1191-1193.
9. Mukhopadhyay, C.; Dutta, A. Catal. Commun. 2008, 9, 2588-2592.
0. Mashraqui, S.; Mudaliar, C.; Karnik, M. Synth. Commun. 1998, 28, 939-943.
1. Mashraqui, S. H.; Karnik, M. A. Synthesis. 1998, (5), 713-714.
2. Banik, B. K.; Banik, I.; Renteria, M.; Dasgupta, S. K. Tetrahedron Lett. 2005, 46, 2643-
2
645.
5
3. Bhattacharya, A. K.; Kaur, T. Synlett. 2007, 5, 0745-0748.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
5
5
5
4. Cunha, S.; De Lima, B. R.; de Souza, A. R. Tetrahedron Lett. 2002, 43, 49-52.
5. Samajdar, S.; Becker, F. F.; Banik, B. K. Tetrahedron Lett. 2000, 41, 8017-8020.
6. (a) Kumar, A.; Kumar, S.; Kapoor, K. K. Aust. J. Chem. 2007, 60, 621-623. (b) Rai, V.
K.; Tiku, P.; Kumar, A. Synth. Commun. 2012, 42, 1489-1499. (c) Rai, V. K.; Rai, P. K.;
Bajaj, S.; Kumar, A. Green Chem. 2011, 13, 1217-1223. (d) Rai, V. K.; Sharma, R.; Ku-
mar, A. Tetrahedron Lett. 2013, 54, 1071-1075. (e) Rai, V. K.; Sharma, N.; Kumar, A.
Synlett. 2013, 24, 0097-0101. (f) Kour, P.; Kumar, A.; Rai, V. K. Comptes Rendus
Chimie 2016, doi.org/10.1016/j.crci.2016.05.013.
5
5
7. Sardarian, A. R.; Kaboudin, B. Synth. Commun. 1997, 27, 543-551.
8. Pokalwar, R. U.; Hangarge, R. V.; Maske, P. V.; Shingare, M.S. Arkivoc 2006, (xi), 196-
2
04.
5
9. (a) Gedye, R.; Smith, F.; Westaway, K.; Ali, H.; Baldisera, L.; Laberge, L.; Rousell, J.
Tetrahedron Lett. 1986, 27, 279-282. (b) Giguere, R. J.; Bray, T. L.; Duncan, S. M.;
Majetich, G. Tetrahedron Lett.1986, 27, 4945-4948. (c) Yermolayev, S. A., Gorobets, N.
Y.; Desenko,S. M. J. Comb. Chem. 2009, 11, 44-46. (d) Li, K. -T.; Lin, Y. -B.; Yang, D.
-
Y. Org. Lett. 2014, 14, 1190-1193. (e) Naresh, G.; Kant, R.; Narender, T. Org. Lett.
014, 16, 4528-4531. (f) Manjappa, K. B.; Jhang, W. -F.; Huang, S.-Y.; Yang, D.-Y.
2
Org. Lett. 2014, 16, 5690-5693.
6
6
0. Lazarini, F. Acta Crystallogr., 1985, C41, 1144–1145.
1. (a) Kosolapoff, G.M.; Maier, L. Organic Phosphorus Compounds; John Wiley and Sons:
New York, 1973; vol. 5. (b) Mastrykukova, T. A.; Aladzheva, I. M.; Lemont’eva, I. V.;
Petrovski, P. V.; Fedin, E. I.; Kabachnik, M. I. Pure Appl. Chem. 1980, 52, 945.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
6
2. (a) Yokomatsu, T.; Yamagishi, T.; Shibuya, S. Tetrahedron Asymmetry 1993, 4, 1779-
782. (b) Groger, H.; Saida, Y.; Arai, S.; Martens, J.; Sasai, H.; Shibasaki, M.
1
Tetrahedron Lett. 1996, 37, 9291-9292. (c) Saito, B.; Egami, H.; Katsuki, T. J. Am.
Chem. Soc. 2007, 129, 1978-1986.
6
3. Rai, V.; Namboothiri, I. N. N. Tetrahedron Asymmetry, 2008, 19, 2335-2338.
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Table 1. Optimization of catalysts and reaction conditions
b
Entry Catalyst (mol%)
Solvent (mL) Time (h) Yield (%)
1
2
3
4
5
6
7
8
9
Bi(NO
3
)
3
.5H
2
O (5)
Neat
5
5
5
5
5
5
5
5
5
60
90
91
90
65
68
60
50
78
Bi(NO ) .5H O (10) Neat
3
3
2
Bi(NO
Bi(NO
Bi(NO
Bi(NO
Bi(NO
Bi(NO
Bi(NO
3
)
)
)
)
)
)
)
3
3
3
3
3
3
3
.5H
2
O (15) Neat
O (20) Neat
3
3
3
3
3
3
.5H
.5H
.5H
.5H
.5H
.5H
2
2
2
2
2
2
O (10) CH
O (10) CHCl
O (10) CH Cl
3
CN
3
2
2
O (10) Toluene
O (10) Ethanol
1
1
1
1
0
1
2
3
SbCl
p-TsOH (10)
BiCl (10)
L-Proline (10)
3
(10)
Neat
Neat
Neat
Neat
5
5
5
5
70
68
69
45
3
a
Reactions conditions: 1 (1 mmol), 2 (1 mmol) were stirred at room temperature.
b
Yield of isolated and purified product 3a.
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Table 2: Substrate scope under optimized conditions
b
ο
Entry
R
Time
MW
Yield (%)
Melting point ( C)
Stirring
h)
5
Stirring
90
MW
91
Observed Literature
(
(min)
10
5
7
1
2
119-120
120-121
5
7
6
12
89
90
67
67-68
5
7
3
4
5
5
15
15
90
92
89
94
75-76
93-94
75-77
5
7,37
94-95
2
7c
5
6
7
5
6
5
10
15
15
93
88
89
95
90
89
180-181
85
180-182
86-87
57
5
7
123
80-81
5
7
8
9
5
5
6
6
15
10
15
15
88
86
86
84
89
91
89
88
73-75
74-75
5
7
104
105-106
5
8
7
1
1
0
1
124-125
145-147
124-126
3
146-148
c
1
2
10
15
No
NA
-
-
reaction
a
Reactions were carried out by taking 1 (1 mmol), 2 (1 mmol) and Bi(NO
3
)
3
.5H O (0.1 mmol).
2
b
Yield of isolated and purified product.
c
Not applicable
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Table 3. Synthesis of α-hydroxyphosphonates using diethylphosphite
b
c
c
Entry
R
Time (h)
Yield (%)
1
2
3
4
5
6
4-MeOC
6
H
4
6
6
6
6
6
6
62
64
63
58
59
54
4-ClC
6
H
4
C
6
H
5
4-MeC
4-OHC
2-NO
6
H
4
6
H
4
2
C
6
H
4
a
Reactions were carried out by taking 1a-f (1 mmol), 4 (1 mmol) and Bi(NO
3
)
3
.5H O (10
2
o
mol%) at 60 C.
b
Time required for completion of the reaction (monitored by TLC).
c
Yield of isolated and purified product.
17
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
a
Table 4. Comparative data of Bi(NO
3
)
3
. 5H O with earlier reported catalysts for 3a.
2
Entry Catalyst (g/mol%)
Phosphite Time
Yield %
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
Bi (NO
Bi (NO
3
3
)
)
3
. 5H
. 5H
2
2
O (10)
O (10)
2
2
4
4
4
4
2
4
2
2
4
4
4
4
4
4
5 hr
10 min 91
1 min
5 min
1 hr
90
b
3
4
1
1
1
3
2
1
2
2
4
0
7
9
8
Na-FAP (1g)
[(Me Si) N] La(μ-Cl)Li(THF)
MgO (100)
Piperazine (100)
83
96
95
88
3
2
3
3
(0.1)
6 min
NH
MoO
KH PO
4
VO
3
(10)
(5)
25 min 80
18 hr
6 min
12 min 85
5 min
12 h
4 min
5 min
5 min
5 min
2
Cl
2
70
80
2
4
(5)
c
23
0
1
2
3
4
5
6
Camphor sulfonic acid
Na-HAP (1g)
4
3
2
3
3
4
1
5
5
8
9
0
85
60
96
99
99
99
Tetramethylguanidine (2 drops)
PO (5)
K
3
4
Lanthanide anilido complexes (1)
n-Butyl Lithium (10)
organo-bi-metallic catalysts (0.1)
a
Reactions were carried out by taking 1 mmol of each of anisaldehyde and tri-
ethylphosphite with 0.1
mmol of Bi(NO
3
)
3
.5H O.
2
b
o
reaction carried out at 70 C under microwave heating.
c
reaction carried out by ultrasonication.
18
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Scheme 1 Synthesis of α-hydroxyphosphonates
19
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
20
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
21
ACCEPTED MANUSCRIPT