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The first synthesis of β-amino phosphonates using cyclic sulfamidates
Tetrahedron Letters 52 (2011) 3496–3498
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
The first synthesis of b-amino phosphonates using cyclic sulfamidates q Biswanath Das ⇑, Cheruku Ravindra Reddy, Siddavatam Nagendra, Maram Lingaiah Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e
i n f o
Article history: Received 3 February 2011 Revised 28 April 2011 Accepted 29 April 2011 Available online 6 May 2011
a b s t r a c t Cyclic sulfamidates (prepared from a-amino acids and b-amino alcohols) have been used for the first time for the synthesis of novel b-amino phosphonates (chiral and achiral) by treatment with dialkyl phosphites using sodium hydride. 2-Substituted and 1,2-disubtituted b-amino phosphonates have efficiently been prepared following this method. The products are formed in high yield (79–84%) within 8–12 h. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: b-Amino phophonate Cyclic sulfamidate Dialkyl phosphite Chiral and achiral products
b-Amino phosphonic acid and its derivatives possess various important medicinal properties including anti-bacterial, enzyme inhibition, and anti-HIV activities.1 Some of these compounds have been identified as natural products.2 The parent acid was first isolated from Celiata protozoa3 and subsequently the compound along with its different derivatives was obtained from various other organisms.4 These compounds have opened a new area of biochemistry.5 The other important use of these compounds is as pesticides.6 They have also been applied in the preparation of valuable metal complexes.7 Thus the synthesis of b-amino phosphonic acid derivatives is an attractive target to the organic chemists and some methods have been developed for the preparation of these compounds.8 However, to our knowledge, b-amino phosphonates have not yet been prepared using cyclic sulfamidates. In recent years, cyclic sulfamidates have been used as an important precursor for the synthesis of a wide range of bioactive compounds.9 These compounds can easily be prepared in chiral and achiral forms and can conveniently be cleaved with nucleophiles. In continuation of our work10 on the construction of phosphonate derivatives having an amine moiety we have now prepared several cyclic sulfamidates and utilized them for the synthesis of b-amino phosphonates. The cyclic sulfamidates were prepared from different a-amino acids (1) (Scheme 1). The latter were reduced with NaBH4–I211 to afford the amino alcohol 2 which were converted into the corresponding Boc-derivatives 3 by treatment with Boc2O in Et3N. Compounds 3 were subsequently treated with SOCl2 in Et3N in the presence of imidazole to form the cyclic sulfamidites (4).12 These sulfamidites (4) were then oxidized with NaIO4 and q
Part 221 in the series ‘Studies on novel synthetic methodologies’. ⇑ Corresponding author. Tel./fax: +91 40 27160512. E-mail address: [email protected] (B. Das).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.04.115
RuCl33H2O to form the corresponding sulfamidates (5).12 The sulfamidates (5) were prepared from the a-amino acids, glycine (Table 1, entries a and b), alanine (entry c), 2-phenyl glycine (entries d and e), leucine (entries f and g), and phenyl alanine (entries h and i). Two b-amino alcohols, (R)-2-amino-3, 3-dimethyl butane-1-ol, and (2R, 3R)-methyl-2-amino-3-hydroxybanoate were also used to prepare the sulfamidates (5) (entry j for the first and entries k and l for the second) following the similar sequence of reactions as described above (Scheme 1). The prepared cyclic sulfamidates (5) were treated with dialkyl phosphites using NaH in THF under reflux to furnish b-amino phosphonates (6) (Scheme 2).
H2N R
O 1
H2N
a
OH
R
OH
2
b
OH
Boc NH
R'
R
3 R' c
O O Boc
N R
O S O 5
R'
d
Boc
S N R
O 4
R'
Scheme 1. Synthesis of cyclic sulfamidates (5) from a-amino acids (1). Reagents and conditions: (a) NaBH4, I2, THF, 70 °C, 18–22 h 93–97%; (b) (Boc)2O, Et3N, DCM, 2 h, rt; 95–98%; (c) SOCl2, Et3N, Imidazole, DCM, 2 h, 0 °C, rt, 63–69%; (d) RuCl33H2O, NaIO4, CH3CN, 0 °C, 6 h, 91–96%.
3497
B. Das et al. / Tetrahedron Letters 52 (2011) 3496–3498 Table 1 Synthesis of b-amino phosphonates 6a Entry
Sulfamidate (5)
a
Boc
b
Boc
Boc
c
d
N
O O S
N
Productb (6)
Boc
O
Boc
O
O O S
g
NH
Boc
Boc N
9.5
82
9
81
Boc O
O P
NH
8
84
12
81
10
83
11.5
79
8.5
82
9.0
81
11
80
9.5
82
OEt OEt
Ph Boc NH
O O Boc N S O
Boc NH
N
O O S
Boc NH
MeOOC
OEt
O P
OMe OMe
Boc NH
O P
OEt OEt
Ph
N
Boc NH
O
O S
O P
OMe OMe
O
Boc
NH
O P
OMe OMe
MeOOC
MeOOC
l
O P
Ph
O
Boc
OMe
OEt
O
O O S
Boc
O P
OMe
O O Boc N S O
j
c
80
OMe OMe
O O Boc N S O
Boc N
b
O P
NH
Ph
a
9.5
OMe
P
OMe
Ph
k
79
Ph O O S
h
i
OEt
P O
O O Boc N S O
Boc
11
OMe
NH
Boc
O
Ph
f
OMe
Yieldc (%)
OEt
Ph
e
O P O
O O S
N
NH
Time (h)
N
O O S
O
Boc
NH
O P
OEt OEt
MeOOC
Reaction conditions: cyclic sulfamidate (1 mmol), dialkyl phosphites (1.2 mmol), NaH (1.3 mmol), 65 °C. The structures of the products were established from their spectral (IR, 1H and 13C NMR, ESI–MS) data. Isolated yields after purification.
Various b-amino phosphonates were prepared from 5 following the above method (Table 1). The reaction was complete within 8– 12 h and the products were formed in high yield (79–84%). Both chiral and achiral b-amino phosphonates were efficiently prepared. The conversion afforded the products equally with dimethyl and diethyl phosphites. The prepared phosphonates contained alkyl,
aryl, as well as benzyl group at the b- position. The structures of the products were established from their spectral (IR, 1H, and 13C NMR and MS) and analytical data.13 In conclusion, we have developed an efficient method for the synthesis of novel b-amino phosphonates using cyclic sulfamidates for the first time. The method is suitable to generate the products
3498
B. Das et al. / Tetrahedron Letters 52 (2011) 3496–3498
O
O Boc
N
S O
R
R' 5
HP(O)(OR'')3 NaH THF, 650C 8-12 h
Boc NH
O
OR'' P
OR''
R R' 79-84 % 6
Scheme 2. Synthesis of b-amino phosphonates (6) from cyclic sulfamidates(5).
in both chiral and achiral forms. The Boc group of the products can be deprotected and the resulting amino compounds can be utilized for the preparation of their derivatives. Acknowledgments The authors thank the UGC and CSIR, New Delhi for financial assistance. References and notes 1. (a) Allen, J. G.; Arthenton, F. R.; Hall, M. J.; Hassall, C. H.; Holmes, S. W.; Lambert, R. W.; Nisbet, L. J.; Ringrose, R. S. Nature 1978, 272, 56; (b) Smith, W. W.; Bartlett, P. A. J. Am. Chem. Soc. 1998, 120, 4622; (c) Alonso, E.; Alenso, E.; Solis, A.; Del Pozo, C. Synlett 2000, 698. 2. Fields, S. C. Tetrahedron 1999, 55, 12237. 3. Horiguchi, M.; Kandatsu, M. Nature 1959, 184, 901. 4. (a) Hammerschmidt, F. Liebigs Ann. Chem. 1988, 531; (b) Hammerschmidt, F.; Vollenkle, H. Liebigs Ann. Chem. 1989, 577. 5. (a) Kittredge, J. S.; Isbell, A. F.; Huges, R. R. Biochemistry 1967, 6, 289; (b) Korn, E. D.; Dearborn, D. G.; Fales, H. M.; Sokoloski, E. D. J. Biol. Chem. 1973, 248, 2257. 6. Eto, M. Organophophopates Pesticide: Organic and Biological Chemistry; CRC Press: Cleveland, OH, 1977. 7. Caseiola, M.; Castantino, W.; Peraio, A.; Rega, T. Solid State Ionics 1995, 77, 229. 8. (a) Yuan, C.; Li, S.; Li, C.; Chen, S.; Huang, W.; Wang, G.; Pan, C.; Zhang, Y. Pure Appl. Chem. 1996, 68, 907; (b) Palacios, F.; Alonso, C.; de los Santos, J. M. Chem. Rev. 2005, 105, 899; (c) Grishkun, E. V.; Kolodyazhnyi, O. I. Russ. J. Gen. Chem. 2009, 79, 2705. 9. (a) Melendez, R. E.; Lubell, W. D. Tetrahedron 2003, 59, 2581; (b) Bower, J. F.; Rujirawanich, J.; Gallagher, T. T. Org. Biomol. Chem. 2010, 8, 1505. 10. (a) Das, B.; Balasubramanyam, P.; Krishnaiah, M.; Veeranjaneyulu, B.; Reddy, G. C. J. Org. Chem. 2009, 74, 4393; (b) Das, B.; Damodar, K.; Bhunia, N. J. Org. Chem. 2009, 74, 5607; (c) Das, B.; Satyalakshmi, G.; Suneel, K.; Damodar, K. J. Org. Chem. 2009, 74, 8400. 11. Mckennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. J. Org. Chem. 1993, 58, 3568. 12. Baldwin, J. E.; Spivey, A. C.; Schofield, C. J. Tetrahedron: Asymmetry 1990, 1, 881. 13. General experimental procedure for the preparation of b-amino phosphonates: To a solution of NaH (1.3 mmol) in THF (5 mL) dialkyl phosphite (1.2 mmol) was added and the mixture was stirred at 0 °C for 10 min. Sulfamidate (1.0 mmol) was added to the mixture which was again stirred at 65 °C. The reaction was monitored by TLC. After completion, the reaction was quenched with ice and a
mixture of EtOAc and water (1:1, 10 mL) was added. The organic layer was separated and concentrated. The residue was subjected to column chromatography (silica gel, hexane–EtOAc) to obtain a pure b-amino phosphonate. The spectral and analytical data of some representative products are given below: tert-Butyl 2-(methoxyphophono)-ethylcarbamate (6a): IR: 3429, 1689, 1518, 1457, 1369, 1252 cm1; 1H NMR (200 MHz, CDCl3): d 5.05 (1H, br s), 3.74 (6H, d, J = 10.0 Hz), 3.43–3.33 (2H, m), 2.08–1.98 (2H, m), 1.43 (9H, s); 13C NMR (50 MHz, CDCl3): d 155.2, 79.1, 51.0, (d, J = 6.5 Hz), 45.1, 31.1 (d, J = 140.0 Hz), 28.3; ESI–MS: m/z 254 [M+H]+. Anal. Calcd for C9H20NO5P: C, 42. 69; H, 7.91; N, 5.53%. Found: C, 42.75; H, 7. 87; N, 5.57%. tert-Butyl-(S)-1-(methoxyphosphono)-propan-2-carbamate (6c): ½a22 D = +7.87 (c = 0.5, CHCl3); IR: 3445, 1692, 1512, 1457, 1320, 1261 cm1; 1H NMR (200 MHz, CDCl3): d 4.84 (1H, br s), 4.02 (1H, m), 3.79 (6H, d, J = 10.0 Hz), 2.29 (1H, m), 2.02 (1H, m), 1.43 (9H, s), 1.33 (3H, d, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 154.8, 79.4, 52.1, (d, J = 6.5 Hz), 48.2, 31.0 (d, J = 140 Hz), 28.2, 21.1; ESI–MS: m/z 268 [M+H]+. Anal. Calcd for C10H22NO5P: C, 44. 94; H, 8.24; N, 5.24%. Found: C, 44.82; H, 8.30; N, 5.29%. tert-Butyl-(R)-1-(ethoxyphosphono)-4-methylpentan-2-ylcarbamate (6g): 1 ½a22 D = -20.3 (c = 0.8, CHCl3); IR: 3422, 1691, 1522, 1466, 1367, 1248 cm ; 1 H NMR (200 MHz, CDCl3): d 5.14 (1H, br s), 4.20–3.91 (5H, m), 2.25 (1H, m), 2. 02 (1H, m), 1.75–1.61 (3H, m), 1.42 (9H, s), 1.32 (6H, t, J = 7.0 Hz), 0.92 (6H, d, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 155.2, 79.0, 68.0 (d, J = 6.5 Hz), 48.6, 40.5, 30.9 (d, J = 140.0 Hz), 28.3, 24.8, 23.1, 16.2; ESI–MS: m/z 338 [M+H]+. Anal. Calcd for C15H32NO5P: C, 53.41; H, 9.50; N, 4.15%. Found: C, 53.49; H, 9.58; N, 4.12%. tert-Butyl-(R)-1-(methoxyphosphono)-3-phenylpropan-2-ylcarbamate (6h): 1 ½a25 D = -9.54 (c = 0.5, CHCl3); IR: 3422, 1688, 1505, 1455, 1367, 1249 cm ; 1 H NMR (200 MHz, CDCl3): d 7.33–7.15 (5H, m), 5.12 (1H, br s), 3.99 (1H, m), 3.72 (6H, d, J = 10.0 Hz), 3.00 (1H, m), 2.88 (1H, m), 2.28 (1H, m), 1.97 (1H, m), 1.48 (9H, s); 13C NMR (50 MHz, CDCl3): d 151.9, 137.9, 129.6, 128.5, 126.3, 79.6, 52.2 (d, J = 6.5 Hz), 48.9, 41.3, 30.9 (d, J = 140.0 Hz), 28.4; ESI–MS: m/z 344 [M+H]+. Anal. Calcd for C16H26NO5P: C, 55.98; H, 7.58; N, 4.08%. Found: C, 55.83; H, 7. 52; N, 4.12%. tert-Butyl-(R)-1-(methoxyphophono)-3-phenylpropan-2-ylcarbamate (6i): 1 ½a22 D = -8.45 (c = 0.5, CHCl3); IR: 3444, 1688, 1637, 1501, 1454, 1248 cm ; 1 H NMR (200 MHz, CDCl3): d 7.29–7.05 (5H, m), 5.21 (1H, br s), 4.30–3.98 (5H, m), 2.99 (1H, m), 2.85 (1H, m), 2.23 (1H, m), 2.01 (1H, m 1.40 (9H, s), 1.24 (6H, t, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 152.8, 139.0, 129.0, 128.3, 127.1, 78.7, 68.0 (d, J = 6.5 Hz), 46.8, 41.2, 31.9 (d, J = 140.0 Hz), 28.8, 14.5; ESI–MS: m/ z 372 [M+H]+. Anal. Calcd for C18H30NO5P: C, 58.22; H, 8.09; N, 3.77%. Found: C, 58.29; H, 8.12; N, 3.73%. tert-Butyl-(R)-1-(methoxyphosphono)-3,3-dimethylbutane-2-ylcarbamate (6j): 1 1 ½a22 D = -6.76 (c = 0.5, CHCl3); IR: 3427, 1689, 1520, 1468, 1252 cm ; H NMR (200 MHz, CDCl3): d 4.87 (1H, br s),3.82 (6H, d, J = 10.0 Hz), 4.03 (1H, m), 2.27 (1H, m), 2.02 (1H, m), 1.45 (9H, s), 1.11 (9H, s); 13C NMR (50 MHz, CDCl3): d 154.2, 79.3, 52.2 (d, J = 6.5 Hz), 48.0, 34.1, 30.8 (d, J = 140.0 Hz), 28.4, 24.5; ESI– MS: m/z 310 [M+H]+. Anal. Calcd for C13H28NO5P: C, 50.49; H, 7.06; N, 4.53%. Found: C, 50.58; H, 7.11; N, 4.49%. (2R,3S)-Methyl-2-(tert-butoxycarbonylamino)-3-(ethoxyphosphono)-butanoate (6l): ½a25 D = +5.67 (c = 0.5, CHCl3); IR: 3452, 1736, 1623, 1483, 1363, 1247 cm1; 1H NMR (200 MHz, CDCl3): d 9.74 (1H, br s), 4.32 (1H, m), 3.85 (3H, s), 4.15–3.99 (4H, m), 2.01 (1H, m), 1.68 (3H, d, J = 7.0 Hz), 1.44 (9H, s), 1.35 (6H, t, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 164.2, 151.2, 80.9, 68.6 (d, J = 6.5 Hz), 52.1, 45.8, 31.0 (d, J = 140.0 Hz), 28.6, 14.2, 12.3; ESI–MS: m/z 354 [M+H]+. Anal. Calcd for C14H28NO7P: C, 47.59; H, 7.93; N, 3.97%. Found: C, 47.48; H, 7.97; N, 3.92%.
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
The first synthesis of b-amino phosphonates using cyclic sulfamidates q Biswanath Das ⇑, Cheruku Ravindra Reddy, Siddavatam Nagendra, Maram Lingaiah Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e
i n f o
Article history: Received 3 February 2011 Revised 28 April 2011 Accepted 29 April 2011 Available online 6 May 2011
a b s t r a c t Cyclic sulfamidates (prepared from a-amino acids and b-amino alcohols) have been used for the first time for the synthesis of novel b-amino phosphonates (chiral and achiral) by treatment with dialkyl phosphites using sodium hydride. 2-Substituted and 1,2-disubtituted b-amino phosphonates have efficiently been prepared following this method. The products are formed in high yield (79–84%) within 8–12 h. Ó 2011 Elsevier Ltd. All rights reserved.
Keywords: b-Amino phophonate Cyclic sulfamidate Dialkyl phosphite Chiral and achiral products
b-Amino phosphonic acid and its derivatives possess various important medicinal properties including anti-bacterial, enzyme inhibition, and anti-HIV activities.1 Some of these compounds have been identified as natural products.2 The parent acid was first isolated from Celiata protozoa3 and subsequently the compound along with its different derivatives was obtained from various other organisms.4 These compounds have opened a new area of biochemistry.5 The other important use of these compounds is as pesticides.6 They have also been applied in the preparation of valuable metal complexes.7 Thus the synthesis of b-amino phosphonic acid derivatives is an attractive target to the organic chemists and some methods have been developed for the preparation of these compounds.8 However, to our knowledge, b-amino phosphonates have not yet been prepared using cyclic sulfamidates. In recent years, cyclic sulfamidates have been used as an important precursor for the synthesis of a wide range of bioactive compounds.9 These compounds can easily be prepared in chiral and achiral forms and can conveniently be cleaved with nucleophiles. In continuation of our work10 on the construction of phosphonate derivatives having an amine moiety we have now prepared several cyclic sulfamidates and utilized them for the synthesis of b-amino phosphonates. The cyclic sulfamidates were prepared from different a-amino acids (1) (Scheme 1). The latter were reduced with NaBH4–I211 to afford the amino alcohol 2 which were converted into the corresponding Boc-derivatives 3 by treatment with Boc2O in Et3N. Compounds 3 were subsequently treated with SOCl2 in Et3N in the presence of imidazole to form the cyclic sulfamidites (4).12 These sulfamidites (4) were then oxidized with NaIO4 and q
Part 221 in the series ‘Studies on novel synthetic methodologies’. ⇑ Corresponding author. Tel./fax: +91 40 27160512. E-mail address: [email protected] (B. Das).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.04.115
RuCl33H2O to form the corresponding sulfamidates (5).12 The sulfamidates (5) were prepared from the a-amino acids, glycine (Table 1, entries a and b), alanine (entry c), 2-phenyl glycine (entries d and e), leucine (entries f and g), and phenyl alanine (entries h and i). Two b-amino alcohols, (R)-2-amino-3, 3-dimethyl butane-1-ol, and (2R, 3R)-methyl-2-amino-3-hydroxybanoate were also used to prepare the sulfamidates (5) (entry j for the first and entries k and l for the second) following the similar sequence of reactions as described above (Scheme 1). The prepared cyclic sulfamidates (5) were treated with dialkyl phosphites using NaH in THF under reflux to furnish b-amino phosphonates (6) (Scheme 2).
H2N R
O 1
H2N
a
OH
R
OH
2
b
OH
Boc NH
R'
R
3 R' c
O O Boc
N R
O S O 5
R'
d
Boc
S N R
O 4
R'
Scheme 1. Synthesis of cyclic sulfamidates (5) from a-amino acids (1). Reagents and conditions: (a) NaBH4, I2, THF, 70 °C, 18–22 h 93–97%; (b) (Boc)2O, Et3N, DCM, 2 h, rt; 95–98%; (c) SOCl2, Et3N, Imidazole, DCM, 2 h, 0 °C, rt, 63–69%; (d) RuCl33H2O, NaIO4, CH3CN, 0 °C, 6 h, 91–96%.
3497
B. Das et al. / Tetrahedron Letters 52 (2011) 3496–3498 Table 1 Synthesis of b-amino phosphonates 6a Entry
Sulfamidate (5)
a
Boc
b
Boc
Boc
c
d
N
O O S
N
Productb (6)
Boc
O
Boc
O
O O S
g
NH
Boc
Boc N
9.5
82
9
81
Boc O
O P
NH
8
84
12
81
10
83
11.5
79
8.5
82
9.0
81
11
80
9.5
82
OEt OEt
Ph Boc NH
O O Boc N S O
Boc NH
N
O O S
Boc NH
MeOOC
OEt
O P
OMe OMe
Boc NH
O P
OEt OEt
Ph
N
Boc NH
O
O S
O P
OMe OMe
O
Boc
NH
O P
OMe OMe
MeOOC
MeOOC
l
O P
Ph
O
Boc
OMe
OEt
O
O O S
Boc
O P
OMe
O O Boc N S O
j
c
80
OMe OMe
O O Boc N S O
Boc N
b
O P
NH
Ph
a
9.5
OMe
P
OMe
Ph
k
79
Ph O O S
h
i
OEt
P O
O O Boc N S O
Boc
11
OMe
NH
Boc
O
Ph
f
OMe
Yieldc (%)
OEt
Ph
e
O P O
O O S
N
NH
Time (h)
N
O O S
O
Boc
NH
O P
OEt OEt
MeOOC
Reaction conditions: cyclic sulfamidate (1 mmol), dialkyl phosphites (1.2 mmol), NaH (1.3 mmol), 65 °C. The structures of the products were established from their spectral (IR, 1H and 13C NMR, ESI–MS) data. Isolated yields after purification.
Various b-amino phosphonates were prepared from 5 following the above method (Table 1). The reaction was complete within 8– 12 h and the products were formed in high yield (79–84%). Both chiral and achiral b-amino phosphonates were efficiently prepared. The conversion afforded the products equally with dimethyl and diethyl phosphites. The prepared phosphonates contained alkyl,
aryl, as well as benzyl group at the b- position. The structures of the products were established from their spectral (IR, 1H, and 13C NMR and MS) and analytical data.13 In conclusion, we have developed an efficient method for the synthesis of novel b-amino phosphonates using cyclic sulfamidates for the first time. The method is suitable to generate the products
3498
B. Das et al. / Tetrahedron Letters 52 (2011) 3496–3498
O
O Boc
N
S O
R
R' 5
HP(O)(OR'')3 NaH THF, 650C 8-12 h
Boc NH
O
OR'' P
OR''
R R' 79-84 % 6
Scheme 2. Synthesis of b-amino phosphonates (6) from cyclic sulfamidates(5).
in both chiral and achiral forms. The Boc group of the products can be deprotected and the resulting amino compounds can be utilized for the preparation of their derivatives. Acknowledgments The authors thank the UGC and CSIR, New Delhi for financial assistance. References and notes 1. (a) Allen, J. G.; Arthenton, F. R.; Hall, M. J.; Hassall, C. H.; Holmes, S. W.; Lambert, R. W.; Nisbet, L. J.; Ringrose, R. S. Nature 1978, 272, 56; (b) Smith, W. W.; Bartlett, P. A. J. Am. Chem. Soc. 1998, 120, 4622; (c) Alonso, E.; Alenso, E.; Solis, A.; Del Pozo, C. Synlett 2000, 698. 2. Fields, S. C. Tetrahedron 1999, 55, 12237. 3. Horiguchi, M.; Kandatsu, M. Nature 1959, 184, 901. 4. (a) Hammerschmidt, F. Liebigs Ann. Chem. 1988, 531; (b) Hammerschmidt, F.; Vollenkle, H. Liebigs Ann. Chem. 1989, 577. 5. (a) Kittredge, J. S.; Isbell, A. F.; Huges, R. R. Biochemistry 1967, 6, 289; (b) Korn, E. D.; Dearborn, D. G.; Fales, H. M.; Sokoloski, E. D. J. Biol. Chem. 1973, 248, 2257. 6. Eto, M. Organophophopates Pesticide: Organic and Biological Chemistry; CRC Press: Cleveland, OH, 1977. 7. Caseiola, M.; Castantino, W.; Peraio, A.; Rega, T. Solid State Ionics 1995, 77, 229. 8. (a) Yuan, C.; Li, S.; Li, C.; Chen, S.; Huang, W.; Wang, G.; Pan, C.; Zhang, Y. Pure Appl. Chem. 1996, 68, 907; (b) Palacios, F.; Alonso, C.; de los Santos, J. M. Chem. Rev. 2005, 105, 899; (c) Grishkun, E. V.; Kolodyazhnyi, O. I. Russ. J. Gen. Chem. 2009, 79, 2705. 9. (a) Melendez, R. E.; Lubell, W. D. Tetrahedron 2003, 59, 2581; (b) Bower, J. F.; Rujirawanich, J.; Gallagher, T. T. Org. Biomol. Chem. 2010, 8, 1505. 10. (a) Das, B.; Balasubramanyam, P.; Krishnaiah, M.; Veeranjaneyulu, B.; Reddy, G. C. J. Org. Chem. 2009, 74, 4393; (b) Das, B.; Damodar, K.; Bhunia, N. J. Org. Chem. 2009, 74, 5607; (c) Das, B.; Satyalakshmi, G.; Suneel, K.; Damodar, K. J. Org. Chem. 2009, 74, 8400. 11. Mckennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. J. Org. Chem. 1993, 58, 3568. 12. Baldwin, J. E.; Spivey, A. C.; Schofield, C. J. Tetrahedron: Asymmetry 1990, 1, 881. 13. General experimental procedure for the preparation of b-amino phosphonates: To a solution of NaH (1.3 mmol) in THF (5 mL) dialkyl phosphite (1.2 mmol) was added and the mixture was stirred at 0 °C for 10 min. Sulfamidate (1.0 mmol) was added to the mixture which was again stirred at 65 °C. The reaction was monitored by TLC. After completion, the reaction was quenched with ice and a
mixture of EtOAc and water (1:1, 10 mL) was added. The organic layer was separated and concentrated. The residue was subjected to column chromatography (silica gel, hexane–EtOAc) to obtain a pure b-amino phosphonate. The spectral and analytical data of some representative products are given below: tert-Butyl 2-(methoxyphophono)-ethylcarbamate (6a): IR: 3429, 1689, 1518, 1457, 1369, 1252 cm1; 1H NMR (200 MHz, CDCl3): d 5.05 (1H, br s), 3.74 (6H, d, J = 10.0 Hz), 3.43–3.33 (2H, m), 2.08–1.98 (2H, m), 1.43 (9H, s); 13C NMR (50 MHz, CDCl3): d 155.2, 79.1, 51.0, (d, J = 6.5 Hz), 45.1, 31.1 (d, J = 140.0 Hz), 28.3; ESI–MS: m/z 254 [M+H]+. Anal. Calcd for C9H20NO5P: C, 42. 69; H, 7.91; N, 5.53%. Found: C, 42.75; H, 7. 87; N, 5.57%. tert-Butyl-(S)-1-(methoxyphosphono)-propan-2-carbamate (6c): ½a22 D = +7.87 (c = 0.5, CHCl3); IR: 3445, 1692, 1512, 1457, 1320, 1261 cm1; 1H NMR (200 MHz, CDCl3): d 4.84 (1H, br s), 4.02 (1H, m), 3.79 (6H, d, J = 10.0 Hz), 2.29 (1H, m), 2.02 (1H, m), 1.43 (9H, s), 1.33 (3H, d, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 154.8, 79.4, 52.1, (d, J = 6.5 Hz), 48.2, 31.0 (d, J = 140 Hz), 28.2, 21.1; ESI–MS: m/z 268 [M+H]+. Anal. Calcd for C10H22NO5P: C, 44. 94; H, 8.24; N, 5.24%. Found: C, 44.82; H, 8.30; N, 5.29%. tert-Butyl-(R)-1-(ethoxyphosphono)-4-methylpentan-2-ylcarbamate (6g): 1 ½a22 D = -20.3 (c = 0.8, CHCl3); IR: 3422, 1691, 1522, 1466, 1367, 1248 cm ; 1 H NMR (200 MHz, CDCl3): d 5.14 (1H, br s), 4.20–3.91 (5H, m), 2.25 (1H, m), 2. 02 (1H, m), 1.75–1.61 (3H, m), 1.42 (9H, s), 1.32 (6H, t, J = 7.0 Hz), 0.92 (6H, d, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 155.2, 79.0, 68.0 (d, J = 6.5 Hz), 48.6, 40.5, 30.9 (d, J = 140.0 Hz), 28.3, 24.8, 23.1, 16.2; ESI–MS: m/z 338 [M+H]+. Anal. Calcd for C15H32NO5P: C, 53.41; H, 9.50; N, 4.15%. Found: C, 53.49; H, 9.58; N, 4.12%. tert-Butyl-(R)-1-(methoxyphosphono)-3-phenylpropan-2-ylcarbamate (6h): 1 ½a25 D = -9.54 (c = 0.5, CHCl3); IR: 3422, 1688, 1505, 1455, 1367, 1249 cm ; 1 H NMR (200 MHz, CDCl3): d 7.33–7.15 (5H, m), 5.12 (1H, br s), 3.99 (1H, m), 3.72 (6H, d, J = 10.0 Hz), 3.00 (1H, m), 2.88 (1H, m), 2.28 (1H, m), 1.97 (1H, m), 1.48 (9H, s); 13C NMR (50 MHz, CDCl3): d 151.9, 137.9, 129.6, 128.5, 126.3, 79.6, 52.2 (d, J = 6.5 Hz), 48.9, 41.3, 30.9 (d, J = 140.0 Hz), 28.4; ESI–MS: m/z 344 [M+H]+. Anal. Calcd for C16H26NO5P: C, 55.98; H, 7.58; N, 4.08%. Found: C, 55.83; H, 7. 52; N, 4.12%. tert-Butyl-(R)-1-(methoxyphophono)-3-phenylpropan-2-ylcarbamate (6i): 1 ½a22 D = -8.45 (c = 0.5, CHCl3); IR: 3444, 1688, 1637, 1501, 1454, 1248 cm ; 1 H NMR (200 MHz, CDCl3): d 7.29–7.05 (5H, m), 5.21 (1H, br s), 4.30–3.98 (5H, m), 2.99 (1H, m), 2.85 (1H, m), 2.23 (1H, m), 2.01 (1H, m 1.40 (9H, s), 1.24 (6H, t, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 152.8, 139.0, 129.0, 128.3, 127.1, 78.7, 68.0 (d, J = 6.5 Hz), 46.8, 41.2, 31.9 (d, J = 140.0 Hz), 28.8, 14.5; ESI–MS: m/ z 372 [M+H]+. Anal. Calcd for C18H30NO5P: C, 58.22; H, 8.09; N, 3.77%. Found: C, 58.29; H, 8.12; N, 3.73%. tert-Butyl-(R)-1-(methoxyphosphono)-3,3-dimethylbutane-2-ylcarbamate (6j): 1 1 ½a22 D = -6.76 (c = 0.5, CHCl3); IR: 3427, 1689, 1520, 1468, 1252 cm ; H NMR (200 MHz, CDCl3): d 4.87 (1H, br s),3.82 (6H, d, J = 10.0 Hz), 4.03 (1H, m), 2.27 (1H, m), 2.02 (1H, m), 1.45 (9H, s), 1.11 (9H, s); 13C NMR (50 MHz, CDCl3): d 154.2, 79.3, 52.2 (d, J = 6.5 Hz), 48.0, 34.1, 30.8 (d, J = 140.0 Hz), 28.4, 24.5; ESI– MS: m/z 310 [M+H]+. Anal. Calcd for C13H28NO5P: C, 50.49; H, 7.06; N, 4.53%. Found: C, 50.58; H, 7.11; N, 4.49%. (2R,3S)-Methyl-2-(tert-butoxycarbonylamino)-3-(ethoxyphosphono)-butanoate (6l): ½a25 D = +5.67 (c = 0.5, CHCl3); IR: 3452, 1736, 1623, 1483, 1363, 1247 cm1; 1H NMR (200 MHz, CDCl3): d 9.74 (1H, br s), 4.32 (1H, m), 3.85 (3H, s), 4.15–3.99 (4H, m), 2.01 (1H, m), 1.68 (3H, d, J = 7.0 Hz), 1.44 (9H, s), 1.35 (6H, t, J = 7.0 Hz); 13C NMR (50 MHz, CDCl3): d 164.2, 151.2, 80.9, 68.6 (d, J = 6.5 Hz), 52.1, 45.8, 31.0 (d, J = 140.0 Hz), 28.6, 14.2, 12.3; ESI–MS: m/z 354 [M+H]+. Anal. Calcd for C14H28NO7P: C, 47.59; H, 7.93; N, 3.97%. Found: C, 47.48; H, 7.97; N, 3.92%.