Synthesis of α-keto esters and amides via oxidative cleavage of cyanoketophosphoranes by dimethyldioxirane

Full text of DOI:10.1021/jo0015974

3606
J . Org. Chem. 2001, 66, 3606-3609
Sch em e 1
Sch em e 2
Sch em e 3
Syn th esis of r-Keto Ester s a n d Am id es via
Oxid a tive Clea va ge of
Cya n ok etop h osp h or a n es by
Dim eth yld ioxir a n e
Man-Kin Wong,* Chun-Wing Yu, Wai-Hung Yuen, and
Dan Yang*
Department of Chemistry, The University of Hong Kong,
Pokfulam Road, Hong Kong
yangdan@hku.hk
Received November 9, 2000
In tr od u ction
R-Keto esters and amides have been recognized as
important functional moieties for inhibitors of hydrolytic
enzymes such as serine and cysteine proteases.1 The
inhibitory activities can be attributed to the facile forma-
tion of stable tetrahedral adducts between the electro-
philic R-keto groups and nucleophilic residues at the
enzyme active sites. Development of efficient synthetic
methods for these R-keto esters and amides is thus of
great interest.2 Wasserman and co-workers devised an
efficient method for synthesizing R-keto esters and
amides via oxidative cleavage of CdP double bonds
followed by trapping with alcohols and amines, respec-
tively (Scheme 1).3 This method has been employed in
the synthesis of a variety of enzyme inhibitors such as
poststatin, eurystatin A, YM-47141, and YM-47142.4
Ozone is generally employed as the oxidant for the
cleavage reactions.5 However, for substrates bearing
sensitive functionalties, milder and more selective oxi-
dants have to be used.6
extend this efficient method to the synthesis of R-keto
esters and amides via dioxirane-mediated oxidative
cleavage of cyanoketophosphoranes and subsequent trap-
ping with nucleophiles (Scheme 2).11
Resu lts a n d Discu ssion
According to the procedure described by Wasserman
and co-workers,3a cyanoketophosphoranes 1-12 were
readily prepared by coupling of the corresponding car-
boxylic acids and (cyanomethylene)phosphorane in the
presence of EDCI (Scheme 3).12
R-Keto esters and amides were prepared by using two
slightly different protocols. For the preparation of R-keto
esters 1a -12a (Table 1, entries 1-12), dimethyldiox-
irane13 (2 equiv, 0.04-0.06 M in acetone) was added to
solutions of cyanoketophosphoranes 1-12 in MeOH. For
the preparation of R-keto amides 13a and 14a (Table 1,
Dioxiranes,7 a new class of versatile oxidants, are
known to cleave CdN8 and CdP9 double bonds under
mild reaction conditions. Indeed, Wasserman and co-
workers reported that dimethyldioxirane can substitute
for ozone in the cleavage reactions of phosphorus ylides
to afford vicinal tricarbonyl compounds while sensitive
functional groups remained intact.9b,10 In this paper, we
(1) (a) Otto, H.-H.; Schirmeister, T. Chem. Rev. 1997, 97, 133. (b)
Babine, R. E.; Bender, S. L. Chem. Rev. 1997, 97, 1359.
(7) For excellent reviews on dioxirane chemistry, see: (a) Adam, W.;
Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205. (b) Murray,
R. W. Chem. Rev. 1989, 89, 1187. (c) Curci, R. In Advances in
Oxygenated Processes; Baumstark, A. L., Ed.; J AI Press: Greenwich.
CT, 1990; Vol. 2, p 1. (d) Adam, W.; Hadjiarapoglou, L. P. In Topics in
Current Chemistry; Springer-Verlag: Berlin, 1993; Vol. 164, p 45.
(8) For the cleavage of CdN double bonds to carbonyls, see: (a)
Altamura, A.; Curci, R.; Edwards, J . O. J . Org. Chem. 1993, 58, 7289.
(b) Saba, A. Synth. Commun. 1994, 24, 695. (c) Hamilton, R.; Mckervey,
M. A.; Rafferty, M. D.; Walker, B. J . J . Chem. Soc., Chem. Commun.
1994, 37.
(9) For the cleavage of CdP double bonds, see: (a) ref 7d; (b)
Wasserman, H. H.; Baldino, C. M.; Coats, S. J . J . Org. Chem. 1995,
60, 8231.
(10) For the oxidation of R-bromo-â-dicarbonyls to vicinal tricarbo-
nyls using dimethyldioxirane and base, see: Coats, S. J .; Wasserman,
H. H. Tetrahedron Lett. 1995, 36, 7735.
(11) Wasserman and co-workers mentioned one example in which
dimethyldioxirane was used for the cleavage of an aliphatic cyanoke-
tophosphorane in MeOH to furnish the R-keto methyl ester. See: ref
9b.
(12) Detailed procedures for the preparation of cyanoketophospho-
ranes 1-12 are available in the Supporting Information.
(13) For the preparation of isolated dimethyldioxirane, see: (a)
Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847. (b) Adam,
W.; Chan, Y.-Y.; Cremer, D.; Gauss, J .; Scheutzow, D.; Schindler, M.
J . Org. Chem. 1987, 52, 2800. (c) Adam, W.; Hadjiarapoglou, L.; Smerz,
A. Chem. Ber. 1991, 124, 227.
(2) (a) Wipf, P.; Kim, H.-Y. Tetrahedron Lett. 1992, 33, 4275. (b)
Wipf, P.; Kim, H.-Y. J . Org. Chem. 1993, 58, 5592. (c) Ryu, I.;
Kuriyama, H.; Minakata, S.; Komatsu, M.; Yoon, J .-Y.; Kim, S. J . Am.
Chem. Soc. 1999, 121, 12190. For reviews on vicinal polycarbonyl
compounds, see: (d) Rubin, M. B. Chem. Rev. 1975, 75, 177. (e) Rubin,
M. B.; Gleiter, R. Chem. Rev. 2000, 100, 1121.
(3) (a) Wasserman, H. H.; Ho, W.-B. J . Org. Chem. 1994, 59, 4364.
(b) Wasserman, H. H.; Wang, J . J . Org. Chem. 1998, 63, 5581.
(4) (a) Conde-Frieboes, K.; Reynolds, L. J .; Lio, Y.-C.; Hale, M. R.;
Wasserman, H. H.; Dennis, E. A. J . Am. Chem. Soc. 1996, 118, 5519.
(b) Wasserman, H. H.; Petersen, A. K. Tetrahedron Lett. 1997, 38, 953.
(c) Wasserman, H. H.; Petersen, A. K. J . Org. Chem. 1997, 62, 8972.
(d) Wasserman, H. H.; Chen, J .-H.; Xia, M. J . Am. Chem. Soc. 1999,
121, 1401. (e) Wasserman, H. H.; Xia, M.; Petersen, A. K.; J orgensen,
M. R.; Curtis, E. A. Tetrahedron Lett. 1999, 40, 6163. (f) Paris, M.;
Pothion, C.; Michalak, C.; Martinez, J .; Fehrentz, J .-A. Tetrahedron
Lett. 1998, 39, 6889. (g) Fretz, H. Tetrahedron Lett. 1996, 37, 8475.
(5) Singlet oxygen is also effective in the cleavage reactions. See:
(a) Wasserman, H. H.; Fukuyama, J .; Murugesan, N.; Vanduzer, J .;
Lombarbo, L.; Rotello, V.; McCarthy, K. J . Am. Chem. Soc. 1989, 111,
371. (b) Wasserman, H. H.; Rotello, V. M.; Williams, D. R.; Benbow, J .
W. J . Org. Chem. 1989, 54, 2785.
(6) For the use of Oxone in the cleavage reactions, see: (a) Wasser-
man, H. H.; Vu, C. B. Tetrahedron Lett. 1990, 31, 5205. (b) Wasserman,
H. H.; Ennis, D. S.; Power, P. L.; Ross, M. J .; Gomes, B. J . Org. Chem.
1993, 58, 4785. (c) ref 4a.
10.1021/jo0015974 CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/17/2001

Notes
J . Org. Chem., Vol. 66, No. 10, 2001 3607
Ta ble 1. Oxid a tive Clea va ge of Cya n ok etop h osp h or a n es by Dim eth yld ioxir a n ea
a
Unless otherwise indicated, all reactions were carried out with cyanoketophosphoranes (0.1-0.3 mmol) in MeOH (5 mL) and a solution
of dimethyldioxirane (2 equiv) in acetone (ca. 0.04-0.06 M) at room temperature. Isolated yield after flash column chromatography.c 4a
b
d
was found to be contaminated with a trace amount of 8a coming from elimination of the acetate moiety. 5b was obtained when the
reaction was conducted in EtOH (5 mL). e -78 °C. f Reaction was performed at 0 °C with 2.4 equiv of dimethyldioxirane. g 0 °C. Reaction
h
i
was performed in CH2Cl2 (5 mL) at -78 °C with benzylamine (1 equiv) in CH2Cl2 (2 mL) as the nucleophile. Reaction was performed in
CH2Cl2 (5 mL) at -78 °C with L-leucine methyl ester (1 equiv) in CH2Cl2 (2 mL) as the nucleophile.

3608 J . Org. Chem., Vol. 66, No. 10, 2001
Notes
Sch em e 4
R-Keto amides 13a and 14a were obtained in 81 and
72% yields by oxidative cleavage of cyanoketophospho-
rane 1 at -78 °C and subsequent trapping with benzy-
lamine and L-leucine methyl ester, respectively (entries
13 and 14). However, the sterically bulky substrate 12
could not be cleaved at -78 °C even after 3 h. When the
cleavage reaction was carried out at room temperature,
the starting material disappeared in 20 min, and subse-
quent treatment of benzylamine failed to furnish the
desired keto amide. Presumably, the intermediate R,â-
diketonitrile generated after the addition of dimethyl-
dioxirane quickly decomposed at room temperature even
before benzylamine was added.
This protocol for the preparation of R-keto esters and
amides via oxidative cleavage of cyanoketophosphoranes
utilizes isolated dimethyldioxirane under mild and neu-
tral conditions. It requires short reaction time (usually
less than 5 min) and simple workup procedure. Future
work will be directed at exploring the potential of this
method in other synthetic applications.
Sch em e 5
Exp er im en ta l Section
entries 13 and 14), 1 equiv of the corresponding amine
in CH2Cl2 was added after the oxidative cleavage reaction
was complete in CH2Cl2 at -78 °C as judged by TLC
(within 5 min).
Gen er a l Meth od s. All reactions were performed in oven-
dried apparatus. Dichloromethane was distilled over calcium
hydride. Flash column chromatography was performed using the
indicated solvent system on E. Merck silica gel 60 (230-400
mesh ASTM). Dimethyldioxirane was prepared according to the
literature procedure.13
As illustrated in Table 1, unsubstituted, tert-butyloxy-,
silyloxy-, and acetoxy-substituted cyanoketophospho-
ranes 1-4 afforded the corresponding R-keto methyl
esters 1a -4a 14 in 82-89% yields (entries 1-4). However,
for oxidative cleavage of unprotected â-hydroxy cyanoke-
tophosphorane 5, a cyclic acetal 5a instead of the
anticipated R-keto ester was formed in 32% yield (entry
5). This may be due to the fact that there was a trace
amount of formaldehyde present in methanol. When the
expected R-keto ester 15 was formed, the γ-hydroxyl
group attacked formaldehyde to provide 5a as the final
product (Scheme 4). In contrast, when the reaction was
carried out in EtOH, a five-membered ring lactone 5b
was isolated in 37% yield (entry 5). It is likely that the
nucleophilic addition of ethanol to the intermediate R,â-
diketonitrile 16 was slower than that of methanol
(Scheme 4). Consequently, the hydroxyl group of 16
immediately attacked the carbonyl group adjacent to the
nitrile group intramolecularly to give the stable five-
membered ring R-ketolactone 17, which tautomerized to
the final product 5b.
Cyanoketophoshporanes 6 and 7 with electron rich aryl
rings underwent smooth cleavage to provide 6a and 7a
in 86 and 64% yield, respectively (entries 6 and 7). While
cyanoketophoshorane 8 gave 8a in 85% yield with the
conjugated double bond remained intact (entry 8), for
cyanoketophosphorane 9 with an isolated trisubstituted
double bond, the one-pot cleavage and epoxidation of 9
furnished epoxy keto ester 9a in 79% yield (entry 9). More
interestingly, when compound 10 with an γ-δ double
bond was subjected to the reaction conditions, keto ester
10a bearing an allylic alcohol moiety was obtained in 56%
yield after silica gel chromatography (entry 10). Appar-
ently, compound 10a came from the rearrangement of
epoxy keto ester 18 via enol intermediate 19 (Scheme 5).
As shown in entry 11, cyanoketophoshorane 11 gave 11a
in 87% yield with the triple bond remaining intact. For
cyanoketophosphorane 12 bearing an R-substituent, the
reaction rate was slower, and keto ester 12a was formed
in 62% yield in 20 min (entry 12).
Gen er a l P r oced u r e for Oxid a tive Clea va ge of Cya n o-
k etop h osp h or a n es 1-12 (Ta ble 1, en tr ies 1-12). To a
solution of 1 (0.10 g, 0.24 mmol) in MeOH (5 mL) was added a
solution of dimethyldioxirane in acetone (0.04 M, 12 mL, 0.48
mmol) at room temperature. After stirring for 5 min, TLC
analysis indicated the disappearance of starting materials. The
reaction mixture was concentrated, and the crude residue was
purified by flash column chromatography (20% EtOAc in n-
hexane) to afford 1a 15 (0.034 g, 82% yield) as a colorless oil.
Analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf ) 0.55;
1H NMR (300 MHz, CDCl3) δ 3.87 (s, 3H), 2.84 (t, J ) 7.3 Hz,
2H), 1.63 (m, 2H), 1.30 (m, 6H), 0.89 (t, J ) 6.8 Hz, 3H); 13C
NMR (75.48 MHz, CDCl3) δ 194.77, 161.98, 53.28, 39.71, 31.84,
28.98, 23.28, 22.82, 14.38; IR (CH2Cl2) 1732 cm-1; EIMS (20 eV)
m/z 172 (M+, 2), 113 (100), 85 (26); HRMS (EI) for C9H16O3 (M+),
calcd 172.1099, found 172.1097.
Oxid a tive Clea va ge of Cya n ok etop h osp h or a n e 1 to
r-Keto Am id e 13a (Ta ble 1, en tr y 13). To a solution of 1 (0.10
g, 0.24 mmol) in CH2Cl2 (5 mL) was added a solution of
dimethyldioxirane in acetone (0.04 M, 12 mL, 0.48 mmol) at -78
°C. After stirring for 5 min, TLC analysis indicated the disap-
pearance of starting materials. A solution of benzylamine (26
mg, 0.24 mmol) in CH2Cl2 (2 mL) was added to the reaction
mixture. After stirring for 10 min, the solvents were evaporated
off under reduced pressure. The crude residue was subjected to
flash column chromatography (5% EtOAc in n-hexane) to provide
13a (0.048 g, 81% yield) as a colorless oil. Analytical TLC (silica
gel 60), 50% EtOAc in n-hexane, Rf ) 0.76; 1H NMR (270 MHz,
CDCl3) δ 7.28-7.44 (m, 5H), 4.46 (d, J ) 6.1 Hz, 2H), 2.94 (t, J
) 7.3 Hz, 3H), 1.38-1.66 (m, 2H), 1.27-1.34 (m, 6H), 0.88 (t, J
) 6.6 Hz, 3H); 13C NMR (67.94 MHz, CDCl3) δ 199.23, 160.06,
137.06, 128.84, 127.89, 127.86, 43.41, 36.86, 31.51, 28.74, 23.18,
22.46, 14.01; IR (CH2Cl2) 3413, 1719, 1687 cm-1; EIMS (20 eV)
m/z 247 (M+, 42), 113 (100); HRMS (EI) for C15H21NO2 (M+),
calcd 247.1572, found 247.1569.
(14) It was found that 4a was prone to elimination of the acetoxy
moiety to give 8a during the purification by column chromatography.
Thus, the reaction mixture was concentrated under reduced pressure
after the disappearance of starting material 4, and the residue was
diluted with 50 mL of 20% EtOAc in n-hexane and filtered through a
short pad of silica gel to provide 4a .
(15) Yang, D.; Wong, M.-K.; Wang, X.-C.; Tang, Y.-C. J . Am. Chem.
Soc. 1998, 120, 6611.

Notes
Oxid a tive Clea va ge of Cya n ok etop h osp h or a n e 1 to
J . Org. Chem., Vol. 66, No. 10, 2001 3609
2.0 Hz, 1H), 7.11 (dd, J ) 8.4, 2.0 Hz, 1H), 6.82 (d, J ) 8.4 Hz,
1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.15 (t, J ) 7.4 Hz, 2H), 2.88 (t,
J ) 7.4 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ 192.94, 161.14,
154.45, 133.62, 133.15, 128.44, 111.99, 111.57, 56.28, 53.05,
40.95, 27.66; IR (CH2Cl2) 1734 cm-1; EIMS (20 eV) m/z 302 (M+,
47), 300 (M+, 48), 284 (12), 282 (12), 243 (23), 241 (26), 201 (95),
199 (100); HRMS (EI) for C12H13O4Br (M+), calcd 299.9997, found
299.9985.
Meth yl 4-Ben zo[1,3]d ioxol-5-yl-2-oxobu tyr a te (7a ). Ana-
lytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf ) 0.56;
as a white solid; mp 51-53 °C; 1H NMR (300 MHz, CDCl3) δ
6.63-6.74 (m, 3H), 5.92 (s, 2H), 3.86 (s, 3H), 3.14 (t, J ) 7.4 Hz,
2H), 2.88 (t, J ) 7.4 Hz, 2H); 13C NMR (67.94 MHz, CDCl3) δ
193.15, 161.23, 147.71, 146.05, 133.78, 121.20, 108.87, 108.30,
100.89, 53.01, 41.26, 28.70; IR (CH2Cl2) 1732 cm-1; EIMS (20
eV) m/z 236 (M+, 30), 177 (13), 135 (100); HRMS (EI) for
C12H12O5 (M+), calcd 236.0685, found 236.0682.
Meth yl 2-Oxoh ep t-3-en oa te (8a ). Analytical TLC (silica gel
60), 20% EtOAc in n-hexane, Rf ) 0.5; as a syrup; 1H NMR (270
MHz, CDCl3) δ 7.21 (dt, J ) 16.0, 7.0 Hz, 1H), 6.66 (dt, J )
16.0, 2.0 Hz, 1H), 3.89 (s, 3H), 2.30 (ddd, J ) 14.5, 7.5, 2.0 Hz,
2H), 1.55 (sextet, J ) 7.5 Hz, 2H), 0.96 (t, J ) 7.5 Hz, 3H); 13C
NMR (67.94 MHz, CDCl3) δ 183.01, 162.78, 155.21, 125.20,
52.87, 35.10, 21.06, 13.71; IR (CH2Cl2) 1737 cm-1; EIMS (20 eV)
m/z 156 (M+, 1), 113 (13); HRMS (EI) for C8H12O3 (M+), calcd
156.0786, found 156.0765.
r-Keto Am id e 14a (Ta ble 1, en tr y 14). A solution of L-leucine
methyl ester in CH2Cl2 was prepared by treating L-leucine
methyl ester hydrochloride salt (44 mg, 0.24 mmol), K2CO3 (0.1
g, 0.72 mmol), and two drops of H2O in CH2Cl2 (2 mL). After
stirring for 10 min, the solution was dried over anhydrous Na2-
SO4, filtered, and used for the next step. To a solution of 1 (0.10
g, 0.24 mmol) in CH2Cl2 (5 mL) was added a solution of
dimethyldioxirane in acetone (0.04 M, 12 mL, 0.48 mmol) at -78
°C. After stirring for 5 min, TLC analysis indicated the disap-
pearance of starting materials. The solution of L-leucine methyl
ester in CH2Cl2 was added to the reaction mixture. After stirring
for 10 min, the solvents were evaporated off under reduced
pressure. The crude residue was subjected to flash column
chromatography (20% EtOAc in n-hexane) to provide 14a (0.049
g, 72% yield) as a colorless oil. Analytical TLC (silica gel 60),
50% EtOAc in n-hexane, Rf ) 0.71; [R]20D ) -10.7° (c 0.42, CH2-
Cl2); 1H NMR (500 MHz, CDCl3) δ 7.27 (d, J ) 6.4 Hz, 1H), 4.56-
4.60 (m, 1H), 3.75 (s, 3H), 2.90 (t, J ) 7.0 Hz, 2H), 1.68-1.74
(m, 1H), 1.58-1.66 (m, 3H), 1.29-1.34 (m, 7H), 0.95 (d, J ) 6.2
Hz, 6H), 0.88 (t, J ) 6.8 Hz, 3H); 13C NMR (125.76 MHz, CDCl3)
δ 198.58, 172.39, 159.83, 52.48, 50.72, 41.42, 36.77, 31.51, 28.72,
24.86, 23.14, 22.77, 22.46, 21.79, 14.01; IR (CH2Cl2) 3401, 1745,
1689 cm-1; EIMS (20 eV) m/z 285 (M+, 3), 229 (26), 172 (22),
144 (100); HRMS (EI) for C15H27NO4 (M+), calcd 285.1940, found
285.1923.
Meth yl 4-ter t-Bu toxy-2-oxoh ep ta n oa te (2a ). Analytical
TLC (silica gel 60), 50% EtOAc in n-hexane, Rf ) 0.5; as a syrup;
1H NMR (300 MHz, CDCl3) δ 4.03 (quintet, J ) 5.9 Hz, 1H),
3.87 (s, 3H), 3.00 (dd, J ) 15.4, 6.4 Hz, 1H), 2.95 (dd, J ) 15.3,
5.6 Hz, 1H), 1.29-1.51 (m, 4H), 1.16 (s, 9H), 0.91 (t, J ) 7.3 Hz,
3H); 13C NMR (75.48 MHz, CDCl3) δ 193.72, 161.71, 73.98, 67.89,
52.81, 46.14, 39.28, 28.31, 18.60, 14.07; IR (KBr) 1731 cm-1; MS
(ESI) m/z 231 (M+ + 1, 10), 157 (16); HRMS (EI) for C8H13O3
(M+ - t-BuO), calcd 157.0865, found 157.0865.
Meth yl 6-(3,3-Dim eth yl-oxir a n -2-yl)-4-m eth yl-2-oxoh ex-
a n oa te (9a ). Analytical TLC (silica gel 60), 50% EtOAc in
n-hexane, Rf ) 0.66; as a syrup; H NMR (300 MHz, CDCl3) δ
1
3.87 (s, 3H), 2.86 (ddd, J ) 17.0, 6.0, 3.5 Hz, 1H), 2.66-2.74 (m,
2H), 2.12 (septet, J ) 6.6 Hz, 1H), 1.34-1.63 (m, 4H), 1.31 (s,
3H), 1.27 (d, J ) 2.0 Hz, 3H), 0.97 (d, J ) 7.0 Hz, 3H); 13C NMR
(75.47 MHz, CDCl3) δ 193.82, 161.62, 64.20, 64.16, 58.35, 58.23,
52.95, 46.26, 46.20, 33.35, 28.61, 28.59, 26.37, 26.34, 24.86, 19.63,
19.60, 18.70, 18.65; IR (KBr) 1731 cm-1; EIMS (20 eV) m/z 228
(M+, 1), 211 (13), 169 (26), 123 (100); HRMS (EI) for C12H20O4
(M+), calcd 228.1362, found 228.1357.
Meth yl 5-Hyd r oxy-2-oxoh ep t-3-en oa te (10a ). Analytical
TLC (silica gel 60), 50% EtOAc in n-hexane, Rf ) 0.8; as a syrup;
1H NMR (500 MHz, CDCl3) δ 7.18 (dd, J ) 16.0, 4.5 Hz, 1H),
6.91 (dd, J ) 16.0, 2.0 Hz, 1H), 4.35-4.39 (m, 1H), 3.90 (s, 3H),
1.61-1.74 (m, 2H), 0.10 (t, J ) 7.5 Hz, 3H); 13C NMR (125.78
MHz, CDCl3) δ 182.87, 162.37, 154.94, 123.04, 72.50, 52.96,
29.44, 9.47; IR (KBr) 3473, 1737 cm-1; EIMS (20 eV) m/z 113
(M+ - COOMe, 100); HRMS (EI) for C6H9O2 (M+ - COOMe),
calcd 113.0602, found 113.0589.
Met h yl 4-ter t-Bu t yld im et h ylsilyloxy-2-oxoh ep t a n oa t e
(3a ). Analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf
) 0.6; as a syrup; 1H NMR (300 MHz, CDCl3) δ 4.18 (quintet, J
) 5.5 Hz, 1H), 3.80 (s, 3H), 2.97 (dd, J ) 15.5, 7.1 Hz, 1H), 2.85
(dd, J ) 15.5, 5.1 Hz, 1H), 1.20-1.47 (m, 4H), 0.96 (t, J ) 7.0
Hz, 3H), 0.82 (s, 9H), 0.05 (s, 3H), 0.01 (s, 3H); 13C NMR (67.94
MHz, CDCl3) δ 193.18, 161.43, 68.65, 52.93, 46.44, 39.97, 25.75,
18.20, 17.95, 14.12, -4.52, -4.86; IR (KBr) 1732 cm-1; CIMS
m/z 289 (M+ + 1, 17), 231 (8), 201 (26), 187 (100), 159 (53); HRMS
(EI) for C10H19O4Si (M+ - t-Bu), calcd 231.1053, found 231.1058.
Meth yl 4-Acetoxy-2-oxoh ep ta n oa te (4a ). Analytical TLC
(silica gel 60), 50% EtOAc in n-hexane, Rf ) 0.5; as a syrup; 1H
NMR (300 MHz, CDCl3) δ 5.20-5.30 (m, 1H), 3.88 (s, 3H), 3.11
(dd, J ) 16.3, 4.3 Hz, 1H), 2.98 (dd, J ) 16.3, 8.0 Hz, 1H), 2.01
(s, 3H), 1.24-1.69 (m, 4H), 0.94 (t, J ) 7.4 Hz, 3H); 13C NMR
(125.76 MHz, CDCl3) δ 190.80, 170.88, 160.96, 69.93, 53.12,
44.16, 36.35, 20.96, 18.43, 13.75; IR (CH2Cl2) 1735 cm-1; CIMS
Meth yl 2-Oxon on a d ec-10-yn oa te (11a ). Analytical TLC
(silica gel 60), 30% EtOAc in n-hexane, Rf ) 0.6; as a syrup; 1H
NMR (300 MHz, CDCl3) 3.87 (s, 3H), 2.84 (t, J ) 7.2 Hz, 2H),
2.11-2.16 (m, 4H), 1.27-1.61 (m, 22H), 0.86-0.89 (m, 3H); 13
C
NMR (75.48 MHz, CDCl3) δ 194.24, 161.55, 80.32, 79.98, 52.83,
39.24, 31.81, 29.19, 29.12, 29.09, 28.99, 28.84, 28.79, 28.77, 28.53,
22.85, 22.62, 18.71, 18.66, 14.06; IR (CH2Cl2) 1733 cm-1; EIMS
(20 eV) m/z 322 (M+, 7), 263 (26); HRMS (EI) for C20H34O3 (M+),
calcd 322.2508, found 322.2512.
m/z 217 (M+ + 1, 12), 129 (18); HRMS (EI) for C7H13O2 (M+
COCOOMe), calcd 129.0916, found 129.0927.
-
Meth yl 4-Hyd r oxy-6-p r op yl-[1,3]d ioxa n e-4-ca r boxyla te
(5a ). Analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf
12a .3a Analytical TLC (silica gel 60), 50% EtOAc in n-hexane,
) 0.23; as a syrup; H NMR (300 MHz, CDCl3) δ 5.27 (d, J ) 6
Rf ) 0.36; as a syrup; [R]20 ) +24.5° (c 0.92 CH2Cl2); 1H NMR
1
D
Hz, 1H), 4.89 (d, J ) 6 Hz, 1H), 3.86-3.96 (m, 1H), 3.85 (s, 3H),
3.82 (br s, 1H), 2.12 (t, J ) 12 Hz, 2H), 1.26-1.64 (m, 5H), 0.93
(t, J ) 7.1 Hz, 3H); 13C NMR (75.48, CDCl3) δ 170.11, 93.27,
87.40, 71.91, 53.33, 37.74, 36.45, 17.95, 13.91; IR (CH2Cl2) 3501,
1763 cm-1; EIMS (20 eV) m/z 204 (M+, 6); HRMS (EI) for
C9H16O5 (M+), calcd 204.0998, found 204.0986.
3-Hyd r oxy-5-p r op yl-5H-fu r a n -2-on e (5b). Analytical TLC
(silica gel 60), 50% EtOAc in n-hexane, Rf ) 0.3; as a syrup; 1H
NMR (300 MHz, CDCl3) δ 6.47 (br s, 1H), 6.22 (d, J ) 1.9 Hz,
1H), 4.96 (m 1H), 1.30-1.80 (m, 4H), 0.97 (t, J ) 7.3 Hz, 3H);
13C NMR (75.48 MHz, CDCl3) δ 170.36, 142.03, 119.06, 79.57,
36.20, 18.22, 13.81; IR (CH2Cl2) 3502, 1763 cm-1; EIMS (20 eV)
m/z 142 (M+, 11), 125 (16); HRMS (EI) for C7H10O3 (M+), calcd
142.0630, found 142.0639.
(300 MHz, CDCl3) δ 7.27-7.31 (m, 5H), 5.12-5.20 (m, 1H), 5.02-
5.08 (m, 1H), 3.85 (s, 3H), 3.01-3.24 (m, 2H), 1.40 (s, 9H); 13C
NMR (75.48 MHz, CDCl3) δ 192.07, 160.63, 154.78, 135.01,
129.14, 128.50, 127.02, 80.25, 57.71, 53.00, 37.09, 28.15; IR (CH2-
Cl2) 3430, 1756, 1720 cm-1; MS (ESI) m/z 307 (M+, 7); HRMS
(EI) for C13H18NO2 (M+ - COCOOMe), calcd 220.1337, found
220.1331.
Ack n ow led gm en t. This work was supported by The
University of Hong Kong (URC/CRCG grant), Hong
Kong Research Grants Council, and HKU Generic Drug
Research Program.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for preparation of cyanoketophosphoranes 1-12; 1H and
13C NMR spectra of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
Met h yl 4-(3-Br om o-4-m et h oxyp h en yl)-2-oxob u t yr a t e
(6a ).16 Analytical TLC (silica gel 60), 30% EtOAc in n-hexane,
Rf ) 0.36; as a syrup; 1H NMR (300 MHz, CDCl3) δ 7.39 (d, J )
(16) Yang, D.; Wong, M.-K.; Yan, Z. J . Org. Chem. 2000, 65, 4179.
J O0015974