Dess-Martin Periodinane Oxidation of Alcohols in the Presence of Stabilized Phosphorus Ylides: A Convenient Method for the Homologation of Alcohols via Unstable Aldehydes

Full text of DOI:10.1021/jo971569u

9376
J . Org. Chem. 1997, 62, 9376-9378
Sch em e 1
Dess-Ma r tin P er iod in a n e Oxid a tion of
Alcoh ols in th e P r esen ce of Sta bilized
P h osp h or u s Ylid es: A Con ven ien t Meth od
for th e Hom ologa tion of Alcoh ols via
Un sta ble Ald eh yd es
Anthony G. M. Barrett,* Dieter Hamprecht, and
Mitsuru Ohkubo
Department of Chemistry, Imperial College of Science,
Technology and Medicine, London SW7 2AY, UK
Sch em e 2
Received August 22, 1997
Both FR-900848 (1)1 and U-106305 (2),2 which are
structurally remarkable polycyclopropane natural prod-
ucts noted for antifungal activities and the inhibition of
a
Reagents and conditions: (1) PhCO2H (4 equiv), 9a (4 equiv),
10 (2.4 equiv), DMSO, CH2Cl2; NaHCO3, H2O, Et2O.
Dess-Martin periodinane 10 was added to a mixture
of 2-butyne-1,4-diol (7), the ester ylide 9a , and benzoic
acid, an additive to accelerate the reaction and to enhance
the E:Z selectivity of the Wittig reaction,7 and this
smoothly provided the adduct 8 (89%) as a mixture of
trans-trans and trans-cis isomers (4:1) (Scheme 2). It is
clear that this in situ oxidation and Wittig homologation
is very convenient compared for the handling of 2-bu-
tynedial,8 a sensitive dialdehyde prepared from the acid-
mediated hydrolysis of acetal derivatives and prone to
rapid decomposition. This instability is underscored by
the fact that Dess-Martin oxidation of 2-butyne-1,4-diol
(7) and subsequent addition of the ylide 9a failed to
provide any dienyne 8 whatsoever. This oxidation/Wittig
homologation sequence was applied to further examples
(Table 1). The formation of dienediyne diester 12 and
tetraene 18 further illustrate the usefulness of the
method for the preparation and direct derivatization of
unstable aldehydes. Although the reaction of 1,2-
ethanediol (13) gave the diene diester 14 in only modest
yield (27%), direct reaction of commercial 40% aqueous
glyoxal with ylide 9a proceeded in better yield [89%,
(E,E):(E,Z) ) 2.5:1]. The preparation of diene 14 in this
way represents an improvement over existing methods.3
Oxidation/homologation of 1,3-propanediol (15) gave ethyl
(E)-2,4-pentadienoate (16) probably via elimination of
3-hydroxypropanal or an iodine(III) derivative. An at-
tempt to use the method to prepare and trap trifluoro-
acetaldehyde was unsuccessful. In this example only a
trace of diethyl fumarate (3%) was formed presumably
via oxidation of the ylide.
cholesteryl transfer proteins, respectively, have been the
subject of considerable synthetic efforts recently.3 During
the course of our studies on the structural elucidation
and total syntheses of these substances, we have repeat-
edly used a double oxidation, Wittig homologation,
DIBAl-H reduction and Charette cyclopropanation4 se-
quence to generate polycyclopropane arrays (Scheme 1).
Several of the dialdehydes in this sequence were found
to be sensitive substances and as such, the Wittig
reaction was carried out directly following oxidation.
During these studies we had occasion to examine the
Dess-Martin periodinane oxidation5 of diols in the
presence of ester ylides. This process, which is prece-
dented in the work of Huang on radiopharmaceuticals,6
is especially valuable for the generation and in situ
trapping of particularly unstable dialdehydes such as
2-butynedial and 2,4-hexadiynedial.
(1) Yoshida, M.; Ezaki, M.; Hashimoto, M.; Yamashita, M.; Shige-
matsu, N.; Okuhara, M.; Kohsaka, M.; Horikoshi, K. J . Antibiot. 1990,
43, 748.
The Dess-Martin periodinane oxidation of a mixture
of a stabilized phosphorus ylide and an alcohol should
find further use in the preparation and functionalization
of delicate aldehydes.
(2) Kuo, M. S.; Zielinski, R. J .; Cialdella, J . I.; Marschke, C. K.;
Dupuis, M.; Li, G. P.; Kloosterman, D. A.; Spilman, C. H.; Marshall,
V. P. J . Am. Chem. Soc. 1995, 117, 10629.
(3) For example see: (a) Barrett, A. G. M.; Doubleday, W. W.;
Kasdorf, K.; Tustin, G. J . J . Org. Chem. 1996, 61, 3280. (b) Barrett,
A. G. M.; Kasdorf, K. J . Chem. Soc., Chem. Commun. 1996, 325. (c)
Barrett, A. G. M.; Hamprecht, D.; White, A. J . P.; Williams, D. J . J .
Am. Chem. Soc. 1996, 118, 7863. (d) Barrett, A. G. M.; Kasdorf, K. J .
Am. Chem. Soc. 1996, 118, 11030. (e) Falck, J . R.; Mekonnen, B.; Yu,
J .; Lai, J .-Y. J . Am. Chem. Soc. 1996, 118, 6096. (f) Charette, A. B.;
Lebel, H. J . Am. Chem. Soc. 1996, 118, 10327.
Exp er im en ta l Section
Dieth yl Octa -2(E),6(E)-d ien -4-yn e-1,8-d ioa te (8) a n d Di-
eth yl Octa -2(E),6(Z)-d ien -4-yn e-1,8-d ioa te. 2-Butyne-1,4-diol
(4) Charette, A. B.; J uteau, H. J . Am. Chem. Soc. 1994, 116, 2651.
Charette, A. B.; Prescott, S.; Brochu, C. J . Org. Chem. 1995, 60, 1081.
Charette, A. B.; Marcoux, J .-F. Synlett 1995, 1197.
(5) Dess, D. B.; Martin, J . C. J . Am. Chem. Soc. 1991, 113, 7277.
(6) Huang, C. C. J . Labeled Compd. Radiopharm. 1987, 24, 675.
(7) Vedejs, E.; Peterson, M. J . Adv. Carbanion Chem. 1996, 2, 1;
Top. Stereochem. 1994, 21, 1. Barrett, A. G. M.; Hamprecht, D.; White,
A. J . P.; Williams, D. J . J . Am. Chem. Soc. 1997, 119, 8608.
(8) Gorgues, A.; Le Coq, A. Tetrahedron Lett. 1979, 4825.
S0022-3263(97)01569-7 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 26, 1997 9377
(2H, d, J ) 15.5 Hz), 6.40 (2H, d, J ) 15.5 Hz), 3.79 (6H, s); 13
Ta ble 1. Dess-Ma r tin Oxid a tion of Diols in th e
C
P r esen ce of Ylid es
NMR (75 MHz, CDCl3) δ 165.6, 133.5, 123.3, 81.2, 81.1, 52.1;
MS (CI, NH3) m/e 236 (M + NH4)+, 218 (M+•); exact mass (CI,
NH3) calcd for C12H10O4‚NH4 (M + NH4)+, 236.0923, found (M
+ NH4)+ 236.0926. (E,Z)-12: yellow solid, mp 72-73 °C (lit.9
76-78 °C); TLC Rf 0.28 (hexanes:Et2O 6:1); IR (film) 2131, 1733,
1716, 1612, 1440, 1328, 1258, 1226, 1192, 1173, 953 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 6.86 (1H, d, J ) 15.9 Hz), 6.39 (1H,
d, J ) 15.9 Hz), 6.33 (1H, d, J ) 11.5 Hz), 6.26 (1H, d, J ) 11.5
Hz), 3.81 (3H, s), 3.80 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.7,
164.5, 133.1, 132.2, 123.6, 121.4, 84.2, 82.1, 81.6, 80.7, 52.1, 51.8;
MS (CI, NH3) m/e 236 (M + NH4)+, 219 (M + H)+; exact mass
(CI, NH3) calcd for C12H10O4‚NH4 (M + NH4)+, 236.0923, found
(M + NH4)+ 236.0923.
Dieth yl h exa -2(E),4(E)-d ien e-1,6-d ioa te (14): white crys-
tals, mp 57-59 °C (pentane-Et2O) (lit.10 63-64 °C); TLC Rf 0.28
(hexanes:Et2O 3:1); IR (film) 1699, 1613, 1253, 1172, 1026, 863
cm-1 1H NMR (300 MHz, CDCl3) δ 7.26-7.34 (2H, m), 6.14-
;
6.22 (2H, m), 4.23 (4H, q, J ) 7.1 Hz), 1.30 (6H, t, J ) 7.1 Hz);
13C NMR (75 MHz, CDCl3) δ 165.9, 140.8, 128.4, 60.9, 14.2; MS
(CI, NH3) m/e 216 (M + NH4)+, 199 (M + H)+; exact mass (CI,
NH3) calcd for C10H14O4‚NH4 (M + NH4)+, 216.1236, found (M
+ NH4)+ 216.1235.
Eth yl (E)-2,4-p en ta d ien oa te (16):11 colorless oil; TLC Rf
0.47 (hexanes:Et2O 6:1); IR (film) 1723, 1299, 1260, 1155, 1036,
1
979 cm-1; H NMR (300 MHz, CDCl3) δ 7.29 (1H, dd, J ) 11.0,
15.4 Hz), 6.48 (1H, ddd, J ) 10.4, 11.0, 16.9 Hz), 5.93 (1H, d, J
) 15.4 Hz), 5.63 (1H, d, J ) 16.9 Hz), 5.50 (1H, d, J ) 10.4 Hz),
4.23 (2H, q, J ) 7.1 Hz), 1.32 (3H, t, J ) 7.1 Hz); 13C NMR (75
MHz, CDCl3) δ 166.8, 144.6, 134.7, 125.4, 122.2, 60.4, 14.2; MS
(CI, NH3) m/e 144 (M + NH4)+, 127 (M + H)+; exact mass (CI,
NH3) calcd for C7H11O2 (M + H)+, 127.0759, found (M + H)+
127.0761.
Diet h yl d eca -2(E),4(E),6(E),8(E)-t et r a en e-1,10-d ioa t e
(18): pale yellow crystals, mp 132-136 °C (from hexanes-Et2O)
(lit.12 131-132 °C); TLC Rf 0.46 (hexanes:Et2O 3:1); IR (film)
1
1704, 1628, 1012, 878 cm-1; H NMR (300 MHz, CDCl3) δ 7.33
(2H, dd, J ) 10.9, 15.3 Hz), 6.48-6.65 (4H, m), 5.97 (2H, d, J )
15.3 Hz), 4.23 (4H, q, J ) 7.1 Hz), 1.31 (6H, t, J ) 7.1 Hz); 13C
NMR (75 MHz, CDCl3) δ 166.7, 143.4, 138.9, 133.6, 123.0, 60.5,
14.3; MS (CI, NH3) m/e 268 (M + NH4)+, 251 (M + H)+; exact
mass (CI, NH3) calcd for C14H19O4 (M + H)+, 251.1283, found
(M + H)+ 251.1288.
Dieth yl octa -2(E),4(E),6(E)-tr ien e-1,8-d ioa te (20): white
crystals, mp 86-89 °C (pentane-Et2O) (lit.13 88-89 °C); TLC
Rf 0.32 (hexanes:AcOEt 6:1); IR (film) 1712, 1627, 1370, 1343,
1300, 1235, 1133, 1026, 866 cm-1; 1H NMR (300 MHz, CDCl3) δ
7.33 (2H, ddd, J ) 3.2, 7.5, 15.3 Hz), 6.64 (2H, dd, J ) 3.2, 7.5
Hz), 6.03 (2H, d, J ) 15.3 Hz), 4.23 (4H, q, J ) 7.2 Hz), 1.31
(6H, t, J ) 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 166.4, 142.7,
136.9, 124.7, 60.6, 14.3; MS (CI, NH3) m/e 242 (M + NH4)+, 225
(M + H)+, 195; exact mass (CI, NH3) calcd for C12H17O4 (M +
H)+, 225.1127, found (M + H)+ 225.1128.
(177 mg, 2.0 mmol), PhCO2H (977 mg, 8.0 mmol), and
EtO2CCHdPPh3 (9a ) (2.79 g, 8.0 mmol) were dissolved in dry
CH2Cl2 (15 mL) and dry DMSO (2.5 mL). Dess-Martin perio-
dinane (10) (2.04 g, 4.8 mmol) was added, and the mixture
turned orange-red brown within seconds and started to boil.
After 30 min at room temperature, saturated aqueous NaHCO3
solution, Et2O, and some solid NaHCO3 were added. After
stirring for 10 min, the mixture was filtered, the organic layer
was separated and concentrated in vacuo. The residue was
chromatographed on silica (hexanes:Et2O 6:1) to give 8 (318 mg,
72%) and (E,Z)-8 (79 mg, 18%) as colorless oils. 8: TLC Rf 0.41
(hexanes:Et2O 6:1); IR (film) 1716, 1626, 1312, 1265, 1175, 1164,
1
1036, 960 cm-1; H NMR (300 MHz, CDCl3) δ 6.90 (2H, d, J )
Diet h yl
oct a -2(E),4(Z),6(E)-t r ien e-1,8-d ica r b oxyla t e
(22):13 white crystals, mp 57-61 °C (pentane-Et2O); TLC Rf
15.2 Hz), 6.32 (2H, d, J ) 15.2 Hz), 4.25 (4H, q, J ) 7.1 Hz),
1.32 (6H, t, J ) 7.1 Hz); 13C NMR (75 MHz, CDCl3) δ 165.4,
132.1, 123.8, 93.9, 61.0, 14.2; MS (CI, NH3) m/e 240 (M + NH4)+,
223 (M + H)+, 193; exact mass (CI, NH3) calcd for C12H15O4 (M
+ H)+, 223.0970, found (M + H)+ 223.0972. (E,Z)-8: TLC Rf
0.34 (hexanes:Et2O 6:1); IR (film) 1715, 1621, 1304, 1178, 1031,
0.32 (hexanes:AcOEt 6:1); IR (film) 1706, 1621, 1367, 1318, 1270,
1212, 1145, 1041, 982, 887 cm-1; H NMR (300 MHz, CDCl3) δ
1
7.78-7.87 (2H, m), 6.39-6.46 (2H, m), 6.03 (2H, d, J ) 15.1 Hz),
4.26 (4H, q, J ) 7.1 Hz), 1.34 (6H, t, J ) 7.1 Hz); 13C NMR (75
MHz, CDCl3) δ 166.5, 137.6, 133.5, 125.1, 60.7, 14.3; MS (CI,
NH3) m/e 242 (M + NH4)+, 225 (M + H)+; exact mass (CI, NH3)
calcd for C12H16O4‚NH4 (M + NH4)+, 242.1392, found (M + NH4)+
242.1390.
1
960 cm-1; H NMR (300 MHz, CDCl3) δ 6.89 (1H, dd, J ) 2.7,
15.9 Hz), 6.25 (1H, d, J ) 15.9 Hz), 6.22 (1H, dd, J ) 2.7, 11.5
Hz), 6.11 (1H, d, J ) 11.5 Hz), 4.18 (2H, q, J ) 7.2 Hz), 4.15
(2H, q, J ) 7.2 Hz), 1.25 (3H, t, J ) 7.2 Hz), 1.23 (3H, t, J ) 7.2
Hz); MS (CI, NH3) m/e 240 (M + NH4)+, 223 (M + H)+, 193;
exact mass (CI, NH3) calcd for C12H15O4 (M + H)+, 223.0970,
found (M + H)+ 223.0962.
Eth yl 2(E)-p en ten -4-yn oa te (24):14 colorless oil; TLC Rf
0.57 (hexanes:Et2O 6:1); IR (film) 3293, 3263, 2105, 1719, 1306,
1
1270, 1181, 1039, 963 cm-1; H NMR (300 MHz, CDCl3) δ 6.73
(1H, dd, J ) 2.3, 15.9 Hz), 6.32 (1H, d, J ) 15.9 Hz), 4.23 (2H,
q, J ) 7.2 Hz), 3.35 (1H, d, J ) 2.3 Hz), 1.31 (3H, t, J ) 7.2 Hz);
13C NMR (75 MHz, CDCl3) δ 165.4, 132.5, 123.9, 85.8, 80.2, 60.9,
The following compounds were prepared according to the
procedure described for compounds 8 and (E,Z)-8.
Dim et h yl
d eca -2(E),8(E)-d ien e-4,6-d iyn e-1,10-d ioa t e
(12): yellow crystals, mp 104-106 °C (lit.9 105-107 °C); TLC
Rf 0.38 (hexanes:Et2O 6:1); IR (film) 2135, 1715, 1610, 1441,
(10) Moffett, L. R., J r.; Hill, W. E. J . Org. Chem. 1962, 27, 1454.
(11) Rodriguez, J .; Waegell, B. Synthesis 1988, 534.
(12) Yanovskaya, L. A.; Stepanova, R. N.; Kogan, G. A.; Kucherov,
V. F. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1963, 774.
(13) Adger, B. J .; Barrett, C.; Brennan, J .; McGuigan, P.; McKervey,
M. A.; Tarbit, B. J . Chem. Soc., Chem. Commun. 1993, 1220. Kasahara,
A.; Izumi, T.; Kudou, N. Synthesis 1988, 704.
1307, 1273, 1178, 963 cm-1; H NMR (300 MHz, CDCl3) δ 6.84
1
(9) Farrell, I. W.; Thaller, V.; Turner, J . L. J . Chem. Soc., Perkin
Trans. 1977, 1886. Marvell, E. N.; Seubert, J .; Vogt, G.; Zimmer, G.;
Moy, G.; Siegmann, J . R. Tetrahedron 1978, 34, 1323.

9378 J . Org. Chem., Vol. 62, No. 26, 1997
Notes
14.2; MS (FAB) m/e 123 (M - H)-, 95. Z-(24):14 colorless oil;
TLC Rf 0.34 (hexanes:Et2O 6:1); IR (film) 2097, 1725, 1299, 1261,
1181, 1035, 979 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.22 (1H, d,
J ) 11.6 Hz), 6.14 (1H, dd, J ) 2.4, 11.6 Hz), 4.26 (2H, q, J )
7.2 Hz), 3.63 (1H, d, J ) 2.4 Hz), 1.33 (3H, t, J ) 7.2 Hz).
pean Commission for a TMR Research Fellowship (to
D.H.), the Wolfson Foundation for establishing the
Wolfson Centre for Organic Chemistry in Medical
Science at Imperial College, the Engineering and Physi-
cal Science Research Council, the Fujisawa Phar-
maceutical Company Ltd. for support for M.O., and
G.D. Searle & Company for generous unrestricted
support.
Ack n ow led gm en t. We thank Glaxo Wellcome for
the most generous endowment (to A.G.M.B.), the Euro-
(14) Kovalev, B. G.; Yanovskaya, L. A.; Kucherov, V. F.; Kogan, G.
A. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1963, 127.
J O971569U