Novel preparation of orthoquinol acetates and their application in oxygen heterocyclization reactions

Full text of DOI:10.1021/jo9817669

J . Org. Chem. 1998, 63, 9597-9600
9597
Sch em e 1
Novel P r ep a r a tion of Or th oqu in ol Aceta tes
a n d Th eir Ap p lica tion in Oxygen
Heter ocycliza tion Rea ction s
Ste´phane Quideau,* Laurent Pouyse´gu, and
Matthew A. Looney
Department of Chemistry and Biochemistry, Texas Tech
University, Lubbock, Texas 79409-1061
Received August 31, 1998
Orthoquinone monoketals (1), i.e., 6,6-dioxocyclohexa-
2,4-dienones, are underutilized synthons in organic chem-
istry despite their considerable synthetic potential.1 Most
successful synthetic applications are usually limited to
utilizing their dienone moiety as either a dienic2,3 or a
dienophilic3a-c,4 component in [4π+2π] cycloaddition reac-
tions. A few other applications in natural product syn-
thesis have been reported,5 but further systematic ex-
ploitations of the electrophilic reactivity and differentially
activated double bonds of these orthoquinonoid species
are sporadic.6 A program aimed at exploring other
avenues for the utilization of these species in organic
synthesis has been initiated. One possibility is to exploit
the reactivity of adequately functionalized orthoquinone
monoketals in intramolecular nucleophilic addition reac-
tions to construct polyoxygenated carbocycle-fused het-
erocyclic systems, which are found in many bioactive
natural products and synthetic drugs. Conceptually,
monoketal synthons of type 3 bearing protected hetero-
atomic appendages of varied length can be prepared from
dearomatization of phenols 2 by two-electron oxidation
in the presence of an oxygen-based trapping species.
Deprotection will unmask the appended heteroatom
which could then attack the electrophilic ketal moiety to
form phenol-fused heterocycles of various sizes, such as
5, via in situ aromatization of transient enolates 4
(Scheme 1). These intramolecular 1,4-additions (i.e.,
attack at C-3 of 3) would follow an Exo-Trig cyclization
pathway. According to Baldwin’s rules, 5-Exo-Trig nu-
cleophilic ring closures are preferred to 5-Endo-Trig
closures (i.e., 1,6-addition at C-5 of 3), but both pathways
may compete for 6- and 7-membered ring closures.7 Steric
congestion at C-5 adjacent to the tetrahedral C-6 ketal
center could however favor ring closure at C-3 of 3. We
report here a novel and convenient method for the
preparation of relatively stable orthoquinone monoketals
3 and their regiocontrolled conversion into benzannulated
5- to 7-membered ether rings 5 (n ) 1-3, X ) O).
Phenols 2a -e were prepared from commercially avail-
able 2-methoxyphenols (see Supporting Information).
Silyl protective groups were chosen in anticipation of
inducing the heterocyclization event by desilylation
(Scheme 1, 3 f 5; P ) TBDPS, TBDMS, TES).8 Two-
electron oxidizing systems commonly used today to
generate orthoquinone monoketals from 2-methoxyphe-
nols are PhI(O2CCF3)2 or PhI(OAc)2 in MeOH (oxidative
methoxylation)2,3a-f and Pb(OAc)4 in AcOH or CH2Cl2
(Wessely oxidative acetoxylation).9 Oxidative methoxy-
lation furnishes 6,6-dimethoxycyclohexa-2,4-dienone de-
rivatives (e.g., 1, R1, R2 ) Me). These ketals are particu-
larly sensitive to Diels-Alder dimerization in situ unless
the system bears either relatively bulky substitutent(s)
at the 3- or 5-position3g,10 or a bromine at the 4-position.2
However, we observed that a 6-acetoxy-6-methoxycyclo-
hexa-2,4-dienone derivative, a so-called orthoquinol ac-
etate (i.e., 1, R1 ) Me, R2 ) Ac), did not dimerize in
contrast to its 6,6-dimethoxy counterpart (see Supporting
Information). On the basis of this result, phenols 2a -e
were systematically converted into orthoquinol acetates
3a -e (Scheme 1, R2 ) Ac); this was initially accomplished
by performing the Wessely oxidative acetoxylation in
CH2Cl2.9 These orthoquinone monoketal variants do not
bear any substituent at their 3- or 5-position, but do not
dimerize in situ, and are stable enough to be extracted
from the reaction mixture. We then found that the use
of PhI(OAc)2 in CH2Cl2 also led to the formation of stable
3a -e in quasi-quantitative yields (see Table 1). The
(1) Swenton, J . S. Chemistry of quinone bis- and monoketals. In The
Chemistry of Quinonoid Compounds; Patai, S., Rappoport, Z., Eds.;
Wiley: New York, 1988; Vol. 2, pp 899-962.
(2) Lai, C.-H.; Shen, Y.-L.; Liao, C.-C. Synlett 1997, 1351-1352.
(3) (a) Carlini, R.; Higgs, K.; Rodrigo, R.; Taylor, N. Chem. Commun.
1998, 65-66. (b) Carlini, R.; Higgs, K.; Older, C.; Randhawa, S. J . Org.
Chem. 1997, 62, 2330-2331. (c) Hsiu, P.-Y.; Liao, C.-C. Chem.
Commun. 1997, 1085-1086. (d) Chu, C.-S.; Lee, T.-H.; Liao, C.-C.
Synlett 1994, 635-636. (e) Hwang, J .-T.; Liao, C.-C. Tetrahedron Lett.
1991, 32, 6583-6586. (f) Liao, C.-C.; Wei, C.-P. Tetrahedron Lett. 1989,
30, 2255-2256. (g) Andersson, G. Acta Chem. Scand. 1976, B30, 403-
406. (h) Deslonchamps, P. Pure Appl. Chem. 1977, 49, 1329-1359.
(4) Coleman, R. S.; Grant, E. B. J . Am. Chem. Soc. 1995, 117,
10889-10904.
(5) (a) Churcher, I.; Hallet, D.; Magnus, P. J . Am. Chem. Soc. 1998,
120, 3518-3519. (b) Banwell, M. G.; Ireland, N. K. Chem. Commun.
1994, 591-592. (c) Yamamura, S.; Shizuri, Y.; Shigemori, H.; Okuno,
Y.; Ohkubo, M. Tetrahedron 1991, 47, 635-644. (d) Gammill, R. B.
Tetrahedron Lett. 1985, 26, 1385-1388.
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(b) Feldman, K. S. J . Org. Chem. 1997, 62, 4983-4990.
(7) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734-736,
736-738, 738-741.
(8) Variation in the choice of the silyl protecting group was due to
incompatibilities caused by the lack of reactivity of the silylating
reagents used, â-elimination of the silyloxy group, or difficulties in
achieving TBAF-mediated desilylation (see Supporting Information).
(9) (a) Wessely, F.; Swoboda, J .; Guth, V. Monatsh. Chem. 1964, 95,
649-670. (b) Bubb, W. A.; Sternhell, S. Tetrahedron Lett. 1970, 51,
4499-4502. (c) Hunter, N. R.; Plourde, G. Synth. Commun. 1986, 16,
1233-1237.
(10) Andersson, G. Acta Chem. Scand. 1976, B30, 64-70.
10.1021/jo9817669 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/21/1998

9598 J . Org. Chem., Vol. 63, No. 25, 1998
Notes
Ta ble 1. P r ep a r a tion of Or th oqu in ol Aceta tes a n d Th eir
Oxygen Heter ocycliza tion s
cessful regioselective formation of 5c is particularly
interesting, for the same methodology can be tailored to
novel approaches to the synthesis of numerous benzopy-
ran-containing13 natural products, notably including
marine shikimate-sesquiterpenoids. These natural prod-
ucts, exemplified by puupehenone,14 are currently the
focus of a renewed synthetic interest because of their
potent biological activities.15 Orthoquinone monoketals
can serve as precursors of their vicinally dioxygenated
shikimate moieties, and constitute ideal synthons for
annulation of their terpenoid units to their shikimate
units. The feasibility of this approach was demonstrated
by subjecting phenol 2d to the oxidation-cyclization
conditions (Table 1). This two-step sequence gave the
shikimate-terpenoid model compound 5d again as the
sole cyclized regioisomer in 36% yield (not optimized)
from 2d .
Orthoquinol acetate 3e was used to test the feasibility
of generating benzannulated seven-membered ether rings.
A method based on ring-closing metathesis has recently
been reported to provide a solution to this challenging
synthetic endeavor.16 Here, we hoped that the rearoma-
tization event would help overcome the energetically
disfavored direct closure of these medium-sized rings.17
The TBAF-mediated desilylation of 3e, performed at
room temperature for 1h, gave rise to the Exo-Trig
cyclized benzoxepin 5e in 20% yield. No other cyclized
regioisomers were observed; the other main products
were some recovered 2e derived from in situ reduction
of 3e, and its desilylated counterpart. Thus, optimization
of this reaction by varying the reaction time and the
nature of the silyl group may offer an efficient alternative
to the formation of phenolic benzoxepin compounds.
In summary, this preliminary study has demonstrated
the synthetic utility and potential of orthoquinol acetates
in oxygen heterocyclization chemistry. These relatively
stable orthoquinone monoketal variants are easily pre-
pared from PhI(OAc)2-mediated oxidation of 2-methoxy-
phenols. This protocol constitutes a convenient alterna-
tive to the lead salt-based Wessely oxidation. The com-
bined oxidation-cyclization of silyloxy derivatives of
functionalized 2-methoxyphenols into benzannulated 5-
to 7-membered ether rings, as described therein, should
find valuable applications in organic synthesis. The
application of this promising two-step methodology to the
synthesis of marine shikimate-sesquiterpenoids, and its
extension to nitrogen nucleophilic ring closures for the
a
b
1.0 equiv. Best results were obtained by adding a 12 mM
solution of the orthoquinol acetate to a 30 mM solution of TBAF
(2.0 equiv) in dry THF.
advantages of using PhI(OAc)2 instead of Pb(OAc)4 are
the absence of toxic lead salts, and the convenient
removal of PhI and residual AcOH byproducts by drying
under vacuum; no purification by silica gel chromatog-
raphy was necessary. Compounds 3a -e can be stored as
dry oils for several days at -20 °C without any noticeable
degradation.
Heterocyclizations are then induced upon fluoride-
mediated desilylation of 3a -e using TBAF in THF (Table
1). As expected, cyclization and concomitant rearomati-
zation via elimination of the acetoxy groups of ketals 3a
and 3b furnished the 5-Exo-Trig cyclized benzofurans
products 5a and 5b in good yields.11 Ketal 3c furnished
the 6-Exo-Trig cyclized product 5c as the sole regioisomer
in 89% optimized yield. No 6-Endo-Trig cyclized products
were observed. The regiochemistry is readily determined
by the observation of two aromatic singlets in the 1H
NMR spectrum. The cyclic connectivity was further
confirmed by the detection of a diagnostic three-bond
response between the 6-carbon and the γ-protons of 5c
in its long-range C-H correlation spectrum.12 This suc-
(12) (a) Reynolds, W. F.; Enriquez, R. G.; Escobar, L. I.; Lozoya, X.
Can J . Chem 1984, 62, 2421-2425. (b) Ralph, J . Holzforschung 1988,
42, 273-275.
(13) Phenolic benzopyrans have also been recognized as structural
units critical to the potency of synthetic dopamine agonists: Neira-
beyeh, M. A.; Reynaud, D.; Podona, T.; Ou, L.; Perdicakis, C.; Coudert,
G.; Guillaumet, G.; Pichat, L.; Gharib, A.; Sarda, N. Eur. J . Med. Chem.
1991, 26, 497-504.
(14) (a) Urban, S.; Capon, R. J . J . Nat. Prod. 1996, 59, 900-901.
(b) Ravi, B. N.; Perzanowski, H. P.; Ross, R. A.; Erdman, T. R.; Scheuer,
P. J .; Finer, A.; Clardy, J . Pure Appl. Chem. 1979, 51, 1893-1900. (c)
Hamann, M. T.; Scheuer, P. J .; Kelly-Borges, M. J . Org. Chem. 1993,
58, 6565-6569. (d) Nasu, S. S.; Yeung, B. K. S.; Hamann, M. T.;
Scheuer, P. J .; Kelly-Borges, M.; Goins, K. J . Org. Chem. 1995, 60,
7290-7292.
(15) (a) Barrero, A. F.; Alvarez-Manzaneda, E. J .; Herrador, M. M.;
Valdivia, M. V.; Chahboun, R. Tetrahedron Lett. 1998, 39, 2425-2428.
(b) Barrero, A. F.; Alvarez-Manzaneda, E. J .; Chahboun, R. Tetrahe-
dron Lett. 1997, 38, 2325-2328. (c) Arjona, O.; Garranzo, M.; Mahugo,
J .; Maroto, E.; Plumet, J .; Sa´ez, B. Tetrahedron Lett. 1997, 38, 7249-
7252.
(11) For recent examples of alternative approaches to hydroxy- and
alkoxy-substituted benzofurans, see: (a) Nova´k, L.; Kova´cs, P.; Pirok,
G.; Kolonits, P.; Hanania, M.; Dona´th, K.; Sza´ntay, C. Tetrahedron
1997, 53, 9789-9798. (b) Engler, T. A.; Gfesser, G. A.; Draney, B. W.
J . Org. Chem. 1995, 60, 3700-3706.
(16) Stefinovic, M.; Snieckus, V. J . Org. Chem. 1998, 63, 2808-2809.
(17) (a) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95-
102. (b) Dudev, T.; Lim, C. J . Am. Chem. Soc. 1998, 120, 4450-4458.

Notes
J . Org. Chem., Vol. 63, No. 25, 1998 9599
H-5), 6.75 (dd, J ) 2.1, 10.0 Hz, 1H, H-6), 7.33-7.65 (m, 10H, 2
× Ph); 13C NMR (CDCl3) δ 191.8, 169.4, 142.7, 138.4, 135.5,
133.7, 129.6, 128.9, 127.6, 125.7, 93.0, 62.5, 51.2, 31.3, 30.6, 26.8,
20.5, 19.2; EIMS m/z (relative intensity) 479 (MH+, 19), 421 (59),
419 (49), 401 (79), 343 (100). Anal. Calcd for C28H34O5Si: C,
70.26; H, 7.17. Found: C, 70.17; H, 6.95.
Or th oqu in ol a ceta te 3d . Yellow oil: Pb(OAc)4 w 99%. IR
(NaCl) 1742, 1689 cm-1; 1H NMR (CDCl3) δ 0.45-0.67 (m, 12H,
6xCH2), 0.87-0.98 (m, 18H, 6xCH3), 1.13-1.62 (m, 18H), 1.23
(s, 3H, Me), 1.24 (s, 3H, Me), 1.93-2.06 (m, 2H), 2.07 (s, 6H, 2
× AcO), 2.52-2.58 (m, 2H), 3.43 (s, 3H, MeO), 3.44 (s, 3H, MeO),
5.86 (bs, 1H, H-2), 5.88 (bs, 1H, H-2), 6.07 (d, J ) 10.0 Hz, 1H,
H-5), 6.09 (d, J ) 10.0 Hz, 1H, H-5), 6.71-6.76 (m, 2H, 2 × H-6);
13C NMR (CDCl3) δ 191.9, 169.4, 169.2, 143.0, 142.8, 138.2,
130.1, 125.6, 93.2, 93.0, 73.8, 51.3, 46.0, 45.9, 40.7, 35.7, 28.8,
26.7, 26.3, 25.7, 25.6, 21.9, 21.8, 20.6, 7.2, 7.0, 6.9, 6.8; CIMS
m/z (relative intensity) 423 (MH+, 10), 422 (M+, 13), 363 (73),
291 (100); HRMS (CI) calcd for C23H38O5Si 422.2488, found
422.2477.
synthesis of lycorine-type Amaryllidaceae alkaloids are
in progress.
Exp er im en ta l Section
Gen er a l. Tetrahydrofuran (THF) and diethyl ether (Et2O)
were purified by distillation from sodium/benzophenone under
Ar immediately before use. EtOAc and CH2Cl2 were distilled
from CaH2 prior to use. Light petroleum refers to the fraction
boiling in the 40-60 °C range. Moisture and oxygen sensitive
reactions were carried out in flame-dried glassware under Ar.
Evaporations were conducted under reduced pressure at tem-
peratures less than 45 °C unless otherwise noted. Column
chromatography was carried out under positive pressure using
32-63 µm silica gel (Bodman) and the indicated solvents.
Melting points are uncorrected. One- and two-dimensional NMR
spectra of samples in the indicated solvent were run at 300 MHz
(1H). Carbon multiplicities were determined by DEPT135 experi-
ments.18 Diagnostic correlation information was obtained using
the Bruker pulse program XHCORR12a for 1H-13C two- and
three-bond connectivities; delay times ∆1 and ∆219 of 35 ms (d3)
and 25 ms (d4) were used, respectively.12b Electron impact mass
spectra (EIMS) were obtained at 50-70 eV. Chemical ionization
low and high-resolution mass spectrometric analyses (CIMS,
HRMS) were obtained from the mass spectrometry laboratory
at the University of Texas at Austin. Combustion analyses were
performed by Desert Analytics (Tucson, AZ). 1H and13C NMR
spectra are provided to establish purity for those compounds
which were not subject to combustion analyses.
P r ep a r a tion of Or th oqu in ol Aceta tes 3a -e. A solution of
the phenol 2a -e (ca. 250 mg, 1.0 equiv) in dry CH2Cl2 (2 mL)
was added dropwise to a stirring solution of the oxidizing agent
[Pb(OAc)4, 1.1 equiv, or PhI(OAc)2, 1.0 equiv] in 5 mL of dry CH2-
Cl2 at -78 °C. The reaction mixture immediately became bright
yellow. After 1 h, TLC monitoring [hexanes-EtOAc (4:1)]
indicated complete consumption of the starting material. The
mixture was poured into ice-cold saturated aqueous NaHCO3
(20 mL), extracted with CH2Cl2 (2 × 20 mL), washed with brine
(20 mL), dried over Na2SO4 (vide infra), filtered and evaporated
at room temperature. The residue was further dried under high
vacuum overnight to give the corresponding orthoquinol acetate
3a -e as a bright yellow oil which was used without further
purification.
Or th oqu in ol a ceta te 3e. Yellow oil: Pb(OAc)4 w 99%, PhI-
1
(OAc)2 w 93%. IR (NaCl) 1737, 1684 cm-1; H NMR (CDCl3) δ
0.82 (d, J ) 6.4 Hz, 3H, Me-â), 0.86 (d, J ) 6.4 Hz, 3H, Me-â),
1.06 (s, 18H, 2 × tBu), 1.32-1.46 (m, 2H), 1.61-1.69 (m, 2H),
1.85-2.06 (m, 4H), 2.07 (s, 6H, 2 × AcO), 2.21-2.34 (m, 2H),
3.44 (s, 3H, MeO), 3.45 (s, 3H, MeO), 3.68-3.73 (m, 4H, 2 ×
CH2-δ), 5.89 (bs, 2H, 2 × H-2), 6.09 (d, J ) 10.0 Hz, 2 × H-5),
6.72 (dd, J ) 1.8, 10.0 Hz, 2H, 2 × H-6), 7.33-7.72 (m, 20H, 4
× Ph); 13C NMR (CDCl3) δ 191.9, 169.3, 142.9, 142.7, 137.5,
135.8, 135.5, 134.8, 133.8, 130.2, 129.7, 127.7, 127.6, 125.7, 125.6,
93.1, 61.7, 51.2, 42.6, 42.5, 39.2, 39.0, 28.4, 28.2, 26.8, 26.5, 20.5,
19.2, 19.1, 18.9; CIMS m/z (relative intensity) 507 (MH+, 9), 449
(47), 447 (23), 429 (23), 357 (100); HRMS (CI) calcd for C30H39O5-
Si 507.2566, found 507.2553.
Heter ocycliza tion of Or th oqu in ol Aceta tes 3a -e. To a
stirring ice-cold solution of commercial TBAF (1 M in THF, 2.0
equiv) in dry THF (ca. 30 mM) was added dropwise a solution
of the orthoquinol acetate (3a -e, 1.0 equiv) in dry THF (ca. 12
mM). After 10 min, the ice bath was removed, and the reaction
mixture was stirred at room temperature for 1-3 h. Progression
of the reaction was monitored by the disappearance of the
orthoquinol acetate, as indicated by TLC [hexanes-EtOAc, (4:
1)]. The mixture was quenched by adding dropwise a 1:1 mixture
of ice-cold water and 1 M H3PO4, and then diluted with EtOAc.
The organic layer was washed with brine, dried over Na2SO4,
filtered and evaporated to give a dark oil, which was subjected
to column chromatography, eluting with hexanes-EtOAc (9:1),
to give the cyclized product.
Or th oqu in ol a ceta te 3a . Yellow oil: Pb(OAc)4 w 96%, PhI-
1
(OAc)2 w 94%. IR (NaCl) 1738, 1694 cm-1; H NMR (CDCl3) δ
1.04 (s, 18H, 2 × tBu), 2.05 (s, 6H, 2 × AcO), 2.29-2.32 (m, 4H,
2 × CH2), 3.39 (s, 3H, MeO), 3.40 (s, 3H, MeO), 3.94-3.96 (m,
2H, 2 × CH), 5.82 (bs, 1H, H-2), 5.86 (bs, 1H, H-2), 5.95 (d, J )
10.0 Hz, 1H, H-5), 5.97 (d, J ) 10.0 Hz, 1H, H-5), 6.39 (dd, J )
2.0, 10.0 Hz, 1H, H-6), 6.52 (dd, J ) 2.0, 10.0 Hz, 1H, H-6), 7.33-
7.70 (m, 20H, 4 × Ph); 13C NMR (CDCl3) δ 191.7, 169.3, 143.5,
142.8, 135.8, 134.1, 133.9, 131.5, 131.4, 129.7, 129.6, 127.7, 127.6,
125.4, 125.1, 92.9, 68.9, 68.2, 51.2, 45.0, 44.8, 26.9, 22.4, 22.3,
20.5, 19.1; CIMS m/z (relative intensity) 478 (MH+, 6), 421 (23),
419 (33), 401 (23), 198 (100); HRMS (CI) calcd for C28H33O5Si
477.2097, found 477.2079.
1
Ben zofu r a n 5a . Brown oil (57%): IR (NaCl) 3432 cm-1; H
NMR (CDCl3) δ 1.42 (d, J ) 6.2 Hz, 3H, Me), 2.72 (ddd, J ) 0.6,
7.7, 14.8 Hz, 1H, CH2), 3.20 (dd, J ) 8.7, 14.8 Hz, 1H, CH2),
3.80 (s, 3H, MeO), 4.80-4.92 (m, 1H, CH), 5.59 (bs, 1H, OH),
6.39 (s, 1H, Harom.), 6.68 (s, 1H, Harom.); 13C NMR (CDCl3) δ 153.9,
140.7, 135.9, 116.6, 108.5, 97.2, 79.9, 57.0, 37.7, 21.6; CIMS m/z
(relative intensity) 181 (MH+, 100), 180 (25), 166 (11); HRMS
(CI) calcd for C10H12O3 180.0786, found 180.0784.
1
Ben zofu r a n 5b. Brown oil (73%): IR (NaCl) 3440 cm-1; H
NMR (CDCl3) δ 1.42 (s, 6H, 2 × Me), 2.90 (s, 2H, CH2), 3.79 (s,
Or th oqu in ol a ceta te 3b. Yellow oil: Pb(OAc)4 w 98%, PhI-
3H, MeO), 5.61 (s, 1H, OH), 6.37 (s, 1H, Harom.), 6.67 (s, 1H,
1
(OAc)2 w 98%. IR (NaCl) 1737, 1684 cm-1; H NMR (CDCl3) δ
H
arom.); 13C NMR (CDCl3) δ 153.3, 145.8, 140.5, 116.6, 108.7, 97.3,
86.9, 57.1, 43.0, 28.1; EIMS m/z (relative intensity) 194 (M+, 96),
179 (100). Anal. Calcd for C11H14O3: C, 68.01; H, 7.27. Found:
C, 67.85; H, 7.20.
0.54 (q, J ) 7.9 Hz, 6H, 3 × CH2-TES), 0.90 (t, J ) 7.9 Hz, 9H,
3 × CH3-TES), 1.20 (s, 3H, Me), 1.22 (s, 3H, Me), 2.06 (s, 3H,
AcO), 2.30 (s, 2H, CH2), 3.42 (s, 3H, MeO), 5.89 (bs, 1H, H-2),
5.99 (d, J ) 10.0 Hz, 1H, H-5), 6.97 (dd, J ) 2.1, 10.0 Hz, 1H,
H-6); 13C NMR (CDCl3) δ 191.9, 169.2, 144.9, 136.3, 132.2, 124.1,
93.0, 73.8, 51.2, 50.0, 29.8, 29.7, 20.5, 6.9, 6.6; EIMS m/z (relative
intensity) 369 (MH+, 41), 368 (M+, 37), 367 (80), 309 (20). Anal.
Calcd for C19H32O5Si: C, 61.92; H, 8.76. Found: C, 61.91; H,
9.04.
1
Ben zop yr a n 5c. Yellow oil (89%): IR (NaCl) 3436 cm-1; H
NMR (CDCl3) δ 1.91-1.99 (m, CH2-â), 2.68 (t, J ) 6.5 Hz, CH2-
R), 3.79 (s, MeO-3), 4.09 (t, J ) 5.1 Hz, CH2-γ), 5.55 (bs, OH),
6.40 (s, H-5), 6.49 (s, H-2); 13C NMR (CDCl3) δ 149.1 (C-6), 144.7
(C-4), 140.7 (C-3), 112.5 (C-1), 111.8 (C-2), 103.2 (C-5), 66.2 (CH2-
γ), 56.5 (MeO-3), 24.5 (CH2-R), 22.6 (CH2-â); EIMS m/z (relative
intensity) 180 (M+, 28), 165 (58), 69 (100). Anal. Calcd for
C10H12O3: C, 66.64; H, 6.72. Found: C, 66.71; H, 7.00.
Or th oqu in ol a ceta te 3c. Yellow oil: Pb(OAc)4 w 97%, PhI-
1
(OAc)2 w 98%. IR (NaCl) 1739, 1689 cm-1; H NMR (CDCl3) δ
1.04 (s, 9H, tBu), 1.67-1.76 (m, 2H, CH2-â), 2.06 (s, 3H, AcO),
2.35 (bt, J ) 7.6 Hz, 2H, CH2-R), 3.41 (s, 3H, MeO), 3.68 (t, J )
6.0 Hz, 2H, CH2-γ), 5.91 (bs, 1H, H-2), 6.09 (d, J ) 10.0 Hz, 1H,
Ben zop yr a n 5d . White crystals (36%): mp 115-116 °C; IR
1
(KBr) 3424 cm-1; H NMR (CDCl3) δ 1.15 (s, Me-γ), 1.19-1.64
(m, 8H), 1.87-1.91 (m, 1H), 2.22 (dd, J ) 1.0, -16.3 Hz, 1H,
CH2-R), 3.01 (dd, J ) 6.3, -16.3 Hz, 1H, CH2-R), 3.79 (s, MeO-
3), 5.44 (bs, OH), 6.39 (s, H-5), 6.48 (s, H-2); 13C NMR (CDCl3)
δ 147.3 (C-6), 144.8 (C-4), 140.5 (C-3), 111.9 (C-2), 110.1 (C-1),
103.6 (C-5), 74.5 (C-γ), 56.5 (MeO-3), 38.5 (CH2), 37.0 (CH-â),
(18) Doddrell, D. M.; Pegg, D. T.; Bendall, M. R. J . Magn. Reson.
1982, 48, 323-327.
(19) Bax, A.; Morris, G. A. J . Magn. Reson. 1981, 42, 501-505.

9600 J . Org. Chem., Vol. 63, No. 25, 1998
Notes
29.1 (CH2-R), 28.4 (CH2), 25.6 (CH2), 25.3 (Me-γ), 21.7 (CH2);
CIMS m/z (relative intensity) 249 (MH+, 100), 248 (M+, 36), 154
(35), 153 (39); HRMS (CI) calcd for C15H20O3 248.1412, found
248.1415.
Ack n ow led gm en t. We thank The Robert A. Welch
Foundation (Grant D-1365) for support of this research.
We also thank Mr. Roy T. Hendley for his contribution
to this work and Mr. David W. Purkiss for the NMR
spectroscopic analyses.
Ben zoxep in 5e. White crystals (20%): mp 67-68 °C; IR
(KBr) 3413 cm-1; 1H NMR (CDCl3) δ 0.99 (d, J ) 6.3 Hz, Me-â),
1.59-1.89 (m, 3H), 2.46-2.70 (m, 2H), 3.62 (ddd, J ) 2.1, 7.9,
-12.3 Hz, 1H, CH2-δ), 3.82 (s, MeO-3), 4.21 (ddd, J ) 2.9, 7.6,
-12.3 Hz, 1H, CH2-δ), 5.46 (bs, OH), 6.57 (s, H-5), 6.58 (s, H-2);
13C NMR (CDCl3) δ 154.5 (C-6), 144.0 (C-4), 142.2 (C-3), 124.9
(C-1), 112.8 (C-2), 108.0 (C-5), 72.2 (CH2-δ), 56.3 (MeO-3), 42.0
(CH2), 40.7 (CH2), 31.9 (CH-â), 22.4 (Me-â); EIMS m/z (relative
intensity) 208 (M+, 100), 193 (51), 153 (52); HRMS (CI) calcd
for C12H16O3 208.1099, found 208.1107.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectral characterizations for 2a -e and their
intermediates (16 pages). This material is contained in librar-
ies on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O9817669