Directed, DDQ-Promoted Benzylic Oxygenations of Tetrahydronaphthalenes

Article abstract of DOI:10.1021/jo981950u

Positional preferences for para benzylic oxygenation of tetrahydronaphthalenes by 2,3-dichloro5,6-dicyano-1,4-benzoquinone (DDQ)-aqueous dioxane were investigated by comparing the tetralone products from 6-hydroxy-7-methoxy- and 6-acetoxy-7-methoxy-1,2,3,

Full text of DOI:10.1021/jo981950u

J . Org. Chem. 1999, 64, 4607-4609
4607
Dir ected , DDQ-P r om oted Ben zylic Oxygen a tion s of
Tetr a h yd r on a p h th a len es
Frank D. Ramdayal, David J . Kiemle, and Robert T. LaLonde*
Department of Chemistry, J ahn Laboratory, State University of New York,
College of Environmental Science and Forestry, Syracuse, New York 13210
Received September 28, 1998 (Revised Manuscript Received February 18, 1999)
Positional preferences for para benzylic oxygenation of tetrahydronaphthalenes by 2,3-dichloro-
5,6-dicyano-1,4-benzoquinone (DDQ)-aqueous dioxane were investigated by comparing the tetralone
products from 6-hydroxy-7-methoxy- and 6-acetoxy-7-methoxy-1,2,3,4-tetrahydronaphthalene. The
directing influence by an aromatic substituent on para benzylic oxygenation was in the order OH
> OMe > OAc. Consistent with this finding were results obtained from lignan analogues. Treatment
of (+)-â-conidendryl alcohol with DDQ in dry dioxane resulted in the intramolecular bridging by
one of two primary hydroxy groups to the benzylic position, giving an oxabicyclo[3.2.1]octane. Similar
treatment of (+)-dimethyl-â-conidendryl alcohol resulted in bridging by the alternate primary
hydroxyl group to the benzhydrylic carbon giving an isomeric oxabicyclo[3.2.1]octane.
We have been interested in developing methods for
introducing oxygen selectively and efficiently at the
benzylic positions of 1,2,3,4-tetrahydronaphthalenes
(THN), including a number of lignans incorporating this
particular structural feature. Direct benzylic oxygen-
ations of simple 6-hydroxy- and 6-methoxytetrahydro-
naphthalenes have been achieved using 2,3-dichloro-
5,6-dicyano-1,4-benzoquinone (DDQ) in the presence of
water or methanol.1 We observe that treatment of
the dissymmetrically substituted THN, 1,2 with DDQ-
water results in a 70% yield of known tetralone 2.3 This
conversion demonstrated the preference for oxygena-
tion occurring at the methylene carbon para to the
hydroxy group, rather than para to the methoxy group,
and marks the terminal carbon involved in inter-
mediate quinone methide formation.4-6 However, the
preferred position for oxygenation can be switched to
the methylene para to the methoxy group. This change
was achieved by acetylating the hydroxy group of 1,
prior to DDQ-water treatment, for the purpose of
deactivating the hydroxy group.7 Thus, 3 yielded acetoxy-
tetralone 4 in 62% yield. Competitive formation of
2-acetoxy-3-methoxynaphthalene (23%) was anticipated
on the basis of known dehydrogenations by other chlorine-
substituted 1,4-benzoquinones.8 Acetoxytetralone 4 was
hydrolyzed, and the resulting hydroxytetralone 53 exhib-
ited physical properties agreeing with the assigned
structure and contrasting with those of its positional
isomer 2.
In contrast to the simple THN 1, its lignan analogue
(-)-â-conidendrin9 (Figure 1) gave the naphthalene de-
hydroconidendrin in 44% yield as the only isolable
product from DDQ-water treatment. Similarly, dim-
ethyl-â-conidendrin10 gave dimethyldehydroconidendrin
in 53% yield.10 However, dehydrogenation as the prin-
cipal outcome was replaced by an intramolecular
mode of oxygenation through treatment of (+)-â-coni-
dendryl alcohol (6, Scheme 1) in anhydrous dioxane
with DDQ. Oxymethylene bridging to the benzylic
carbon of 6 occurred giving 7 (59%). The structure was
consistent with the physical data including the HMBC.
Oxymethylene bridging switched from the benzyl to
the benzhydrylic position when the phenolic hydroxy
groups of 6 were replaced by methoxy groups, as dem-
onstrated by the conversion of 810 to 9 (70%) using
DDQ in CH2Cl2. Persistence of some competitive dehy-
drogenation was evident in the formation of the
naphthalene 10 (2%). Compound 9 was an inseparable
* To whom correspondence should be addressed. Phone: (315) 470-
6823. Fax: (315) 470-6856. E-mail: rtlalond@syr.edu.
(1) Findlay, J . W. A.; Turner, A. B. J . Chem. Soc. C 1971, 23.
(2) Boger, D. L.; Coleman, R. S. J . Org. Chem. 1986, 51, 5436.
(3) Grethe, G.; Toome, V.; Lee, H. L.; Uskokovic, M.; Brossi, A. J .
Org. Chem. 1968, 33, 504.
(4) Becker, H.-D. J . Org. Chem. 1965, 30, 982.
(5) Becker, H.-D. J . Org. Chem. 1965, 30, 989.
(6) Becker, H.-D. J . Org. Chem. 1969, 34, 1203.
(7) Bouquet, M.; Guy, A.; Lemaire, M.; Guette, J . P. Synth. Commun.
1985, 15, 1153.
(9) Hearon, W. M.; Lackey, H. B.; Moyer, W. W. J . Am. Chem. Soc.
1951, 73, 4005.
(8) Kosak, A. I.; Palchak, J . F.; Steele, W. A.; Selwitz, C. M. J . Am.
Chem. Soc. 1954, 76, 4450.
(10) Cisney, M. E.; Shilling, W. L.; Hearon, W. M.; Goheen, D. W.
J . Am. Chem. Soc. 1954, 76, 5083.
10.1021/jo981950u CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/06/1999

4608 J . Org. Chem., Vol. 64, No. 13, 1999
Ramdayal et al.
dropwise to the THN in ∼5% aqueous dioxane. Processing the
reaction mixture involved the following steps in succession:
filtration if required through sintered glass, evaporation of the
solvent from the filtrate, and partitioning of the residue
between EtOAc and 5% aqueous NaHCO3. The EtOAc layer
was washed with proportional amounts of 5% aqueous NaH-
CO3, H2O, and brine. The residue obtained on removal of the
EtOAc at reduced pressure was chromatographed. (b) Rea c-
tion of (+)-â-Con id en d r yl Alcoh ol, 6. The reaction proce-
dure and processing were the same as described in part a,
except 6 was dissolved in anhydrous dioxane. (c) Rea ction
of (+)-Dim eth yl-â-con id en d r yl Alcoh ol, 8. DDQ in CH2-
Cl2 was added dropwise to 8 in CH2Cl2. Processing solvent
Et2O replaced EtOAc.
F igu r e 1. Tetrahydronaphthalene lignans â-conidendrin (R
) H) and dimethyl-â-conidendrin (R ) CH3) undergoing
dehydrogenation with DDQ in dioxane-5% water to dehydro-
conidendrin and dimethyldehydroconidendrin, respectively.
Con ver sion of 6-Hyd r oxy-7-m eth oxy-1,2,3,4-tetr a h y-
d r on a p h th a len e (1)2 to Tetr a lon e 2. DDQ (231 mg, 1.02
mmol) in 2 mL of dry dioxane and 1 (89 mg, 0.5 mmol) in 0.5
mL of aqueous dioxane gave after 3 h and MPLC (EtOAc/
hexane 1:1) compound 2 (68 mg, 71%): mp 117-119 °C (lit.3
mp 115-118 °C); IR (film, NaCl disk, cm-1) 3338, 1664; 1H
NMR (300 MHz, CDCl3) δ 2.07 (m, 2), 2.57 (t, J ) 6.53 Hz, 2),
2.83 (t, J ) 6.11 Hz, 2), 3.88 (s, 3), 6.44 (s, 1, OH), 6.73 (s, 1),
7.51 (s, 1); 13C NMR (75 MHz, CDCl3) δ 23.5, 29.2, 38.5, 56.1,
108.5, 113.8, 125.6, 140.1, 145.7, 150.8, 197.3; MS 192 [M+].
Con ver sion of 6-Acet oxy-7-m et h oxy-1,2,3,4-t et r a h y-
d r on a p h th a len e (3) to Tetr a lon e 4 a n d 2-Acetoxy-3-
m eth oxyn a p h th a len e. DDQ (454 mg, 2 mmol) in 4 mL of
dry dioxane and 3 (220 mg, 1 mmol) in 1 mL of aqueous
dioxane gave after 20 h and MPLC (EtOAc/hexanes 3:5) 4 (146
mg, 62%) and 2-acetoxy-3-methoxynaphthalene (50 mg, 23%).
4: mp 118.5-119.5 °C; IR (film, NaCl disk, cm-1) 1675, 1769;
1H NMR (300 MHz, CDCl3) δ 2.11 (m, 2), 2.28 (s, 3), 2.57 (t, J
) 6.53 Hz, 2), 2.91 (t, J ) 6.08 Hz, 2), 3.86 (s, 3), 6.74 (s, 1),
7.69 (s, 1); 13C NMR (75 MHz, CDCl3) δ 20.4, 23.2, 29.7, 38.4,
56.0, 111.3, 121.5, 126.1, 138.7, 144.5, 155.2, 168.8, 196.2; MS
234 [M+]. 2-Acetoxy-3-methoxynaphthalene: mp 114-116 °C;
IR 1764; 1H NMR δ 2.38 (s, 3), 3.95 (s, 3), 7.22 (s, 1), 7.36 (ddd,
J ) 8.14, 7.51, 1.24 Hz, 1), 7.44 (ddd, J ) 8.23, 7.55, 1.34 Hz,
1), 7.50 (s, 1), 7.73 (dd, J ) 7.43, 1.1 Hz, 1), 7.75 (dd, J ) 8.13,
1.0 Hz, 1); 13C NMR (75 MHz, CDCl3) δ 20.6, 55.8, 107.3, 120.3,
124.2, 126.1, 126.5, 127.2, 128.3, 132.5, 140.3, 150.2, 169.2;
HRMS calcd for C13H12O3 216.0786 [M+], found 216.0783.
Con ver sion of 6-Meth oxy-7-a cetoxy-1-tetr a lon e (4) to
Tetr a lon e 5. To 4 (117 mg, 0.5 mmol) in 7 mL of methanol
was added 3.5 mL of water and then 3.5 mL of saturated
aqueous NaHCO3. The resulting solution was stirred under
N2 at 25 °C for 17 h, acidified with aqueous HCl (1 M), and
extracted with CH2Cl2 (5 × 6 mL). The combined CH2Cl2
mixture of near-equimolar amounts of rotational diaster-
eomers, as evidenced by pairs of signals in the 13C
NMR.
The demonstrated influence of a C-6 aromatic sub-
stituent on para benzylic oxygenation of a THN is in the
order OH > OCH3 > OAc. This finding allows for
selectivity in DDQ-promoted oxygenations of benzylic
positions through appropriate, prior blocking of a para
phenolic hydroxy group. This was demonstrated by the
simple disubstituted THNs and the more complex (+)-
â-conidendryl and dimethyl-â-conidendryl alcohols.
Exp er im en ta l Section
Rea ction P r oced u r es. All reactions with DDQ were
conducted under N2 at 25 °C. (a ) Rea ction s of THNs 1 a n d
3. DDQ in anhydrous dioxane (<0.01% H2O) was added
Sch em e 1

Benzylic Oxygenations of Tetrahydronaphthalenes
J . Org. Chem., Vol. 64, No. 13, 1999 4609
extracts were washed with brine and dried (MgSO4). Removal
of CH2Cl2 at reduced pressure gave 5 (94 mg, 98%): mp 151-
152 °C (lit.3 mp 148-152 °C); IR (film, NaCl disk, cm-1) 3369,
3), 4.22 (m, 2), 6.12 (s, 1), 6.16 (s, 1), 6.56 (d, J ) 1.76 Hz, 1),
6.66 (dd, J ) 1.95, 8.36 Hz, 1), 6.65 (s, 1), 6.67 (s, 1), 6.86 (d,
J ) 8.39 Hz, 1), 6.90 (d, J ) 8.31 Hz, 1), 7.32 (dd, J ) 8.31,
1.81 Hz, 1), 7.36 (d, J ) 1.59 Hz, 1); 13C NMR (75 MHz, CDCl3)
δ 37.73, 37.74, 38.15, 38.19, 52.94, 53.14, 55.73, 55.79, 55.92,
55.94, 56.06, 62.56, 62.58, 71.43, 71.48, 86.05, 86.14, 110.33,
110.41, 110.47, 110.63, 111.00, 111.97, 112.03, 119.29, 119.77,
126.94, 127.17, 131.62, 132.23, 135.09, 135.36, 146.90, 146.97,
147.70, 148.38, 148.54, 148.69; HRMS calcd for C22H26O6
386.1729, found 386.1732. Also obtained by MPLC was 10 (63
1
1665; H NMR (300 MHz, CDCl3) δ 2.09 (m, 2H), 2.57 (t, J )
6.54 Hz, 2), 2.86 (t, J ) 6.11 Hz, 2), 3.93 (s, 3), 5.68 (s, 1), 6.65
(s, 1), 7.55 (s, 1); 13C NMR (75 MHz, CDCl3) δ 23.6, 29.5, 38.6,
56.0, 109.7, 112.3, 126.6, 138.4, 144.5, 151.2, 197.2; MS 192
[M+].
Con ver sion of (+)-â-Con id en d r yl Alcoh ol (6) to Ox-
a bicycloocta n e 7. DDQ (150 mg, 0.66 mmol) in 8.5 mL of
dioxane and 6 (200 mg, 0.56 mmol) in 45 mL of dioxane gave
7 (117 mg, 59%) after a 5 h reaction period, processing, and
preparative TLC (EtOAc). 7: mp 167-169 °C; [R]25D ) -30.95°
(c 1.58, acetone); IR 3370 (film, NaCl disk, cm-1); 1H NMR (300
MHz, MeOH-d4) δ 2.54 (m, 2), 3.38 (dd, J ) 10.92, 6.20 Hz, 1),
3.59 (dd, J ) 10.73, 9.17 Hz, 1), 3.75 (d, J ) 8.57 Hz, 1), 3.83
(s, 3), 3.94 (s, 3), 4.10 (dd, J ) 8.58, 5.94 Hz, 1), 4.18 (d, J )
1.65 Hz, 1), 4.84 (brs, 4), 6.50 (dd, J ) 8.14, 1.88 Hz, 1), 6.54
(s, 1), 6.72 (d, J ) 1.87 Hz, 1), 6.78 (d, J ) 8.12 Hz, 1), 6.88 (s,
1); 13C (75 MHz, CDCl3) δ 45.5, 46.6, 53.7, 56.4, 56.5, 62.8,
71.8, 79.4, 112.8, 113.8, 115.9, 118.7, 122.5, 130.3, 133.2, 138.2,
146.1, 147.7, 147.8, 148.8; HRMS calcd for C20H22O6 358.1416,
found 358.1417.
1
mg, 2%): mp 193-194 °C; H NMR (300 MHz, CDCl3) δ 3.71
(s, 3), 3.85 (s, 3), 3.98 (s, 3), 3.99 (s, 3), 4.60 (d, J ) 11.93 Hz,
1), 4.64 (d, J ) 11.96 Hz, 1), 4.91 (s, 2), 6.77 (s, 1), 6.89 (m, 2),
7.00 (dd, J ) 6.78, 1.90 Hz, 1), 7.13 (s, 1), 7.70 (s, 1); 13C NMR
(75 MHz) δ 55.65, 55.89, 55.92, 55.97, 60.82, 65.4, 106.1, 106.3,
111.2, 113.6, 122.5, 127.2, 128.6, 128.8, 131.4, 133.2, 135.7,
139.2, 148.3, 148.8, 149.7, 149.8; HRMS calcd for C22H24O6
384.1573, found 384.15601.
Ack n ow led gm en t. This work was supported by the
McIntire-Stennis, USDA-CREES program, and SUNY-
ESF. Determination of high-resolution mass spectra by
the Midwest Center for Mass Spectrometry, University
of Nebraska-Lincoln, is also acknowledged.
Con ver sion of (+)-Dim eth y-â-con id en d r yl Alcoh ol (8)10
to Oxa bicycloocta n e 9 a n d Na p h th a len e 10. DDQ (2.32
g, 10.22 mmol) in 118 mL of CH2Cl2 and 8 (3.5 g, 9.18 mmol)
in 60 mL of CH2Cl2 gave 9 (2.48 g, 70%) after a 5.5 h reaction
period, processing, and MPLC (CH2Cl2/EtOAc 1:1). 9: mp 121-
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, compound characterization, and selected interpreta-
tions of HMBC are provided for 3, dehydroconidendrin,
dimethyldehydroconidendrin, 6, 7, and 9. This material is
available free of charge via the Internet at http://pubs.acs.org.
122 °C; [R]22 ) -6.7° (c 1.93, acetone); IR 3450 (film, NaCl
D
disk, cm-1); 1H NMR (300 MHz, CDCl3) δ 1.43 (br s, 2H), 2.55
(t, J ) 6.28 Hz, 2), 2.89 (m, 4), 3.22 (m, 1), 3.29 (m, 3), 3.43
(m, 2), 3.51 (s, 3), 3.52 (s, 3), 3.741 (s, 3), 3.745 (d, J ) 8.51
Hz, 2), 3.826 (s, 3), 3.833 (s, 3), 3.89 (s, 3), 3.90 (s, 3), 3.92 (s,
J O981950U