Bis(o-nitrophenyl)ethanediol: A practical photolabile protecting group for ketones and aldehydes

Article abstract of DOI:10.1021/jo026347x

The ketals of bis(o-nitrophenyl)ethanediol and ketones or aldehydes are smoothly deprotected in neutral conditions by irradiation with 350 nm light. The chemical stability in basic, acidic, and oxidizing media makes this form of protection orthogonal to classical protecting groups. Both racemic and enantiopure forms are readily available in two steps from inexpensive starting materials.

Full text of DOI:10.1021/jo026347x

SCHEME 1
Bis(o-n itr op h en yl)eth a n ed iol: A P r a ctica l
P h otola bile P r otectin g Gr ou p for Keton es
a n d Ald eh yd es
Aure´lien Blanc and Christian G. Bochet*,1
Department of Organic Chemistry, University of Geneva, 30,
quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland
christian.bochet@unifr.ch
Received August 23, 2002
the other half as a free OH group. This strategy has been
utilized with the o-nitrophenylethylene glycol as a pro-
tecting group for ketones and aldehydes.4 However,
several drawbacks limit its general use in organic
synthesis. The presence of a chiral center leads to the
formation of two diastereoisomers when used with an-
other chiral molecule,4 making already complicated NMR
signal patterns (two sets of signals) more difficult to
interpret. Purification of the resulting pair of compounds
can also be cumbersome. These issues were addressed
by using two units of o-nitrobenzyl alcohol instead of a
diol.6 Nevertheless, an excess of diol in the ketalization
and significant lability in acidic media are other draw-
backs that render their application useful in only very
specific cases.
Abstr a ct: The ketals of bis(o-nitrophenyl)ethanediol and
ketones or aldehydes are smoothly deprotected in neutral
conditions by irradiation with 350 nm light. The chemical
stability in basic, acidic, and oxidizing media makes this
form of protection orthogonal to classical protecting groups.
Both racemic and enantiopure forms are readily available
in two steps from inexpensive starting materials.
Photochemical lability is an attractive feature for a
protecting group, since it allows deprotection without the
requirement of any reagent. This permits the handling
of compounds very sensitive to acids, bases, or other
chemical conditions. Many photolabile protecting groups
are known, mainly for the protection of carboxylic acids
(as esters or amides), amines (as carbamates), and
alcohols (as carbonates).2 On the other hand, there are
very few of such groups for ketones and aldehydes.3,4 This
is quite surprising, since carbonyl compounds are among
the most commonly protected functions in organic syn-
thesis. In this work, we describe a new photosensitive
group, highly labile under photochemical conditions, but
otherwise very robust in many chemical conditions.
Upon excitation by UV-light (λ < 400 nm), o-nitroben-
zylic derivatives are capable of intramolecular hydrogen
abstraction, followed by oxygen transfer from the nitro
group.5 The formal result is the oxidation of the benzylic
center. If this position is functionalized with an alkoxy
group, a hemiketal is formed, which spontaneously
decomposes into the corresponding ketone, and liberates
As an alternative, we have prepared the more robust
diol 3, symmetrical and easily accessible in its enan-
tiopure form (Scheme 1). It was prepared by simple
treatment of inexpensive o-nitrobenzyl chloride 1 with
potassium hydroxide,7 followed by osmium-catalyzed
dihydroxylation (1 mol % OsO4, NMO, water/CH2Cl2,
83%) of the trans-stilbene 2. The asymmetric version was
also carried out by using a slightly modified Sharpless
dihydroxylation (1 mol % of DHQD2PHAL, 1 mol % of
OsO4, 1.25 equiv of NMO, 1 equiv of MeSO2NH2, water/
CH2Cl2).8 The crude enantiomeric excess (93% ee, mea-
sured by chiral SFC) was increased by a recrystallization
(82%, 99% ee). The absolute configuration of (-)-3 was
tentatively assigned to (R,R), by analogy to stilbene.8b
t
Standard conditions with AD-mix-R in BuOH/water gave
poor or no conversion, presumably due to the poor
solubility of the substrate.
(1) Present address: Department of Chemistry, University of Fri-
bourg, Chemin du Muse´e 9, CH-1700 Fribourg, Switzerland. E-mail:
Christian.Bochet@unifr.ch. Fax: +41-26-300 9738.
(2) For reviews on photolabile protecting groups, see: (a) Pillai, V.
N. R. Synthesis 1980, 1-26. (b) Pillai, V. N. R. Org. Photochem. 1987,
9, 225-321. (c) Bochet, C. G. J . Chem. Soc., Perkin 1 2002, 125-142.
(3) McHale, W. A.; Kutateladze, A. G. J . Org. Chem. 1998, 63, 9924-
9931.
(4) (a) Gravel, D.; Hebert, J . Can. J . Chem. 1974, 52, 187-189. (b)
Sam, D. J . U.S. Patent 4,111,960, 1978. (c) Gravel, D.; Hebert, J .;
Thoraval, D. Can. J . Chem. 1983, 61, 400-410. (d) Aurell, M. J .; Boix,
C.; Ceita, M. L.; Llopis, C.; Tortajada, A.; Mestres, R. J . Chem. Res.
(S) 1995, 452-453. (e) Ceita, L.; Mestres, R.; Tortajada, A. Bol. Soc.
Quim. Peru´ 1998, 64, 55-61. (f) Ceita, L.; Maiti, A. K.; Mestres, R.;
Tortajada, A. J . Chem. Res. (S) 2001, 403-404.
(5) (a) Ciamician, G.; Silber, P. Chem. Ber. 1901, 34, 2040-2046.
(b) Patchornik, A.; Amit, B.; Woodward, R. B. J . Am. Chem. Soc. 1970,
92, 6333-6335. For more recent mechanistic work, see: (c) Yip, R.
W.; Sharma, D. K.; Giasson, R.; Gravel, D. J . Phys. Chem. 1985, 89,
5328-5330. (d) Walker, J . W.; Reid, G. P.; McCray, J . A.; Trentham,
D. R. J . Am. Chem. Soc. 1988, 110, 7170-7177. (e) Yip, R. W.; Wen,
Y. X.; Gravel, D.; Giasson, R.; Sharma, D. K. J . Phys. Chem. 1991, 95,
6078-6081. (f) Il’Ichev, Y. V.; Wirz, J . J . Phys. Chem. (A) 2000, 104,
7856-7870. For additional references, see ref 2.
To test this new photosensitive group, the protection
of various types of ketones and aldehydes was carried
out in refluxing benzene with a Dean-Stark apparatus
(10 mol % PPTS). Deprotection was performed by expos-
ing the ketals to UV-light (350 nm) for 1-2 h. Yields were
high, in both protection and deprotection (Scheme 2,
Table 1). It is worth mentioning the absence of double
(6) Gravel, D.; Murray, S.; Ladouceur, G. J . Chem. Soc., Chem.
Commun. 1985, 1828-1829.
(7) (a) Bischoff, C. A. Ber. Deutsch. Chem. Ges. 1888, 21, 2071-
2078. (b) Ehrensperger, C. P.; Heberlein, M.; Skrabal, P. Helv. Chim.
Acta 1978, 61, 2813-2822.
(8) (a) Kolb, H. C.; Van Nieuwenzhe, M. S.; Sharpless, K. B. Chem.
Rev. 1994, 94, 2483-2547. (b) Sharpless, K. B.; Amberg, W.; Bennani,
Y. L.; Crispino, G. A.; Hartung, J .; J eong, K. S.; Kwong, H. L.;
Morikawa, K.; Wang, Z. M.; Xu, D.; Zhang, X. L. J . Org. Chem. 1992,
57, 2768-2771. (c) Wang, Z. M.; Sharpless, K. B. J . Org. Chem. 1994,
59, 8302-8303.
10.1021/jo026347x CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/24/2002
1138
J . Org. Chem. 2003, 68, 1138-1141

TABLE 3
SCHEME 2
solvent
reagent
conditions
5b
4b
THF
THF
THF
THF
THF
THF
TFA
HCl 5%a
25 °C, 16 h
25 °C, 16 h
25 °C, 16 h
25 °C, 16 h
25 °C, 16 h
25 °C, 72 h
25 °C, 1 h
100
100
100
96
98
99
0
0
0
HCl 10%a
AcOH 10%a
p-TsOH 3 mol %
oxalic acid 2 mol %
H2SO4 10%a
trace
trace
trace
30
68
a
TABLE 1
THF/aqueous solution (1:1 v/v).
TABLE 4
solvent
reagent
conditions
5b
4b
THF
TBAF, 1 equiv
CAN, 4 equiv
DDQ, 4 equiv
25 °C, 16 h
25 °C, 16 h
25 °C, 18 h
25 °C, 24 h
25 °C, 1 h
25 °C, 1 h
75
97
90
100
98
0
13
3
8
0
trace
0
MeCNa
MeCN
piperidine
MeOH
Et2O
NaBH4
LiAlH4
a
With 50% water.
sulfuric acid). On the other hand, neat trifluoroacetic acid
should be avoided.
Finally, conditions used to hydrolyze other protecting
groups showed that the compatibility is also satisfactory,
except for fluoride source and strongly reducing agents
(reactive against the nitro groups of 5b).
a
b
Yield determined by GC or NMR (isolated yield). Volatile
products.
In conclusion, we have developed a symmetrical, enan-
tiopure photolabile protecting group for ketones and
aldehydes. Its improved stability ensures real orthogo-
nality with respect to other existing groups. We are
currently examining the possibility of tuning its reactivity
according to the wavelength.9
TABLE 2
solvent
reagent
conditions
25 °C, 10 h
5b
4b
CH2Cl2
THF
DME
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaH, 5 equiv
NaOH 2N
100
92
100
80
59
97
100
100
99
0
91
0
25 °C, 10 h
25 °C, 10 h
25 °C, 10 h
25 °C, 10 h
25 °C, 10 h
25 °C, 10 h
25 °C, 10 h
reflux, 10 h
110 °C, 14 h
reflux, 24 h
25 °C, 24 h
reflux, 24 h
25 °C, 24 h
-78 to 25 °C, 10 h
trace
0
DMF
17
trace
trace
Exp er im en ta l Section
DMSO
PhMe
Et2O
MeCN
PhH
All reactions were carried out under argon, with magnetic
stirring, unless otherwise specified. Purchased chemicals were
used without further purification, unless otherwise specified.
Solvents were dried by distillation from drying agents as
follows: Et2O and THF (Na/benzophenone); toluene and benzene
(Na); MeCN and CH2Cl2 (CaH2); MeOH (Mg(OMe)2). Flash
column chromatography (FC): SiO2. Melting points were uncor-
rected.
0
0
0
0
9
0
DMSO
H2Oa
EtOHa
EtOHa
tBuOH
THF
EtONa
100
51
12
EtONa
29
6
tBuOK
tr a n s-2,2′-Din itr ostilben e (2). KOH (4.17 g, 74.5 mmol)
dissolved in 40 mL of EtOH was slowly added to a solution of
o-nitrobenzyl chloride 1 (4.26 g, 24.8 mmol) in 10 mL of EtOH.
The mixture was stirred at room temperature for 4 h (formation
of a yellow solid). The solid was filtered and washed several
times with EtOH. The KCl remaining was removed by dissolu-
tion in hot AcOEt and filtration. Recrystallization (AcOEt) gave
2 (1.6 g, 48%) as a yellow solid: mp 204 °C; TLC Rf 0.42
(cyclohexane/AcOEt 3/2); IR (CHCl3) νmax 3020, 1525, 1345, 1275
LDA
92
8
a
With 50% dioxane.
bond isomerization in unsaturated ketones or aldehydes
(entries 5-7). In the latter case, the use of 4 Å molecular
sieves was essential to avoid deconjugation during the
formation of the ketal.
Stability against a broad variety of chemical condi-
tions is critical to a protecting group. We tested the
stability of ketal 5b in basic conditions (Table 2), acidic
conditions (Table 3), and other commonly used reagents
(Table 4).
Strong bases did not decompose the ketal, unless in
the presence of nucleophilic solvents (DMSO, alcohols).
It is worth pointing out that the stability in basic media
is markedly higher than that with previously known
ketone photolabile groups.4,6
1
cm-1; H NMR (400 MHz, CDCl3) δ 7.48 (td, J ) 7.8, 1.3 Hz, 2
H), 7.57 (s, 2 H), 7.67 (td, J ) 7.7, 1.3 Hz, 2 H), 7.81 (dd, J )
7.8, 1.3 Hz, 2 H), 8.04 (dd, J ) 8.1, 1.3 Hz, 2 H); 13C NMR (100
MHz, CDCl3) 124.9, 128.9, 129.0, 129.1, 132.6, 133.6, 147.9; MS
(EI) m/z (%) 270 (2, M+•), 206 (4), 195 (7), 176 (21), 165 (46), 151
(56), 135 (75), 119 (52), 104 (58), 92 (100); HR-MS 270.0618
(C14H10O4N2 calcd 270.0606).
(1R*,2R*)-1,2-Bis(2-n itr oph en yl)eth an e-1,2-diol ((3). OsO4
(96 µL, 0.015 mmol, 4% in water) was added to a solution of
trans-stilbene 2 (405 mg, 1.5 mmol) and N-methylmorpholine
N-oxide (NMO, 400 µL, 1.9 mmol, 50% in water) in 10 mL of
CH2Cl2/H2O (4/1). The reaction was vigorously stirred at room
The stability in acidic media is also significantly better,
even in the presence of aqueous strong acids (such as
(9) Blanc, A.; Bochet, C. G. J . Org. Chem. 2002, 67, 5567-5577.
J . Org. Chem, Vol. 68, No. 3, 2003 1139

temperature for 48 h (follow the reaction by TLC). The reaction
was quenched with Na2S2O4 (1.2 g in 10 mL of water). After 24
additional hours of stirring, the aqueous phase was extracted
with AcOEt. The combined organic layers were washed with
brine, dried over MgSO4, filtered, and evaporated. The purifica-
tion by FC (cyclohexane/AcOEt 2/1) gave ((3) (380 mg, 83%) as
a white-gray solid: mp 142 °C; TLC Rf 0.29 (cyclohexane/AcOEt
3/2); IR (CHCl3) νmax 3500, 3020, 1530, 1350 cm-1; 1H NMR (400
MHz, CDCl3) δ 3.37 (d, J ) 4.5 Hz, 2 H), 5.60 (d, J ) 4.5 Hz, 2
H), 7.45 (td, J ) 8, 1.3 Hz, 2 H), 7.62 (td, J ) 7.8, 1.3 Hz, 2 H),
7.78 (dd, J ) 5, 1.3 Hz, 2 H), 7.80 (dd, J ) 5.2, 1.3 Hz, 2 H);
13C NMR (100 MHz, CDCl3) 71.9, 124.5, 129.0, 129.5, 133.2,
134.8, 148.6; MS (EI) m/z (%) 152 (13), 135 (56), 121 (68), 93
(48), 77 (75), 65 (72), 51 (100); HR-MS 152.0334 (C7H6O3N calcd
152.0347).
2 H), 7.83 (dd, J ) 7.8, 1.3 Hz, 1 H), 7.90 (m, 3 H); 13C NMR
(100 MHz, CDCl3) 14.1, 22.7, 23.9, 29.3, 29.6, 29.7, 31.9, 34.2,
80.3, 80.6, 106.2, 124.4, 124.7, 128.2, 128.7, 129.0, 129.1, 133.5,
133.7, 133.9, 134.6, 148.3, 148.4; MS (EI) m/z (%) 315 (41), 152
(17), 135 (100), 104 (15); HR-MS 315.0626 (C15H11O6N2 calcd
315.0617; C26H34O6N2-C11H23).
4,5-Bis(2-n it r op h en yl)-2-p h en et h yl[1,3]d ioxola n e (5d ).
Following the general procedure, the hydrocinnamaldehyde 4d
(67 mg, 0.5 mmol) and the diol ((3) (167 mg, 0.55 mmol) in the
presence of PPTS (12.5 mg, 0.05 mmol) gave 5d (160 mg, 85%)
as a yellow oil: TLC Rf 0.43 (cyclohexane/AcOEt 3/1); IR (CHCl3)
νmax 3030, 2930, 2865, 1530, 1350, 1135, 1035 cm-1 1H NMR
;
(400 MHz, CDCl3) δ 2.27 (m, 2 H), 2.93 (m, 2 H), 5.53 (t, J ) 4.7
Hz, 1 H), 5.65 (ab, J ab ) 6.5 Hz, 2 H), 7.23-7.36 (m, 5 H), 7.52
(m, 2 H), 7.73 (m, 2 H), 7.82 (dd, J ) 7.8, 1.3 Hz, 1 H), 7.93 (m,
3H); 13C NMR (100 MHz, CDCl3) 30.0, 35.7, 80.4, 80.6, 105.2,
124.4, 124.7, 126.0, 128.2, 128.4, 128.5, 128.6, 129.0, 129.1, 133.4,
133.5, 133.6, 134.4, 141.0, 148.3, 148.4; MS (EI) m/z (%) 315 (3),
165 (3), 152 (13), 135 (100), 119 (14); HR-MS 315.0620
(C15H11O6N2 calcd 315.0617; C23H20O6N2-PhCH2CH2).
(1R,2R)-1,2-Bis(2-n itr oph en yl)eth an e-1,2-diol ((-)-3). NMO
(50% in water, 530 µL, 2.5 mmol) was added to a solution of
trans-stilbene 2 (540 mg, 2 mmol), (DHQD)2PHAL (20 mg, 0.025
mmol), CH3SO2NH2 (190 mg, 2 mmol), and OsO4 (4% in water,
130 µL, 0.02 mmol). The mixture was stirred at 0 °C for 4 h.
The enantiomeric excess was determined, after FC (cyclohexane/
AcOEt 2/1), by SFC (Chiralcel ODH, 0.46 cm L × 25 cm, 15%
2,3-Bis(2-n itr op h en yl)-1,4-d ioxa -sp ir o[4.5]d ec-6-en e (5e).
Following the general procedure, the cyclohexenone 4e (24 mg,
0.25 mmol) and the diol ((3) (76 mg, 0.25 mmol) in the presence
of PPTS (7 mg, 0.025 mmol) gave 5e (79 mg, 83%) as a yellow
oil: TLC Rf 0.25 (cyclohexane/AcOEt 9/1); IR (CHCl3) νmax 2930,
MeOH in CO2, 200 bar CO2, 30 °C, T1 ) 4.3 min (1R,2R), T2
)
4.8 min (1S,2S); 93% ee). Recrystallization in toluene gave (-)-3
(142 mg, 82%, 99% ee) as white-gray crystals: mp 172 °C; [R]17
D
-30.1 (4.7 mg‚mL-1, CHCl3).
2855, 1530, 1350, 1220, 1205, 1115 cm-1 1H NMR (400 MHz,
;
Gen er a l P r oced u r e for th e Aceta liza tion . In a flask under
argon equipped with a Dean-Stark water separator, a solution
of distilled aldehyde or ketone (1 mmol), 1,2-diol 3 (1.0-1.2
mmol) and pyridinium p-toluenesulfonate (PPTS, 25 mg, 0.1
mmol) in 10 mL of dry benzene were stirred at reflux. After
completion of the reaction (monitored by TLC), the benzene was
distilled and AcOEt was added. The organic phase was washed
once with a satd NaHCO3 solution and once with brine, dried
over MgSO4, filtered, and evaporated. The residue was purified
by FC (silica gel, cyclohexane/AcOEt).
CDCl3) δ 1.90 (m, 2 H), 2.13 (m, 4 H), 5.53 (ab, J ab ) 8.1 Hz, 2
H), 5.91 (d, J ) 9.9 Hz, 1 H), 6.13 (dt, J ) 10.1 Hz, 1 H), 7.48
(td, J ) 8.1, 1.3 Hz, 2 H), 7.72 (td, J ) 7.8, 1.3 Hz, 2 H), 7.81
(dd, J ) 8.1, 1.3 Hz, 2 H), 7.97 (dd, J ) 8.1, 1.3 Hz, 2 H); 13C
NMR (100 MHz, CDCl3) 20.6, 24.8, 34.8, 79.4, 79.9, 106.9, 124.3,
127.5, 128.9, 129.1, 129.2, 132.1, 132.1, 133.4, 133.5, 134.1, 148.8;
MS (EI) m/z (%) 354 (3), 135 (100), 97 (11), 91 (34); HR-MS
354.0857 (C18H14O6N2 calcd 354.0852; C20H18O6N2-C2H4).
2-Hex-1-en yl-4,5-bis(2-n itr op h en yl)[1,3]d ioxola n e (5f).
Following the general procedure, the trans-heptenal 4f (28 mg,
0.25 mmol) and the diol ((3) (91 mg, 0.3 mmol) in the presence
of PPTS (7 mg, 0.025 mmol) gave 5f (88 mg, 88%) as a yellow
oil: TLC Rf 0.31 (cyclohexane/AcOEt 3/1); IR (CHCl3) νmax 2930,
2855, 1530, 1350, 1130, 1035 cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.92 (t, J ) 7.2 Hz, 3 H), 1.25-1.50 (m, 4 H), 2.16 (q, J ) 7.1
Hz, 2 H), 5.68 (ab, J ab ) 6.1 Hz, 2 H), 5.75-5.80 (m, 2 H), 6.12
(dt, J ) 6.6 Hz, 1 H), 7.51 (td, J ) 7.8, 1.0 Hz, 2 H), 7.71 (qd, J
) 8.3, 1.0 Hz, 2 H), 7.74-7.94 (m, 4 H); 13C NMR (100 MHz,
CDCl3) 13.9, 22.2, 30.6, 31.8, 80.1, 80.6, 105.8, 124.5, 124.8,
125.3, 128.2, 128.8, 129.1, 133.5, 133.7, 133.9, 134.2, 139.8, 148.3,
148.5; MS (EI) m/z (%) 287 (1), 152 (4), 135 (100), 91 (34), 79
(44); HR-MS 287.0643 (C14H11O5N2 calcd 287.0668; C21H22O6N2-
C7H11O).
2-Decyl-2-m et h yl-4,5-b is(2-n it r op h en yl)[1,3]d ioxola n e
(5a ). Following the general procedure, the dodecan-2-one 4a (46
mg, 0.25 mmol) and the diol ((3) (91 mg, 0.3 mmol) in the
presence of PPTS (7 mg, 0.025 mmol) gave 5a (108 mg, 92%) as
a pale yellow oil: TLC Rf 0.55 (cyclohexane/AcOEt 3/1); IR
1
(CHCl3) νmax 2930, 2855, 1525, 1350 cm-1; H NMR (400 MHz,
CDCl3) δ 0.88 (t, J ) 6.8 Hz, 3 H), 1.20-1.40 (m, 14 H), 1.58 (m,
2 H), 1.66 (s, 3 H), 1.94 (m, 2 H), 5.46 (ab, J ab ) 8.1 Hz, 2 H),
7.48 (m, 2 H), 7.73 (t, J ) 7.6 Hz, 2 H), 7.79 (d, J ) 8.3 Hz, 2 H),
7.97 (td, J ) 8.1, 1.3 Hz, 2 H); 13C NMR (100 MHz, CDCl3) 14.1,
22.7, 24.2, 25.0, 29.3, 29.5, 29.6, 29.9, 31.9, 40.4, 79.4, 80.2, 111.4,
124.2, 128.9, 129.0, 129.1, 131.9, 132.3, 133.4, 148.9; MS (EI)
m/z (%) 329 (35), 152 (11), 135 (100), 104 (15), 91 (40); HR-MS
329.0782 (C16H13O6N2 calcd 329.0774; C26H34O6N2-C10H21).
2,3-B i s (2-n i t r o p h e n y l)-1,4-d i o x a -s p i r o [4.11]h e x a -
d eca n e (5b). Following the general procedure, the cyclodode-
canone 4b (182 mg, 1 mmol) and the diol ((3) (304 mg, 1 mmol)
in the presence of PPTS (25 mg, 0.1 mmol) gave 5b (350 mg,
75%) as a white solid: mp 153-154 °C; TLC Rf 0.45 (cyclohex-
ane/AcOEt 5%); IR (CHCl3) νmax 3020, 2935, 2850, 1525, 1470,
1360, 1220, 1115 cm-1; UV (MeCN) λmax (ꢀ) 210 (20300), 252
4-Ch olesten -3-on e, (1R,2R)-1,2-Bis(2-n itr oph en yl)eth an e-
1,2-d iol Keta l (5g). The 4-cholesten-3-one 4g (58 mg, 0.15
mmol), the diol (-)-3 (46 mg, 0.15 mmol), and PPTS (4 mg, 0.015
mmol) were stirred at 80 °C in dry benzene with molecular sieves
4 Å (at 110 °C in dry toluene only the deconjugated product was
observed). The organic phase was washed once with a satd
NaHCO3 solution and once with brine, dried over MgSO4,
filtered, and evaporated. The purification by FC (cyclohexane/
1
(7500); H NMR (400 MHz, CDCl3) δ 1.40 (m, 14 H), 1.60 (m, 4
AcOEt 9/1) gave 5g (68 mg, 67%) as a thick orange oil: [R]17
D
H), 1.98 (m, 4 H), 5.46 (s, 2 H), 7.47 (td, J ) 8.0, 1.3 Hz, 2 H),
7.72 (td, J ) 7.8, 1.3 Hz, 2 H), 7.78 (dd, J ) 8.3, 1.3 Hz, 2 H),
7.95 (dd, J ) 8.1, 1.3 Hz, 2 H); 13C NMR (100 MHz, CDCl3) 20.1,
22.2, 22.5, 25.8, 26.2, 33.4, 79.7, 114.1, 124.2, 129.0, 129.1, 132.0,
133.4, 149.0; MS (EI) m/z (%) 468 (1, M+•), 300 (1), 254 (3), 237
(5), 181 (3), 135 (100), 120 (13); HR-MS 300.1962 (C19H26O2N
calcd 300.1963).
+158.3 (8.7 mg‚mL-1, CHCl3); TLC Rf 0.48 (cyclohexane/AcOEt
3/1); IR (CHCl3) νmax 3025, 2950, 2870, 1705, 1655, 1610, 1580,
1525, 1465, 1350, 1100, 1010 cm-1; 1H NMR (400 MHz, CDCl3)
δ 0.70 (s, 3 H), 0.85-2.35 (m, 40 H), 5.55 (s, 2 H), 5.62 (s, 1 H),
7.47 (m, 2 H), 7.70-7.80 (m, 4 H), 7.96 (dd, J ) 7.1, 1.0 Hz, 1
H), 8.05 (d, J ) 7.0 Hz,1 H); 13C NMR (125 MHz, CDCl3)
12.0, 17.9, 18.6, 21.2, 22.5, 22.8, 23.8, 24.2, 28.0, 28.2, 28.9, 31.7,
32.3, 32.6, 34.2, 35.7, 35.8, 36.1, 38.7, 39.5, 39.8, 42.5, 53.4,
56.0, 56.1, 68.2, 79.7, 80.1, 107.4, 119.6, 124.2, 124.3, 128.8,
129.0, 129.1, 130.9, 132.3, 132.5, 133.4, 133.5, 148.9, 149.0, 153.5;
MS (EI) m/z (%) 491 (1), 400 (26), 384 (44), 369 (9), 342 (17),
271 (13), 261 (23), 247 (22), 229 (47), 124 (83), 93 (65), 55
(100); HR-MS 384.3378 (C27H44O calcd 384.3392; C41H54O6N2-
4,5-Bis(2-n itr op h en yl)-2-u n d ecyl[1,3]d ioxola n e (5c). Fol-
lowing the general procedure, the lauraldehyde 4c (92 mg, 0.5
mmol) and the diol ((3) (182 mg, 0.6 mmol) in the presence of
PPTS (12.5 mg, 0.05 mmol) gave 5c (210 mg, 90%) as a pale
yellow solid: mp 49-50 °C; TLC Rf 0.54 (cyclohexane/AcOEt 3/1);
IR (CHCl3) νmax 2930, 2855, 1530, 1350, 1265, 1205, 1140, 1035
cm-1 1H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 6.8 Hz, 3 H),
;
C
14H10O5N2).
1.20-1.40 (m, 16 H), 1.56 (m, 2 H), 1.92 (m, 2 H), 5.48 (t, J )
4.6 Hz, 1 H), 5.61 (ab, J ab ) 6.6 Hz, 2 H), 7.50 (m, 2 H), 7.72 (m,
Gen er a l P r oced u r e for th e P h otoch em ica l Dep r otec-
tion . The acetal (0.1 mmol) and an internal standard (tetrade-
1140 J . Org. Chem., Vol. 68, No. 3, 2003

cane) were dissolved in 10 mL of CH3CN or Et2O in a quartz
vessel. The mixture was degassed by bubbling argon and stirred
under irradiation at 350 nm for 1-2 h in a Rayonet apparatus
(equipped with 16 RPR-3500 Å monochromatic lamps). Aliquots
were taken after a given time and the yield was determined by
GC or NMR. The solvent was evaporated and the residue was
purified by FC (silica gel, cyclohexane/AcOEt).
Gen er a l P r oced u r e for Testin g th e Sta bility of Keta ls.
Samples of ketal 5b (47 mg, 0.1 mmol) were submitted to the
conditions described in the tables in a parallel reactor. The
residues were analyzed by NMR after workup (in some cases
after FC: silica gel, cyclohexane/AcOEt).
Ack n ow led gm en t. This work was supported by the
Swiss National Science Foundation (grant 20-65047.01)
and by the Fonds Fre´de´ric Firmenich et Philippe Chuit.
The authors thank Prof. Alexandre Alexakis for his
generous support.
Su p p or tin g In for m a tion Ava ila ble: Proton and carbon
NMR spectra for all cited compounds and chiral SFC data for
the diol 3. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O026347X
J . Org. Chem, Vol. 68, No. 3, 2003 1141