Pentadienylnitrobenzyl and Pentadienylnitropiperonyl Photochemically Removable Protecting Groups

Article abstract of DOI:10.1021/jo982383d

New photochemically removable protecting groups have been developed based on classical nitrobenzyl compounds modified by the inclusion of a pentadienyl group. It serves to trap through an internal Diels-Alder reaction the nitroso group produced as part of the photochemical deprotection process, preventing its further photochemistry or chemical reactions with nucleophiles.

Full text of DOI:10.1021/jo982383d

5042
J . Org. Chem. 1999, 64, 5042-5047
P en ta d ien yln itr oben zyl a n d P en ta d ien yln itr op ip er on yl
P h otoch em ica lly Rem ova ble P r otectin g Gr ou p s
Michael C. Pirrung,* Yong Rok Lee, Kaapjoo Park, and J ames B. Springer
Department of Chemistry, Levine Science Research Center, Duke University,
Durham, North Carolina 27708-0317
Received December 4, 1998
New photochemically removable protecting groups have been developed based on classical
nitrobenzyl compounds modified by the inclusion of a pentadienyl group. It serves to trap through
an internal Diels-Alder reaction the nitroso group produced as part of the photochemical
deprotection process, preventing its further photochemistry or chemical reactions with nucleophiles.
In tr od u ction
phates10 but have also aimed to develop more general
photoremovable groups through improvements in the
nitrobenzyl series. In short, a simple means to rapidly
inactivate the nitroso group was needed. This report
describes a solution to the problem of nitrobenzyl reactiv-
ity by trapping the product nitrosocompound as an
internal hetero-Diels-Alder adduct.
The concept of trapping the nitroso compound is not
new, and in many studies a high concentration of thiol
has been included for this purpose, though some biologi-
cal systems are incompatible with these conditions.11 The
hetero-Diels-Alder reaction of aryl nitroso compounds
such as nitrosobenzene with butadienes is well-known,12
but its bimolecular rate is far too slow to compete with
the photochemical and polar reactions of the nitrosoare-
ne.13 The intramolecular hetero-Diels-Alder reaction was
considered because this trapping reaction should be much
faster, but a potential concern was interference by the
diene with the photochemistry. Early mechanistic work
on the nitrobenzyl deprotection reaction suggested that
it is a singlet process and therefore would not be affected.
Danishefsky’s results14 gave further encouragement to
this thought. However, one study showed that deprotec-
tion of a nitrobenzyl ether includes a short-lived triplet
biradical that can be quenched by a cyclohexadiene.15
Nitrobenzyl alcohol derivatives are among the best-
known photochemically removable protecting groups.1
They play an important role in a variety of technologies,
including photolithography2 and time-resolved studies in
a variety of disciplines.3,4 The kinetics and mechanism
by which their photoremoval occurs have been exten-
sively studied.5 On UV irradiation, they undergo a net
internal redox process, releasing the heteroatom and
producing an intrinsically reactive o-nitrosocarbonyl
compound, which has several drawbacks. The nitroso
compound can act as an internal filter and has a
photochemistry of its own6 that can lead to other even
more intensely absorbing materials, such as azo and
azoxy compounds. It is often reactive with sensitive
functionalities, particularly nucleophiles such as thiols7
and amines, and can therefore be injurious8 to the living
systems in which nitrobenzyl groups are often used.
Nitrobenzyl compounds have been used in the protection
or “caging” of a variety of biomolecules despite these
shortcomings,1,9 but it is clear that wider application of
the concept would be possible were superior photochemi-
cally removable groups available. We have developed
novel groups for the protection of alcohols and phos-
(1) Pillai, V. N. R. Synthesis 1980, 1-26.
Resu lts
(2) Sabongi, G. J . Chemical Triggering; Plenum: New York, 1987.
(3) Adams, S. R.; Kao, J . P. Y.; Tsien, R. Y. J . Am. Chem. Soc. 1989,
111, 7957-7968. Adams, S. R.; Tsien, R. Y. Annu. Rev. Physiol. 1993,
55, 755-784. Photochemical Probes in Biochemistry; Nielsen, P. E.,
Ed.; Kluwer: New York, 1989. Walker, J . W.; Reid, G. P.; McCray, J .
A.; Trentham, D. R. J . Am. Chem. Soc. 1988, 110, 7170-7177.
Biological Applications of Photochemical Switches; Morrison, H., Ed.;
Wiley: New York, 1993.
For initial evaluation of the approach, an unsubstituted
aromatic ring was used because electron-donating groups
(10) Pirrung, M. C.; Lee, Y. R. J . Org. Chem. 1993, 58, 6961. Pirrung,
M. C.; Shuey, S. W. J . Org. Chem. 1994, 59, 3890. Pirrung, M. C.;
Bradley, J .-C. J . Org. Chem. 1995, 60, 1116.
(11) Goldman, Y. E.; Hibberd, M. G.; Trentham, D. R. J . Physiol.
1984, 354, 577.
(12) Hamer, J .; Ahmad, M.; Holliday, R. E. J . Org. Chem. 1963, 28,
3034-3036.
(13) Ludwig, R.; Pirrung, M. C. Unpublished results.
(14) McClure, K. F.; Benbow, J . W.; Danishefsky, S. J .; Schulte, G.
K. J . Am. Chem. Soc. 1991, 113, 8185-8186. McClure, K. F.; Benbow,
J . W.; Danishefsky, S. J .; Schulte, G. K. J . Am. Chem. Soc. 1993, 115,
12305-12314.
(15) Yip, R. W.; Wen, Y. X.; Gravel, D.; Giasson, R.; Sharma, D. K.
J . Phys. Chem. 1991, 95, 6078-6081.
(4) Schlichting, I.; Rapp, G.; J ohn, J .; Wittinghofer, A.; Pai, E. F.;
Goody, R. S. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 7687-7690.
(5) McCray, J . A.; Trentham, D. R. Annu. Rev. Biophys. Biophys.
Chem. 1989, 18, 239-270. Walker, J . W.; Reid, G. P.; McCray, J . A.;
Trentham, D. R. J . Am. Chem. Soc. 1988, 110, 7170-7177. Yip, R.
W.; Sharma, D. K.; Giasson, R.; Gravel, D. J . Phys. Chem. 1984, 88,
5770-5772; 1985, 89, 5328-5330. Yip, R. W.; Wen, Y. X.; Gravel, D.;
Giasson R.; Sharma, D. K. J . Phys. Chem. 1991, 95, 6078-6081.
Schupp, H.; Wong, W. K.; Schnabel, W. J . Photochem. 1987, 36, 85-
97. Reichmanis, E.; Smith, B. C.; Gooden, R. J . Polym. Sci., Polym.
Chem. Ed. 1985, 23, 1-8.
(6) Tomioka, H.; Ickikawa, N.; Komatsu, K. J . Am. Chem. Soc. 1992,
114, 8045-8053.
(16) Compound 3a was obtained as a mixture of diastereomers that
apparently results from photochemical equilibration of the diene before
deprotection. In one case, interruption of a reaction and reisolation of
starting material showed it was an (E,E)/(E,Z) mixture.
(17) Tsunoda, T.; Yamamiya, Y.; Ito, S. Tetrahedron Lett. 1993, 34,
1639-1642.
(7) Kaplan, J . Biochemistry 1978, 17, 1929-1935.
(8) Kazanis, S.; McClelland, R. A. J . Am. Chem. Soc. 1992, 114,
3052-3059.
(9) Patchornik, A.; Amit, B.; Woodward, R. B. J . Am. Chem. Soc.
1970, 92, 6333-6335. Pillai, V. N. R. In Organic Photochemistry;
Padwa, A., Ed.; Marcel Dekker, Inc.: New York, Basel, 1987; Vol. 9,
Chapter 3, pp 225-323.
(18) Cummings, R. T.; Krafft, G. A. Tetrahedron Lett. 1988, 29, 65-
68.
10.1021/jo982383d CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/17/1999

PeNB and PeNP Photochemically Removable Protecting Groups
J . Org. Chem., Vol. 64, No. 14, 1999 5043
these reactions, though generally in somewhat lower
yield (∼60%) than in the irradiation of 2.
F igu r e 1. UV spectrum of the irradiation of 2 (1 mM, MeOH)
with an Oriel arc lamp source delivered through a liquid light
guide at times up to 6 min.
in the nitrosoarene slow cycloaddition.12 The synthesis
of pentadienylnitrobenzyl alcohol (PeNB-OH) was ac-
complished as shown in eq 1 (78%). To test the design,
Quantum yield studies were conducted with 2 using
nitrobenzyl alcohol (Φ ) 0.45)18 as an actinometer and
following loss of starting material from 5 to 25% conver-
sion by NMR with an internal standard. The measured
quantum yield for 2 is 0.26. Quantum yields measured
in the same way against nitrobenzyl cyclohexyl carbam-
ate (Φ ) 0.07)18 for the derivatives of 2 are as follows:
4, 0.22; 5, 0.41; 7, 0.38. Rate studies of the benzyl and
hexyl ethers were conducted using a 83 mW/cm2 350 nm
broad-band source, following the reaction by GC with
internal standards. Both give 5 min half-lives.
Success with this first group encouraged preparation
and study of an analogue incorporating a red-shifting
methylenedioxy group. An aldol approach (eq 2) was used
in this case to produce pentadienylnitropiperonyl alcohol
(12, PeNP-OH) (50%). It provides 3b on Hanovia irradia-
compound 2 was irradiated (10 mM in MeOH) with a 450
W Hanovia light source equipped with a water-cooled
quartz immersion well to provide within 3 h the expected
3a 16 as a barely separable mixture of diastereomers in
79% isolated yield, based on recovered starting material.
These compounds were extensively characterized by
spectroscopic means, including 2D NMR, to establish the
regiochemistry as indicated, and hydrogenated (Pt/C) to
a more readily separable mixture of dihydro derivatives.
These compounds undergo interconversion in solution
and deuterium exchange R to the ketone. The reaction
to form 3a gives an isosbestic point at 305 nm when
followed by UV (Figure 1), showing that it is clean at low
conversion. Eight derivatives 4-11, encompassing some
common functional groups (carboxylic acid, amine, alco-
hol, and phenol) that would be desirable to protect, were
efficiently prepared from 2 by conventional routes (see
the Experimental Section: esters from acid chlorides,
aliphatic ethers from halides, aryl ethers via the Mit-
sunobu reaction under improved conditions,17 carbamates
from isocyanates). Protection reactions of 2 are limited
to neutral or basic conditions because its benzylic/allylic
character makes it somewhat acid-sensitive. Photochemi-
cal deprotection reactions (10 mM in MeOH) were
conducted on a 0.2 mmol scale for 1.5-2 h at 254 nm for
these PeNB derivatives, except for the phenyl ether,
which required 4 h. Yields are given below each reactant.
Compound 3a was naturally also obtained in each of
tion in ∼80% yield. Simultaneous irradiation of 2 and
12 in the Hanovia apparatus shows a half-time for the
conversion of the former to 3a of 30 min, while the
conversion of the latter to 3b has a half-time of 10 min,
at least partially related to its greater absorption at 350
nm. The effectiveness of 12 as a protecting group was
also demonstrated with ether and ester derivatives 13-
16. Deprotection reactions of these PeNP derivatives
were performed at 350 nm for 3 h, except for the phenyl
ether, which required 254 nm irradiation. The differing
behavior of the phenyl derivatives may be related to
energy transfer or competitive absorption. Again, the
yields of deprotection reactions are given below each
reactant.
Discu ssion a n d Con clu sion
This work offers a novel strategy for the spatially and
temporally controlled release of common functional groups

5044 J . Org. Chem., Vol. 64, No. 14, 1999
Pirrung et al.
1
cm-1. H NMR (CDCl3): δ 7.92 (1H, d, J ) 8 Hz), 7.78 (1H, d,
J ) 8 Hz), 7.63 (1H, t, J ) 8 Hz), 7.43 (1H, t, J ) 8 Hz), 6.35
(1H, dd, J ) 10.0, 15.0 Hz), 6.04 (1H, m), 5.8 (3H, m), 2.45
(1H, d, J ) 3.2 Hz), 1.75 (3H, d, J ) 6.5 Hz). 13C NMR
(CDCl3): δ 138.0, 133.4, 132.1, 131.5, 130.3, 129.7, 128.6, 128.3,
128.2, 124.5, 69.7, 18.2. UV: λmax 264 nm, ꢀ ) 5370 (CH3CN).
Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found:
C, 65.46; H, 5.94; N, 6.35. HRMS (FAB, M+): calcd for C12H13
NO3 219.0895, found 219.0896.
-
P h otocycloaddu ct 3a. Pentadienylnitrobenzyl alcohol (62.2
mg, 0.284 mmol) was dissolved in dry CH3OH (28 mL) in a
tightly capped Pyrex flask. The solution was irradiated while
stirring without temperature control for 4 h using a 450 W
Hanovia light source equipped with a water-cooled quartz
immersion well. The CH3OH was evaporated, and the residue
was rotary chromatographed on a 1 mm silica plate utilizing
1:5 ethyl acetate/hexanes to elute 3a (33.2 mg, 58%) as a 1:1
mixture of diastereomers. Some pentadienylnitrobenzyl alcohol
(12.9 mg, 21%) was recovered as well. IR (KBr): 3343 (-OH,
enol tautomer), 3071, 2975, 2926, 2873, 2245, 1713 (CdO, keto
tautomer), 1613, 1485, 1469, 1320, 1155, 1102, 1050, 938, 901,
that does not produce a reactive byproduct or require
additives. The reactions are clean and efficient in both
the chemical and quantum sense, and they occur rapidly.
The protected derivatives can be made through straight-
forward, traditional transformations, and in fact, the use
of the Mitsunobu reaction should greatly expand the
range of functional groups (imides, heterocycles, thiols)
that can be readily protected. A disadvantage of these
groups is their acid sensitivity, more so for 12. The
irradiation wavelengths are in open spectral windows (for
biological systems). It is interesting that the intramo-
lecular hetero-Diels-Alder cycloaddition process is so
finely balanced, as analogues of 2 having zero or two
terminal diene methyl groups do not undergo clean
photochemical reaction to afford a cycloadduct, and
Danishefsky obtained a cycloadduct in good yield from a
dienone with an R-methoxy group but no terminal
substitution.14
747, 687 cm-1 1H NMR (CDCl3): δ 7.53 (2H, d, J ) 8 Hz),
.
7.42 (2H, t, J ) 8 Hz), 6.79 (2H, t, J ) 8 Hz), 6.73 (2H, d, J )
8 Hz), 6.29 (2H, t, J ) 6.6 Hz), 5.53 (2H, dd, J ) 5.6, 13.6 Hz),
5.14 (4H, m), 4.83 (2H, d, J ) 5.6 Hz), 1.42 (3H, d, J ) 6.5
Hz), 1.34 (3H, d, J ) 6.5 Hz). 13C NMR (CDCl3): δ 198.8, 198.6,
159.22, 159.17, 138.9, 138.7, 138.00, 137.97, 125.3 (two car-
bons), 124.7, 124.4, 119.87, 119.77, 118.9, 118.8, 112.05,
112.03, 101.1, 100.8, 82.8, 82.6, 22.3, 22.2. UV: λmax 256 nm,
ꢀ ) 5802 (CH3CN). HRMS (FAB, M+): calcd for C12H11NO2
201.0789, found 201.0782.
Hyd r ogen a tion of 3a . Five percent Pt on activated carbon
(43 mg) was weighed into a flame-dried flask, and the
photoadduct 3a (25 mg, 0.124 mmol) was added as a solution
in 0.5 mL of dry THF at room temperature. Triethylamine (2.5
mL, 0.018 mmol) was added, and the resulting mixture was
subjected to 15 cycles of evacuating the flask enough to boil
the THF and then releasing the vacuum to a H2-filled balloon.
The resulting H2-saturated solution was stirred overnight at
room temperature. The mixture was filtered through a pad of
Celite, and the residue was purified by radial chromatography
using 30% ethyl acetate in hexanes to afford the expected
compounds as a 1:1 mixture of diastereomers (15.5 mg, 61%).
The higher Rf (twice-developed 25% EtOAC in hexanes)
Exp er im en ta l Section
All reagents were purchased from Aldrich unless otherwise
indicated and were verified and/or titrated before use. 3,4-
Methylenedioxyacetophenone was purchased from Lancaster
Synthesis. Diethyl ether and THF were distilled from sodium/
benzophenone immediately prior to use. Triethylamine and
diisopropylamine were distilled from sodium and stored under
argon. Acetonitrile, pyridine, benzene, and dichloromethane
were freshly distilled from calcium hydride. Methanol was
distilled from magnesium turnings immediately prior to use.
All reactions were performed in oven-dried glassware under
argon atmosphere unless otherwise noted. Flash column
chromatography was carried out on EM Reagents silica gel
60 (230-400 mesh). Silica gel was deactivated by forming a
slurry in 10% triethylamine in hexanes, filtering, and washing
with copious amounts of hexanes. Capillary gas chromatog-
raphy was performed with a 0.25 mm i.d. × 30 m DB-5.625
column. Melting points are uncorrected. 1H NMR spectra were
obtained on 300 or 400 MHz spectrometers. Broad-band
irradiations were performed using a 450 W Hanovia light
source equipped with a water-cooled quartz immersion well
or a Rayonet photochemical reactor containing 16 phosphor-
coated 350 nm lamps or 254 nm lamps. All single wavelength
irradiations were performed using an Oriel light source.
Elemental analyses were performed by Atlantic Microlabs.
1-(2-Nitr oph en yl)-2,4-h exadien -1-ol (2). 2-Bromonitroben-
zene (100 mg, 0.495 mmol) was dissolved in THF (5.5 mL),
and the solution was cooled to -78 °C. A 1.8 M ether/hexane
solution of phenyllithium (0.33 mL, 0.59 mmol) was added
dropwise. This deep purple solution was stirred at -78 °C for
1.25 h, and then 2,4-hexadienal (82 µL, 0.74 mmol) was added
dropwise. The reaction was stirred at -78 °C for 30 min and
was allowed to warm to room temperature over another 15
min. Water was added carefully, and the mixture was ex-
tracted with ethyl acetate. The combined extracts were dried
(MgSO4) and evaporated; the residue was purified by flash
chromatography using 5% ethyl acetate in hexanes as eluent
to afford pure 1-(2-nitrophenyl)-2,4-hexadien-1-ol (84.4 mg,
78%) as a peach-colored solid. Mp: 70-71 °C. IR (CH2Cl2):
3587, 3440, 3057, 3022, 2924, 1658, 1609, 1529, 1356, 993, 857
1
compound gave the following data. H NMR (CDCl3): δ 7.53
(1H, d, J ) 8 Hz), 7.42 (1H, t, J ) 8 Hz), 6.82 (1H, t, J ) 8
Hz), 6.75 (1H, d, J ) 8 Hz), 4.75 (1H, bs), 4.41 (1H, m), 2.35
(2H, m), 2.04 (1H, m), 1.66 (1H, m), 1.34 (3H, d, J ) 6.5 Hz).
The lower Rf compound gave the following data. 1H NMR
(CDCl3): δ 7.56 (1H, d, J ) 8 Hz), 7.42 (1H, t, J ) 8 Hz), 6.82
(1H, t, J ) 8 Hz), 6.75 (1H, d, J ) 8 Hz), 4.75 (1H, bs), 4.41
(1H, m), 2.36 (2H, m), 2.20 (1H, m), 2.00 (1H, m), 1.34 (3H, d,
J ) 6.5 Hz). The separated diastereomers were equilibrated
to the original 1:1 diastereomeric mixture by allowing them
to stand in CH2Cl2 solution overnight at room temperature. A
1:1 mixture of the diastereomers was stirred with D2O, and
the broad singlet at 4.75 disappeared from the 1H NMR
spectrum.
3b. Yield: 75% at 80% conversion. IR (CH2Cl2): 3358, 3080,
2976, 2905, 1697, 1618, 1485, 1302, 1063, 939, 910, 862, 833
cm-1. 1H NMR (CDCl3): δ 6.91 (2H, s), 6.30 (2H, m), 6.27 (2H,
s), 5.97 (4H, s), 5.56 (2H, ddd, J ) 12.6, 5.8, 2.0 Hz), 5.17 (2H,
m), 4.81 (2H, bd, J ) 8.7 Hz), 1.45 (3H, d, J ) 6.5 Hz), 1.37
(3H, d, J ) 6.5 Hz). 13C NMR (CDCl3): δ 196.3, 196.1, 158.7,
158.6, 157.03, 156.99, 144.2, 142.8, 142.7, 138.5, 138.4, 124.9,
124.6, 111.6, 111.5, 111.3, 102.6 (2 carbons), 101.99, 101.96,
93.30, 93.27, 82.9, 82.8, 22.24, 22.20. UV: λmax 279 nm, ꢀ 9638
(CH3CN). HRMS (FAB, M+): calcd for C13H11NO4 245.0688,
found 245.0690.
1-(Ben zoyloxy)-1-(2-n itr op h en yl)-2,4-h exa d ien e (4). A
mixture of 1-(2-nitrophenyl)-2,4-hexadien-1-ol (50.1 mg, 0.229
mmol) and 4-(dimethylamino)pyridine (4.2 mg, 0.034 mmol)
was dissolved in dry CH2Cl2 (1.0 mL), and pyridine (50 µL,
0.62 mmol) was added in one portion. The solution was cooled
to 0 °C, and benzoyl chloride (40 µL, 0.34 mmol) was added

PeNB and PeNP Photochemically Removable Protecting Groups
J . Org. Chem., Vol. 64, No. 14, 1999 5045
dropwise. The reaction was allowed to warm to room temper-
ature while being stirred overnight and then diluted with ethyl
acetate (20 mL). The turbid mixture was washed with water
and saturated aqueous CuSO4 solution. The organic phase was
dried (MgSO4) and concentrated; the residue was purified by
flash column chromatography using deactivated silica gel and
5% ethyl acetate in hexanes as eluent to afford pure 1-(ben-
zoyloxy)-1-(2-nitrophenyl)-2,4-hexadiene (63.7 mg, 86%) as a
yellow gum. IR (KBr): 3068, 3025, 2963, 2915, 2853, 1722,
1658, 1605, 1580, 1529, 1450, 1353, 1262, 1101, 1069, 990, 713
cm-1. 1H NMR (CDCl3): δ 8.08 (2H, m), 7.97 (1H, m), 7.73 (1H,
m), 7.60 (2H, m), 7.46 (2H, m), 7.08 (1H, d, J ) 6.7 Hz), 6.39
(1H, dd, J ) 10.5, 15.3 Hz), 6.08 (1H, m), 5.84 (3H, m), 1.77
(3H, d, J ) 6.7 Hz). 13C NMR (CDCl3): δ 165.1, 147.9, 135.2,
134.2, 133.5, 133.2, 132.5, 130.2, 129.7, 129.6, 128.6, 128.4,
128.12, 128.08, 124.6, 71.8, 18.2. Anal. Calcd for C19H17NO4:
C, 70.58; H, 5.30; N, 4.33. Found: C, 70.51; H, 5.33; N, 4.27.
to ascertain the concentration of PhCH2OH in solution and
thus the percentage yield of deprotection (GC oven tempera-
ture ) 100 °C, isothermal). Analogous response factor analyses
were performed for 6 utilizing internal standards and GC
conditions tailored for the substrate to be analyzed.
internal
GC oven
R
t1/2 (min)
% yield
standard
temp (°C)
benzyl
n-hexyl
5
5
100 ( 7
79 ( 4
n-octanol
cyclohexanol
100
70
1-(Cycloh exylcar bam oyloxy)-1-(2-n itr oph en yl)-2,4-h exa-
d ien e (7). 1-(2-Nitrophenyl)-2,4-hexadien-1-ol (51.2 mg, 0.234
mmol) was dissolved in THF (2.2 mL), and the solution was
cooled to 0 °C. A 1.4 M solution of CH3Li in ether (16 µL, 0.022
mmol) was quickly added, and this solution was stirred at 0
°C for 15 min. Cyclohexyl isocyanate (58 µL, 0.45 mmol) was
added dropwise, and the reaction was stirred for 30 min. The
reaction was quenched with the addition of water, and the
mixture was extracted with ethyl acetate. The ethyl acetate
was dried (MgSO4) and evaporated, and the residue was
purified by flash chromatography using deactivated silica gel
and 5% ethyl acetate in hexanes as eluent to afford pure
1-(cyclohexylcarbamoyl)-1-(2-nitrophenyl)-2,4-hexadiene (67.9
mg, 84%) as an amber gum. IR (KBr): 3405, 3328, 3023, 2930,
2856, 2251, 1711 (CdO), 1522, 1449, 1352, 1313, 1252, 1225,
1-Ben zyloxy-1-(2-n itr op h en yl)-2,4-h exa d ien e (5). 1-(2-
Nitrophenyl)-2,4-hexadien-1-ol (50.2 mg, 0.229 mmol) and
Ag2O (123.8 mg, 0.534 mmol) were dissolved in dry DMF (1.0
mL). Benzyl bromide (82 µL, 0.69 mmol) was added in one
portion, and the brown suspension was stirred at room
temperature for 7 h. The mixture was vacuum filtered, and
the cake was washed with ether (10 mL). The filtrate was
combined with additional ether (40 mL), and the solution was
washed with water, dried (MgSO4), and evaporated; the
residue was purified by preparative TLC using 5% ethyl
acetate in hexanes to afford pure 1-benzyloxy-1-(2-nitrophen-
yl)-2,4-hexadiene (58.6 mg, 83%) as a pale oil. IR (KBr): 3065,
3026, 2914, 2862, 1659, 1607, 1528, 1452, 1353, 1070, 991, 742,
1
1031, 990, 735 cm-1. H NMR (CDCl3): δ 7.91 (1H, d, J ) 8.0
Hz), 7.62 (2H, m), 7.41 (1H, m), 6.73 (1H, d, J ) 6.6 Hz), 6.28
(1H, dd, J ) 10.4, 15.3 Hz), 6.02 (1H, m), 5.74 (2H, m), 4.75
(1H, d, J ) 7.9 Hz), 3.43 (1H, m), 1.93 (2H, m), 1.74 (3H, d, J
) 6.8 Hz), 1.65 (2H, m), 1.0-1.4 (6H, m). 13C NMR (CDCl3):
δ 154.1, 147.8, 135.9, 133.5, 133.2, 131.9, 130.3, 128.2, 128.0,
126.7, 124.4, 71.4, 49.9, 33.2, 25.3, 24.7, 18.1. Anal. Calcd for
695 cm-1 1H NMR (CDCl3): δ 7.87 (1H, d, J ) 8 Hz), 7.80
.
(1H, d, J ) 8 Hz), 7.61 (1H, t, J ) 8 Hz), 7.2-7.5 (6H, m), 6.33
(1H, dd, J ) 10.4, 15.0 Hz), 6.05 (1H, m), 5.5-5.8 (3H, m),
4.54 (1H, d, J ) 11.4 Hz), 4.44 (1H, d, J ) 11.4 Hz), 1.75 (3H,
d, J ) 6.7 Hz). 13C NMR (CDCl3): δ 148.5, 137.7, 136.7, 133.3,
133.2, 131.4, 130.5, 128.5, 128.3, 128.2, 128.10, 128.08, 127.6,
124.2, 76.6, 70.8, 18.1. Anal. Calcd for C19H19NO3: C, 73.77;
H, 6.19; N, 4.53. Found: C, 73.93; H, 6.24; N, 4.43.
C
19H24N2O4: C, 66.26; H, 7.02; N, 8.13. Found: C, 66.19; H,
7.06; N, 8.03.
1-(2-P h en ylacetoxy)-1-(2-n itr oph en yl)-2,4-h exadien e (8).
A mixture of 1-(2-nitrophenyl)-2,4-hexadien-1-ol (500 mg, 2.28
mmol) and 4-(dimethylamino)pyridine (28 mg, 0.228 mmol)
was dissolved in dry CH2Cl2 (10 mL), and pyridine (0.55 mL,
6.84 mmol) was added. The solution was cooled to 0 °C, and
phenylacetyl chloride (0.60 mL, 4.56 mmol) was added drop-
wise. The reaction was stirred for 20 min at 0 °C and then
allowed to warm to room temperature while stirring overnight.
The reaction mixture was diluted with water and extracted
with CH2Cl2. The organic phase was washed with saturated
aqueous CuSO4 solution and brine, dried (Na2SO4), and
concentrated. The residue was purified by flash column
chromatography using deactivated silica gel and 5% ethyl
acetate in hexanes (containing 2% NEt3) as eluent to afford
pure 1-(2-phenylacetoxy)-1-(2-nitrophenyl)-2,4-hexadiene (684
mg, 89%) as a pale orange oil. IR (neat): 3027, 2922, 1742
(CdO), 1530, 1352, 1245, 1139 cm-1. 1H NMR (CDCl3): δ 7.91
(1H, ddd, J ) 8.0, 1.6, 0.8 Hz), 7.50 (1H, m), 7.40 (2H, m),
7.28 (5H, m), 6.84 (1H, d, J ) 6.4 Hz), 6.21 (1H, dd, J ) 15.2,
10.4 Hz), 6.00 (1H, m), 5.74 (1H, dd, J ) 14.8, 6.4 Hz), 5.68
(1H, dd, J ) 15.2, 6.4 Hz), 3.66 (2H, s), 1.73 (3H, d, J ) 6.4
Hz). 13C NMR (CDCl3): δ 169.8, 147.7, 134.9, 133.8, 133.4,
133.2, 132.1, 130.1, 129.1, 128.43, 128.41, 128.37, 128.3, 127.9,
127.0, 125.8, 124.3, 71.3, 41.2, 18.0. HRMS (FAB, [M + H]+):
calcd for C20H20NO4 338.1392, found 338.1382 (this compound
contains an inseparable minor olefin stereoisomer (6%)).
1-P h en oxy-1-(2-n itr op h en yl)-2,4-h exa d ien e (9). Tribu-
tylphosphine (0.85 mL, 3.42 mmol) was added to a solution of
1-(2-nitrophenyl)-2,4-hexadien-1-ol (500 mg, 2.28 mmol) and
phenol (322 mg, 3.42 mmol) in dry benzene (15 mL) at 0 °C.
1,1′-(Azodicarbonyl)dipiperidine (863 mg, 3.42 mmol) was
added to the solution with stirring. After 10 min, the reaction
mixture was allowed to warm to room temperature and stirred
for 20 h. Hexane was added, and the mixture was filtered
through Celite. The solvent was evaporated, and the residue
was purified by flash column chromatography using deacti-
vated silica gel and 2% ethyl acetate in hexanes (containing
2% NEt3) as eluent to afford 1-phenoxy-1-(2-nitrophenyl)-2,4-
hexadiene (410 mg, 61%) as a yellow oil. IR (neat): 3033, 2915,
2854, 1596, 1523, 1492, 1345, 1233 cm-1. 1H NMR (CDCl3): δ
1-(1-Hexyloxy)-1-(2-n itr op h en yl)-2,4-h exa d ien e (6). A
mixture of class IV KF/alumina reagent19 (189 mg, 1.2 mmol)
and 1-(2-nitrophenyl)-2,4-hexadien-1-ol (101.5 mg, 0.4630
mmol) was suspended in dry CH3CN (0.65 mL). Hexyl iodide
(104 µL, 0.705 mmol) was added in one portion, and the
reaction was stirred vigorously at room temperature for 10 h.
More hexyl iodide (104 µL, 0.705 mmol) and KF/alumina (195
mg, 1.3 mmol) were added, and the reaction was stirred
overnight. More KF/alumina (230 mg, 1.5 mmol) was added,
and the reaction was stirred for another 10 h. The mixture
was filtered, and the residue was washed with ethyl acetate.
The solvents were evaporated, and the residue was purified
by radial chromatography on a 1 mm silica plate using 1%
ether in hexanes to give pure 1-(1-hexyloxy)-1-(2-nitrophenyl)-
2,4-hexadiene (75.7 mg, 54%) as a pale yellow oil. IR (KBr):
3020, 2932, 2861, 1659, 1608, 1529, 1467, 1450, 1354, 1303,
1
1090, 890, 856 cm-1. H NMR (CDCl3): δ 7.86 (1H, d, J ) 8
Hz), 7.73 (1H, d, J ) 8 Hz), 7.60 (1H, t, J ) 8 Hz), 7.40 (1H,
t, J ) 8 Hz), 6.28 (1H, dd, J ) 10.4, 15.2 Hz), 6.03 (1H, m),
5.74 (1H, m), 5.61 (1H, m), 5.41 (1H, d, J ) 7.0 Hz), 3.46 (1H,
m), 3.31 (1H, m), 1.74 (3H, d, J ) 6.8 Hz), 1.57 (2H, m), 1.2-
1.4 (6H, m), 0.88 (3H, t, J ) 6.8 Hz). 13C NMR (CDCl3): δ
148.5, 137.2, 133.1, 132.8, 131.0, 130.6, 128.9, 128.4, 127.9,
124.1, 76.8, 69.3, 31.6, 29.7, 25.8, 22.6, 18.1, 14.0. HRMS (FAB,
M+): calcd for C18H25NO3 303.1834, found 303.1824.
Kin etics of P h otod ep r otection of P eNB Eth er s. A
0.0125 M stock solution of 5 in CH3OH (400 µL, 4.99 × 10-3
mmol) was placed in an oven-dried Pyrex vial, and a 0.0249
M solution of n-octanol in CH3OH (100 µL, 2.49 × 10-3 mmol)
was added as an internal GC standard. The solution was
irradiated using a 350 nm Oriel light source equipped with
an infrared filtering fiber optic cable, and 1 µL aliquots were
removed and injected into a capillary GC at timed intervals
(19) Ando, T.; Yamawaki, J .; Kawarte, T.; Sum, S.; Hanafusa, T.
Bull. Chem. Soc. J pn. 1982, 55, 2504-2507.

5046 J . Org. Chem., Vol. 64, No. 14, 1999
Pirrung et al.
7.89 (1H, dd, J ) 8.1, 0.9 Hz), 7.53 (2H, m), 7.38-7.23 (3H,
m), 7.13 (1H, dd, J ) 15.9, 1.2 Hz), 7.01-6.89 (3H, m), 6.23
(1H, dd, J ) 15.9, 6.0 Hz), 5.88 (1H, dqd, J ) 15.6, 6.6, 0.9
Hz), 5.65 (1H, ddd, J ) 15.6, 6.6, 1.5 Hz), 5.28 (1H, td, J )
6.6, 1.2 Hz), 1.75 (3H, ddd, J ) 6.6, 1.5, 0.9 Hz). 13C NMR
(CDCl3): δ 157.4, 147.6, 133.9, 132.9, 132.2, 129.4, 129.2 (2
carbons), 128.9, 128.6, 128.1, 126.8, 124.4, 120.9, 116.1 (2
acetate in hexanes to afford 3,4-methylenedioxy-6-nitroac-
etophenone (9.43 g, 74%). Mp: 119-120 °C (lit.20 mp 122-
123 °C).
1-(3,4-Meth ylen edioxy-6-n itr oph en yl)-3-h ydr oxy-4-h ex-
en -1-on e. 3,4-Methylenedioxy-6-nitroacetophenone (4.5 g, 21
mmol) was dissolved in dry CH2Cl2 (86 mL) cooled to 0 °C. A
1 M solution of dibutylboron triflate in CH2Cl2 (43.0 mL, 43.0
mmol) was added over 10 min, and the resulting orange/red
solution was stirred at 0 °C for an additional 10 min.
Diisopropylethylamine (8.20 mL, 47.07 mmol) was added over
3 min as a solution in 5 mL of CH2Cl2, and the resulting red/
brown solution was stirred at 0 °C for 30 min. The reaction
was allowed to warm to room temperature and was stirred an
additional 30 min. It was cooled to -78 °C, and crotonaldehyde
(4.22 mL, 50.9 mmol) was added over 10 min as a solution in
5 mL of CH2Cl2. This brown solution was stirred at -78 °C
for 20 min, warmed to 0 °C, and stirred for 2 h. The reaction
was quenched at 0 °C by the addition of pH 7 phosphate buffer
(172 mL), CH3OH (258 mL), and 30% H2O2 (172 mL), and this
mixture was stirred vigorously at room temperature for a few
min. The phases were separated, and the aqueous phase was
extracted with CH2Cl2. The combined extracts were washed
successively with saturated aqueous NH4Cl solution and
saturated aqueous NaCl solution. The CH2Cl2 solution was
dried (MgSO4) and evaporated to give 1-(3,4-methylenedioxy-
6-nitrophenyl)-3-hydroxy-4-hexen-1-one (6.97 g, 100%), which
carbons), 78.6, 17.9. HRMS (FAB, [M - H]+): calcd for C18H16
-
NO3 294.1130, found 294.1118 (this compound contains an
inseparable minor olefin stereoisomer (<8%)).
1-(1-Ger a n yloxy)-1-(2-n itr op h en yl)-2,4-h exa d ien e (10).
1-(2-Nitrophenyl)-2,4-hexadien-1-ol (500 mg, 2.28 mmol) was
dissolved in dry CH3CN (10 mL) at room temperature. Geranyl
bromide (0.54 mL, 2.74 mmol) and KF/alumina reagent (40%,
1.81 g, 11.4 mmol) were added in one portion. The reaction
mixture was stirred vigorously for 10 h at room temperature.
More geranyl bromide (0.54 mL, 2.74 mmol) and KF/alumina
reagent (40%, 1.81 g, 11.4 mmol) were added, and the reaction
was stirred overnight. The mixture was filtered through Celite,
and the filter cake was washed with ethyl acetate (50 mL).
The solvents were evaporated, and the residue was purified
by flash column chromatography using deactivated silica gel
and 2% ethyl acetate in hexanes (containing 2% NEt3) as
eluent to afford pure 1-(1-geranyloxy)-1-(2-nitrophenyl)-2,4-
hexadiene (705 mg, 87%) as an orange oil. IR (neat): 2971,
2929, 2855, 1535, 1444, 1358, 1052 cm-1. 1H NMR (CDCl3): δ
7.85 (1H, dd, J ) 8.0, 1.2 Hz), 7.76 (1H, dd, J ) 8.0, 1.2 Hz),
7.60 (1H, m), 7.39 (1H, m), 6.27 (1H, dd, J ) 15.2, 10.8 Hz),
6.01 (1H, m), 5.74 (1H, dd, J ) 14.8, 6.8 Hz), 5.62 (1H, dd, J
) 15.2, 6.8 Hz), 5.48 (1H, d, J ) 6.8 Hz), 5.34 (1H, m), 5.08
(1H, m), 4.01 (1H, dd, J ) 11.6, 6.8 Hz), 3.92 (1H, dd, J )
11.6, 6.8 Hz), 2.05 (4H, m), 1.74 (3H, dd, J ) 6.8, 1.2 Hz), 1.68
(3H, s), 1.59 (6H, d, J ) 8.8 Hz). 13C NMR (CDCl3): δ 148.4,
140.5, 136.9, 132.9, 132.7, 131.3, 130.7, 130.5, 128.8, 128.4,
127.8, 123.9, 123.8, 120.2, 75.4, 65.2, 39.4, 26.2, 25.5, 17.9, 17.5,
16.2. HRMS (FAB, [M - H]+): calcd for C22H28NO3 354.2069,
found 354.2061 (this compound contains an inseparable minor
olefin stereoisomer (<13%)).
1-(An isylca r ba m oyloxy)-1-(2-n itr op h en yl)-2,4-h exa d i-
en e (11). 1-(2-Nitrophenyl)-2,4-hexadien-1-ol (250 mg, 1.14
mmol) was dissolved in dry THF (5 mL), and the solution was
cooled to 0 °C. A solution of CH3Li (1.4 M in diethyl ether, 0.4
mL, 0.57 mmol) was added to the solution, and the reaction
mixture was stirred for 15 min at 0 °C. 4-Methoxyphenyl
isocyanate (0.23 mL, 1.59 mmol) was added dropwise to the
mixture, and the reaction mixture was stirred for 30 min at 0
°C. The reaction was quenched with water, and the mixture
was extracted with ethyl acetate. The organic phase was
washed with brine, dried (Na2SO4), and concentrated. The
residue was purified by flash column chromatography using
deactivated silica gel and 10% ethyl acetate in hexanes
(containing 2% NEt3) as eluent to afford 1-(anisylcarbamoyl-
oxy)-1-(2-nitrophenyl)-2,4-hexadiene (298 mg, 71%) as a brown
oil. IR (neat): 3325 (N-H), 3020, 2916, 2834, 1730 (CdO),
1601, 1522, 1211, 1029 cm-1. 1H NMR (CDCl3): δ 7.93 (1H, d,
J ) 9.0 Hz), 7.61 (2H, m), 7.42 (1H, m), 7.24 (2H, d, J ) 7.5
Hz), 6.82 (3H, m), 6.66 (1H, bs), 6.31 (1H, dd, J ) 15.0, 10.5
Hz), 6.02 (1H, m), 5.78 (1H, dd, J ) 6.9, 3.3 Hz), 5.73 (1H, dd,
J ) 6.9, 3.6 Hz), 3.76 (3H, s), 1.74 (3H, d, J ) 6.6 Hz). 13C
NMR (CDCl3): δ 155.8, 152.2, 147.6, 135.3, 133.9, 133.2, 132.1,
130.4, 130.1, 128.3, 128.0, 126.2, 124.4 (two carbons), 120.4,
114.0 (two carbons), 72.0, 55.4, 18.2. HRMS (FAB, [M - CO2]+):
calcd for C19H20N2O3: 324.1473, found 324.1474.
1
was used directly in the next step. H NMR (CDCl3): δ 7.56
(1H, s), 6.72 (1H, s), 6.20 (2H, s), 5.75 (1H, m), 5.50 (1H, m),
4.69 (1H, m), 2.90 (2H, m), 2.79 (1H, bs), 1.70 (3H, d, J ) 6
Hz).
1-(3,4-Meth ylen ed ioxy-6-n itr op h en yl)-2,4-h exa d ien -1-
on e. 1-(3,4-Methylenedioxy-6-nitrophenyl)-3-hydroxy-4-hexen-
1-one (6.967 g, 21.5 mmol) was dissolved in dry CH2Cl2 (109
mL), and the solution was cooled to -78 °C. Triethylamine
(6.0 mL, 43 mmol) was added quickly, and the reaction was
stirred for 10 min. Methanesulfonyl chloride (3.33 mL, 43
mmol) was added dropwise, and the resulting solution was
stirred at -78 °C for 30 min. The reaction was diluted with
water, and the phases were separated. The aqueous phase was
extracted with CH2Cl2. The combined CH2Cl2 extract was
washed with 1 M HCl and saturated aqueous NaHCO3 and
dried (MgSO4). The residue was purified by flash chromatog-
raphy using 17% ethyl acetate in hexanes to afford mostly pure
1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-hexadiene-1-one, which
was obtained analytically pure by recrystallization from di-
isopropyl ether (3.14 g, 56%). Mp: 90-91 °C. IR (CH2Cl2):
3113, 3063, 3024, 2968, 2914, 2852, 1660 (CdO), 1630, 1610,
1589, 1520, 1483, 1425, 1395, 1345, 1157, 1036, 995, 931, 875
1
cm-1. H NMR (CDCl3): δ 7.60 (1H, s), 6.76 (1H, s), 6.80 (1H,
m), 6.08-6.30 (5H, m), 1.85 (3H, d, J ) 6.3 Hz). 13C NMR
(CDCl3): δ 192.5, 152.3, 148.7, 146.1, 141.8, 139.6, 133.0, 130.0,
127.4, 107.4, 104.8, 103.5, 18.8. Anal. Calcd for C13H11NO5:
C, 59.77; H, 4.24; N, 5.36. Found: C, 59.85; H, 4.31; N, 5.29.
1-(3,4-Meth ylen ed ioxy-6-n itr op h en yl)-2,4-h exa d ien -1-
o1 (12). 1-(3,4-Methylenedioxy-6-nitrophenyl)-2,4-hexadiene-
1-one (3.66 g, 14.0 mmol) was dissolved in a mixture of THF
(40 mL) and CH3OH (73 mL), and the solution was cooled to
0 °C. Sodium borohydride (700 mg, 19 mmol) was added in
small portions, and this turbid mixture was stirred at 0 °C
for 30 min. The reaction mixture was diluted with water, and
the mixture was extracted with ethyl acetate. The combined
ethyl acetate was dried (MgSO4) and evaporated to give fairly
clean 1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-hexadiene-1-o1
(3.90 g) as an orange, tacky oil. The oil was further purified
by crystallization from ether/hexanes to afford light yellow
crystals. Mp: 85-86 °C. IR (KBr): 3538, 3413, 3089, 3069,
3019, 2962, 2914, 2852, 1657, 1617, 1515, 1482, 1332, 1258,
3,4-Meth ylen ed ioxy-6-n itr oa cetop h en on e. 3,4-Methyl-
enedioxyacetophenone (10 g, 61 mmol) was dissolved in CH3-
NO2 (78 mL) at room temperature; 90% HNO3 (12.0 mL, 270
mmol) was added slowly with stirring and cooling with a 23
°C water bath. Stirring was continued for 3 h, at which time
the reaction appeared complete, as evidenced by TLC analysis.
The reaction mixture was carefully neutralized by the addition
of saturated aqueous NaHCO3 solution and extracted with
CH2Cl2. The CH2Cl2 solution was dried (MgSO4), and the
residue was purified by flash chromatography using 33% ethyl
1
1035, 991, 931, 878, 601 cm-1. H NMR (CDCl3): δ 7.48 (1H,
s), 7.21 (1H, s), 6.35 (1H, dd, J ) 13, 8 Hz), 6.15 (2H, bs), 6.05
(1H, m), 5.79 (3H, m), 2.42 (1H, d, J ) 3 Hz), 1.75 (3H, d, J )
6 Hz). 13C NMR (CDCl3): δ 152.2, 147.0, 141.7, 136.0, 131.7,
(20) Fetter, J .; Lempert, K.; Møller, J . Tetrahedron 1975, 31, 2559-
2569.

PeNB and PeNP Photochemically Removable Protecting Groups
J . Org. Chem., Vol. 64, No. 14, 1999 5047
131.3, 130.4, 129.8, 107.3, 105.2, 102.9, 69.3, 18.1. Anal. Calcd
for C13H13NO5: C, 59.31; H, 4.98; N, 5.32. Found: C, 59.23;
H, 5.08; N, 5.40. UV: λmax 350 nm, ꢀ ) 5659 (CH3CN). HRMS
(FAB, [M - H]+): calcd for C13H12NO5 262.0715, found
262.0721.
(1H, s), 6.27 (1H, dd, J ) 15.2, 10.8 Hz), 6.10 (2H, m), 6.00
(1H, m), 5.73 (1H, dd, J ) 14.8, 6.8 Hz), 5.59 (1H, dd, J )
15.2, 6.4 Hz), 5.48 (1H, d, J ) 6.8 Hz), 4.43 (1H, m), 3.30 (1H,
m), 1.73 (3H, d, J ) 6.8 Hz), 1.58 (2H, m), 1.28 (6H, m), 0.88
(3H, t, J ) 6.4 Hz). 13C NMR (CDCl3): δ 152.1, 146.8, 142.0,
135.2, 131.9, 130.6, 129.1, 106.9 (2 carbons), 104.9, 102.7, 76.5,
69.0, 31.5, 29.6, 25.7, 22.5, 18.0, 13.9. HRMS (FAB, [M - H]+):
calcd for C19H24NO5 346.1654, found 346.1640 (this compound
contains an inseparable minor olefin stereoisomer (<15%)).
1-P h en oxy-1-(3,4-m eth ylen ed ioxy-6-n itr op h en yl)-2,4-
h exa d ien e (16). Tributylphosphine (0.35 mL, 1.42 mmol) was
added to a solution of 1-(3,4-methylenedioxy-6-nitrophenyl)-
2,4-hexadien-1-ol (249 mg, 0.946 mmol) and phenol (134 mg,
1.42 mmol) in dry benzene (10 mL) at 0 °C. 1,1′-(Azodicarbo-
nyl)dipiperidine (360 mg, 1.42 mmol) was added to the solution
with stirring. After 10 min, the reaction mixture was allowed
to warm to room temperature and stirred for 20 h. Hexane
was added, and the mixture was filtered through Celite. The
solvent was evaporated, and the residue was purified by flash
column chromatography using deactivated silica gel and 5%
ethyl acetate in hexanes (containing 2% NEt3) as eluent to
afford 1-phenoxy-1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-
hexadiene (211 mg, 66%) as a yellow oil. IR (neat): 3026, 2915,
1-(Ben zoyloxy)-1-(3,4-m eth ylen ed ioxy-6-n itr op h en yl)-
2,4-h exa d ien e (13). A mixture of 1-(3,4-methylenedioxy-6-
nitrophenyl)-2,4-hexadien-1-ol (500 mg, 1.90 mmol) and 4-(di-
methylamino)pyridine (23 mg, 0.19 mmol) was dissolved in dry
CH2Cl2 (10 mL), and pyridine (0.46 mL, 5.70 mmol) was added
to this solution in one portion. The solution was cooled to 0
°C, and benzoyl chloride (0.33 mL, 2.85 mmol) was added
dropwise. The reaction was stirred for 20 min at 0 °C and then
allowed to warm to room temperature while stirring overnight.
The reaction mixture was diluted with water and extracted
with CH2Cl2. The organic phase was washed with saturated
aqueous CuSO4 solution and brine, dried (Na2SO4), and
concentrated. The residue was purified by flash column
chromatography using deactivated silica gel and 5% ethyl
acetate in hexanes (containing 2% NEt3) as eluent to afford
pure 1-(benzoyloxy)-1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-
hexadiene (671 mg, 96%) as a yellow oil. IR (neat): 3056, 3008,
2912, 1720 (CdO), 1520, 1320, 1104, 1040 cm-1 1H NMR
.
1612, 1596, 1518, 1504, 1485, 1330, 1258, 1231, 1036 cm-1
.
(CDCl3): δ 8.07 (2H, dd, J ) 8.6, 1.1 Hz), 7.60-7.40 (4H, m),
7.11 (2H, m), 6.38 (1H, dd, J ) 15.3, 10.3 Hz), 6.06 (3H, m),
5.84 (1H, dd, J ) 8.7, 6.1 Hz), 5.80 (1H, dd, J ) 14.9, 8.1 Hz),
1.75 (3H, d, J ) 6.4 Hz). 13C NMR (CDCl3): δ 165.0, 152.2,
147.3, 141.9, 133.6, 133.3, 132.6, 132.3, 130.2, 129.64, 129.58,
128.4, 126.1, 106.6, 105.32, 105.29, 103.0, 77.0, 71.6, 18.2.
HRMS (FAB, M+): calcd for C20H17NO6 367.1056, found
367.1056.
1H NMR (CDCl3): δ 7.44 (1H, s), 7.26 (2H, m), 7.15 (1H, dd, J
) 15.9, 1.2 Hz), 6.95 (4H, m), 6.10 (1H, dd, J ) 15.6, 6.3 Hz),
6.06 (2H, s), 5.85 (1H, ddd, J ) 15.6, 6.3, 1.2 Hz), 5.64 (1H,
m), 5.26 (1H, td, J ) 6.3, 0.6 Hz), 1.76 (3H, ddd, J ) 6.3, 1.5,
0.6 Hz). 13C NMR (CDCl3): δ 157.4, 151.6, 147.2, 141.6, 132.8,
129.4, 129.2 (two carbons), 129.0, 127.7, 120.9, 116.1 (two
carbons), 107.2, 105.1, 102.9, 78.7, 74.4, 17.9. HRMS (FAB,
[M - H]+): calcd for C19H16NO5 338.1028, found 338.1024 (this
compound contains an inseparable minor olefin stereoisomer
(<13%)).
1-(Ben zyloxy)-1-(3,4-m et h ylen ed ioxy-6-n it r op h en yl)-
2,4-h exa d ien e (14). NaH (137 mg, 5.70 mmol) was added to
a solution of 1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-hexa-
dien-1-ol (500 mg, 1.90 mmol) in dry DMF (10 mL) at 0 °C.
Benzyl bromide (0.29 mL, 2.47 mmol) was added dropwise to
the mixture, and the reaction mixture was stirred for 5 h at
room temperature. The reaction was quenched with water and
extracted with diethyl ether. The organic phase was washed
with water and brine, dried (Na2SO4), and concentrated. The
residue was purified by flash column chromatography using
deactivated silica gel and 5% ethyl acetate in hexanes (con-
taining 2% NEt3) as eluent to afford pure 1-(benzyloxy)-1-(3,4-
methylenedioxy-6-nitrophenyl)-2,4-hexadiene (369 mg, 55%)
as an orange oil. IR (neat): 3008, 2928, 2864, 1680, 1632, 1520,
1480, 1344, 1056 cm-1. 1H NMR (CDCl3): δ 7.32 (7H, m), 6.34
(1H, m), 6.10 (2H, dd, J ) 3.6, 1.1 Hz), 6.02 (1H, m), 5.75 (1H,
dd, J ) 15.0, 6.7 Hz), 5.63 (2H, dd, 6.1, 3.0 Hz), 4.50 (1H, d, J
) 11.5 Hz), 4.43 (1H, d, J ) 11.5 Hz), 1.75 (3H, d, J ) 6.4 Hz).
13C NMR (CDCl3): δ 152.2, 146.9, 142.1, 137.7, 134.7, 132.5,
131.1, 130.5, 128.6, 128.3, 127.63, 127.58, 107.0, 105.0, 102.8
(two carbons), 77.0, 76.1, 70.7, 18.1. HRMS (FAB, [M - H]+):
calcd for C20H18NO5 352.1185, found 352.1184. Anal. Calcd for
Rep r esen ta tive P h otod ep r otection of a P eNB Der iva -
tive (8). A 10 mM solution of 1-(2-phenylacetoxy)-1-(2-nitro-
phenyl)-2,4-hexadiene (56 mg, 0.166 mmol) in CH3OH (16.6
mL) was prepared in an oven-dried quartz flask, and the flask
was tightly capped under an argon atmosphere. The solution
was irradiated for 90 min with vigorous stirring using a
Rayonet photochemical reactor with 254 nm bulbs. The solvent
was evaporated, and the residue was dissolved in CH2Cl2 (3
mL). The solution was extracted with aqueous 1 N NaOH
solution. The aqueous phase was washed with diethyl ether
and acidified with concentrated HCl solution. The resulting
aqueous solution was extracted with diethyl ether. The
combined organic layers were dried (Na2SO4) and concentrated
to give 17.0 mg of phenylacetic acid (75%).
Rep r esen ta tive P h otod ep r otection of a P eNP Der iva -
tive (14). A 10.1 mM solution of 1-(benzyloxy)-1-(3,4-methyl-
enedioxy-6-nitrophenyl)-2,4-hexadiene (50 mg, 0.141 mmol) in
CH3OH (14 mL) was prepared in an oven-dried Pyrex flask,
and the flask was tightly capped under argon atmosphere. The
solution was irradiated for 3 h with vigorous stirring using a
Rayonet photochemical reactor with 350 nm bulbs. The solvent
was evaporated, and the residue was purified by flash column
chromatography using 20% ethyl acetate in hexanes as eluent
to afford 11.6 mg of benzyl alcohol (76%).
C
20H19NO5: C, 67.98; H, 5.42; N, 3.96. Found: C, 67.91; H,
5.41; N, 3.90.
1-(H exyloxy)-1-(3,4-m et h ylen ed ioxy-6-n it r op h en yl)-
2,4-h exa d ien e (15). 1-(3,4-Methylenedioxy-6-nitrophenyl)-2,4-
hexadien-1-ol (500 mg, 1.90 mmol) was dissolved in dry CH3CN
(10 mL) at room temperature, and hexyl iodide (0.42 mL, 2.85
mmol) and KF/alumina reagent (40 %, 690 mg, 4.75 mmol)
were added in one portion. The reaction mixture was stirred
vigorously for 10 h at room temperature. More hexyl iodide
(0.42 mL, 2.85 mmol) and KF/alumina reagent (40%, 690 mg,
4.75 mmol) were added, and the reaction was stirred overnight.
More KF/alumina reagent (40%, 690 mg, 4.75 mmol) was
added, and the reaction was stirred for another 10 h. The
mixture was filtered through Celite, and the filter cake was
washed with ethyl acetate (50 mL). The solvents were evapo-
rated, and the residue was purified by flash column chroma-
tography using deactivated silica gel and 5% ethyl acetate in
hexanes (containing 2% NEt3) as eluent to afford pure 1-(hexyl-
oxy)-1-(3,4-methylenedioxy-6-nitrophenyl)-2,4-hexadiene (434
mg, 66%) as an orange oil. IR (neat): 2954, 2930, 2859, 1519,
Ack n ow led gm en t. Financial support by NIH GM-
46720 and a postdoctoral fellowship from the Korea
Science and Engineering Foundation KOSEF (Y.R.L.)
are acknowledged. J eff Bednarski (NIGMS Summer
Scholar, 1993) performed key preliminary studies that
made this work possible.
Su p p or tin g In for m a tion Ava ila ble: Procedure for GC
response factor analyses and1H NMR and 13C NMR spectra
of compounds characterized by HRMS (3a ,b, 6, 8-11, 13, 15,
and 16) as evidence of their purity. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
1484, 1254, 1037 cm-1. H NMR (CDCl3): δ 7.44 (1H, s), 7.16
J O982383D