α-Carboxy-6-nitroveratryl: A photolabile protecting group for carboxylic acids

Article abstract of DOI:10.1021/jo100783v

(Figure presented) The synthesis of a new photolabile protecting group for carboxylic acids, α-carboxy-6-nitroveratryl (αCNV), is described. Bromide 3, prepared in four steps from 3,4-dimethoxyphenylacetic acid, was used to alkylate carboxylic acids under mild conditions in good yield. Palladium-catalyzed deallylation afforded the acids 4a-h, which underwent rapid and quantitative photolysis at wavelengths longer than 300 nm to liberate the carboxylic acid in good to quantitative yield. The rate of photolysis and quantum yield were determined to be 325 s^-1 and 0.17.

Full text of DOI:10.1021/jo100783v

pubs.acs.org/joc
molecule can occur on the millisecond to microsecond time
scale, beyond the limit of flow techniques.
r-Carboxy-6-nitroveratryl: A Photolabile Protecting
Group for Carboxylic Acids
Photolabile protecting groups have been developed for a
number of biologically relevant functional groups, including
carboxylates,2 phosphates,3 alcohols,2c,4 phenols,2c,g,5 thiols,4b
amines,6 and carbonyls.7 To be useful in biological experi-
ments, the protecting group should display rapid photolysis
kinetics, high aqueous solubility and dark stability, good
biocompatibility (including the photolysis products), high
quantum yield, and long-wavelength excitation.3
In particular, the low wavelength, high energy light re-
quired for deprotection of certain protecting groups may
result in cell damage or protein modification, and accord-
ingly, there has been interest in protecting groups that will
release acids upon irradiation at longer wavelengths.2b,8
Given the broad applicability of photolabile caging, it is
desirable to have at our disposal a number of photolabile
protecting groups offering a range of photolysis character-
istics.
Alexander G. Russell,† Maria-Eleni Ragoussi,†
Rui Ramalho,† Christopher W. Wharton,‡ David Carteau,§
Dario M. Bassani,*,§ and John S. Snaith*,†
†School of Chemistry, and ‡School of Biosciences, University
of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K., and
§ISM CNRS UMR 5255, Universiteꢀ Bordeaux 1, 33405
Talence, France
d.bassani@ism.u-bordeaux1.fr; j.s.snaith@bham.ac.uk
Received April 26, 2010
The 2-nitrobenzyl group and its derivatives are the most
widely studied photolabile protecting groups. The 2-nitro-
benzyl group, discovered by Barltrop and Schofield in 1966,
shows millisecond kinetics for acid release at relatively low
wavelength excitation.9 The R-carboxy-2-nitrobenzyl (RCNB)
protecting group shows much faster photolysis kinetics, re-
leasing acids on the microsecond time scale, but still has a low
excitation wavelength.10 By contrast, the 6-nitroveratryl pro-
tecting group may be removed by photolysis at longer wave-
lengths up to420 nm, but the time scalefor acid release is of the
order of seconds.11
Herein, we present the results of our studies into a new
photolabile protecting group, the R-carboxy-6-nitroveratryl
(RCNV) group. Our aim was to produce a photolabile
protecting group with long wavelength absorption and im-
proved kinetics for acid release compared with the 6-nitro-
veratryl group.
The synthesis of a new photolabile protecting group for
carboxylic acids, R-carboxy-6-nitroveratryl (RCNV), is
described. Bromide 3, prepared in four steps from 3,4-
dimethoxyphenylacetic acid, was used to alkylate carbox-
ylic acids under mild conditions in good yield. Palladium-
catalyzed deallylation afforded the acids 4a-h, which
underwent rapid and quantitative photolysis at wave-
lengths longer than 300 nm to liberate the carboxylic acid
in good to quantitative yield. The rate of photolysis and
quantum yield were determined to be 325 s-1 and 0.17.
(3) Pelliccioli, A. P.; Wirz, J. Photochem. Photobiol. Sci. 2002, 1, 441–458.
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Published on Web 06/10/2010
DOI: 10.1021/jo100783v
r
2010 American Chemical Society

Russell et al.
JOCNote
SCHEME 1. Formation of Esters 4a-h
TABLE 1. Preparation and Photolysis of Esters 4a-h
esterification deallylation photolysis
yieldc (%)
entry ester
acid
(%)
(%)
1
2
3
4
5
6
7
8
4a acetica
68a
71
90
73
84a
82
76
78
79
80
75
71
90
4b propanoic
4c hexanoic
4d benzoic
quant
quant
quant
72
92
quant
quant
4e Penicillin Ga
80
4f
Gly
60b
64b
54b
4g GABA
4h Phe
aEsterification employed the sodium salt rather than the free acid and
K2CO3. bOverall yield for deallylation and Boc cleavage. cPhotolysis was
performed in deuterated water, methanol, or acetone. Photolysis yield
was measured by integration of resonances in the 1H NMR spectrum in
comparison to an internal standard (DMSO or Me6Si2); conversion was
quantitative in all cases.
The RCNV protecting group was synthesized from the
commercially available 3,4-dimethoxyphenylacetic acid 1,
which was nitrated and esterified with allyl alcohol to give 2
in an overall yield of 80%. The allyl ester was chosen for its
ability to be removed under essentially neutral conditions,
compatible with acid-sensitive substrates such as β-lactams
(vide infra).12 Direct reaction between an alkyl halide and a
carboxylate salt provides a very mild and clean method for
ester formation, and so 2 was transformed into bromide 3 by
a two-step procedure. Diazo transfer using methansulfonyl
azide and DBU smoothly afforded the diazo ester, which was
quantitatively converted into the bromide 3 by treatment
with HBr/AcOH, Scheme 1.
FIGURE 1. Transient absorption spectrum of 4d in ethanol/water
(1:1) 10 μs after pulsed excitation at 355 nm and decay of the
transient absorption monitored at 390 nm. The red line represents
the best fit according to a monoexponential decay with k = 325 s-1
.
The feature at 14 ms is an experimental artifact.
diazo compounds which are known by products from the
photolysis of some nitrobenzyl derivatives.13
The bromide 3 was reacted with a range of acids in DMF
with potassium carbonate as base, affording the correspond-
ing esters in good to excellent yields. Allyl ester cleavage was
accomplished by stirring with Pd(PPh3)4 and tributylammo-
nium formate in THF, affording the deprotected esters
4a-h, Table 1. The allyl cleavage was normally complete
within 15 min; excessively long reaction times (several hours)
led to decarboxylation, affording the corresponding 6-nitro-
veratryl derivatives 5. In the case of the amino acid deriva-
tives 4f-h, TFA treatment effected Boc group removal,
yielding the amino acid esters as the TFA salts; the ester
showed no signs of instability toward TFA.
The photolability of the compounds was determined by
irradiation with a 400 W medium-pressure mercury lamp,
filtered through Pyrex to cut off wavelengths below 300 nm.
Photolyses were carried out on solutions prepared either in
deuterated water, methanol or acetone; released product and
remaining starting material was determined by integration of
the relevant resonances in the 1H NMR spectrum in compar-
ison to an internal standard (for a typical spectrum see
Supporting Information, Figure S4). Conversion of the
starting material was quantitative, while control solutions
kept in the dark showed no evidence of degradation even
after several days. Darkening of the solution occurred as the
photolysis proceeded, possibly as a result of the formation of
The quantum yield of the photorelease reaction in ethanol/
water (1:1) solutions was determined by ferrioxalate actino-
metry to be 0.17 ( 0.03 upon irradiation at 365 nm. Laser
flash photolysis (λex = 355 nm) of solutions of 4d in ethanol/
water (1:1) revealed the rapid formation of a transient
absorption with a maximum at 410 nm (Figure 1). The latter
is assigned to the aci-nitro intermediate based on its similar-
ity with previously reported absorption spectra of ana-
logous intermediates. Thephotolysis kinetics weredetermined
by monitoring the transient absorption at 390 nm, which
decayed monoexponentially on the millisecond time scale
(k = 325 s-1) toward the initial absorbance level. The decay
of the aci-nitro signal has previously been correlated with
product release, although detailed investigations by Wirz and
co-workers14 and by Corrie and co-workers15 showed that the
hydrolysisof the hemiacetal canbe rate-limiting, withthe rate-
limiting step being dependent on solvent, pH, and the nature
of the leaving group.
To provide a simple comparison between the RCNB and
RCNV protecting groups, the acetates of both were photo-
lyzed side-by-side in deuterated acetone with a 400 W Pyrex-
jacketed, medium-pressure mercury lamp. As evident from
Figure 2, under these conditions release of acetic acid from
(13) Ried, W.; Wilk, M. Liebigs Ann. Chem. 1954, 590, 91–110.
€
(14) Il’ichev, Y. V.; Schworer, M. A.; Wirz, J. J. Am. Chem. Soc. 2004,
126, 4581–4595.
(15) Corrie, J. E. T.; Barth, A.; Munasinghe, V. R. N.; Trentham, D. R.;
Hutter, M. C. J. Am. Chem. Soc. 2003, 125, 8546–8554.
ꢀ
(12) Kocienski, P. J. In Protecting Groups; Enders, D., Noyori, R., Trost,
B. M., Eds.; Georg Thieme Verlag: Stuttgart, 1994.
J. Org. Chem. Vol. 75, No. 13, 2010 4649

Russell et al.
JOCNote
(from EtOAc); IR (film) 3417 (br), 2942, 1743, 1618, 1584, 1526
cm-1; UV (MeOH) λmax (log ε) 338 (3.89), 243 (4.28), 222 (4.23),
204 (4.35); 1H NMR (300 MHz, acetone-d6) δ 2.17 (s, 3H), 3.97 (s,
6H), 6.88 (s, 1H), 7.19 (s, 1H), 7.70 (s, 1H); 13C NMR (75 MHz,
acetone-d6) δ 20.5, 56.7, 56.8, 70.3, 109.2, 111.6, 124.8, 141.8, 150.2,
154.4, 169.0, 170.0; MS (electrospray) m/z 344 (35, [M - H þ
2Na]þ), 322 (100, [M þ Na]þ); HRMS (electrospray) calcd for
C12H13NO8Na 322.0539, found 322.0543.
Propanoic Acid r-Carboxy-4,5-dimethoxy-2-nitrobenzyl
Ester (4b). Propanoic acid R-allyloxycarbonyl-4,5-dimethoxy-
2-nitrobenzyl ester (445 mg, 1.26 mmol) was treated with Pd-
(PPh3)4 (50 mg, 0.043 mmol), PPh3 (330 mg, 1.26 mmol), and
Bu3NHCO2H (1.2 M solution in THF, 4.2 mL, 5.04 mmol)
according to the general procedure to give propanoic acid
R-carboxy-4,5-dimethoxy-2-nitrobenzyl ester (4b) (316 mg,
80%) as a colorless oil: IR (film) 3520 (br), 3310 (br), 2942,
1742, 1618, 1584, 1525 cm-1; UV (MeOH) λmax (log ε) 338
(4.01), 243 (4.38), 206 (4.41); 1H NMR (300 MHz, acetone-d6) δ
1.14 (t, J = 7.5 Hz, 3H), 2.50 (q, J = 7.5 Hz, 2H), 3.95 (s, 3H),
3.96 (s, 3H), 6.90 (s, 1H), 7.19 (s, 1H), 7.69 (s, 1H); 13C NMR (75
MHz, acetone-d6) δ 10.2, 28.6, 57.6, 57.7, 71.2, 110.1, 112.5,
125.9, 142.7, 151.1, 155.3, 170.1, 174.4; MS (electrospray) m/z
336 (22, [M þ Na]þ), 240 (100); HRMS (electrospray) calcd for
C13H15NO8Na 336.0695, found 336.0685.
FIGURE 2. Comparative photolysis of RCNB acetate and 4a in
acetone through Pyrex.
the RCNV ester is significantly faster than from the RCNB
ester.
In conclusion, we have developed a short, high-yielding
route to RCNV esters, applicable to a range of carboxylic
acid derivatives. The RCNV protecting group has the desir-
able absorption characteristics of the 6-nitroveratryl group,
but RCNV esters photolyze some 2-3 orders of magnitude
faster than 6-nitroveratryl esters. The chemistry is applicable
to the protection and release of neurotransmitters (e.g.,
glycine and GABA) and β-lactam antibiotics (e.g., penicillin),
as well as simple carboxylic acids and should be readily
extendable to the caging of peptides and other biomolecules.
Hexanoic Acid r-Carboxy-4,5-dimethoxy-2-nitrobenzyl Ester
(4c). Hexanoic acid R-allyloxycarbonyl-4,5-dimethoxy-2-nitro-
benzyl ester (267 mg, 0.68 mmol) was treated with Pd(PPh3)4 (30
mg, 0.026 mmol), PPh3 (177 mg, 0.68 mmol), and Bu3NHCO2H
(1.2 M solution in THF, 2.27 mL, 2.72 mmol) according to
the general procedure to give hexanoic acid R-carboxy-4,5-
dimethoxy-2-nitrobenzyl ester (4c) (180 mg, 75%) as a colorless
oil: IR (film) 3530 (br), 2932, 2858, 1745, 1616, 1584, 1526 cm-1
;
Experimental Section
UV (MeOH) λmax (log ε) 337 (4.08), 241 (4.46), 221 (4.46),
208 (4.47); 1H NMR (300 MHz, CDCl3) δ 0.83-0.88 (m, 2H),
1.24-1.31 (m, 4H), 1.60-1.67 (m, 2H), 2.37-2.46 (m, 2H), 3.95
(s, 3H), 3.97 (s, 3H), 6.92 (s, 1H), 7.02 (s, 1H), 7.66 (s, 1H),
10.32 (br s, 1H); 13C NMR (75 MHz, CDCl3) δ 22.2, 24.4,
31.1, 33.8, 56.4, 56.5, 69.6, 108.3, 110.9, 123.6, 140.5, 149.1,
153.2, 172.3; MS (electrospray) m/z 378 (100, [M þ Na]þ);
HRMS (electrospray) calcd for C16H21NO8Na 378.1165, found
378.1159.
General Esterification Procedure. The acid (2.08 mmol, 1.5
equiv) was dissolved in DMF (20 mL), and K2CO3 (2.08 mmol,
1.5 equiv) was added. The suspension was stirred for 30 min at
room temperature before a solution of bromide 3 (1.39 mmol,
1 equiv) in DMF (5 mL) was added. Alternatively, if the
carboxylate salt of the acid was available, this (2.08 mmol,
1.5 equiv) was suspended in DMF and a solution of the bromide
(1.39 mmol, 1.0 equiv) added. The solution was stirred at room
temperature until no bromide remained (1 h to overnight). The
reaction mixture was poured into water and extracted with
Et2O. The combined organic extracts were washed with 50%
saturated NaHCO3 and water, dried over MgSO4, and concen-
trated. The esters did not usually contain significant impurities,
but column chromatography (100% hexane to 7:3 hexane/
EtOAc) was necessary to remove residual DMF.
Deallylation Procedure. Pd(PPh3)4 and PPh3 were dissolved in
degassed THF (5 mL) and stirred at rt for 5 min in the dark. A
1.2 M solution of Bu3NHCOOH (made by mixing a 1:1 molar
ratio of Bu3N and HCOOH in dry, degassed THF) was added
followed by a solution of the ester in THF (5 mL). When all of
the ester had been consumed (TLC), the THF was evaporated
and the residue was partitioned between 50% saturated aqueous
NaHCO3 and Et2O. The organic layer was extracted with 50%
saturated NaHCO3, and the combined aqueous layers were
washed with Et2O. The aqueous phase was acidified to pH
1-2 with 2 M HCl and extracted with EtOAc. The combined
EtOAc layers were dried over MgSO4 and concentrated to give
the acid.
Benzoic Acid r-Carboxy-4,5-dimethoxy-2-nitrobenzyl Ester
(4d). Benzoic acid R-allyloxycarbonyl-4,5-dimethoxy-2-nitro-
benzyl ester (408 mg, 1.02 mmol) was treated with Pd(PPh3)4
(40 mg, 0.035 mmol), PPh3 (270 mg, 1.03 mmol), and Bu3NH-
CO2H (1.2 M solution in THF, 3.4 mL, 4.08 mmol) according to
the general procedure to give benzoic acid R-carboxy-4,5-
dimethoxy-2-nitrobenzyl ester (4d) (261 mg, 71%) as a colorless
solid: mp 53-56 °C; IR (film) 3520 (br), 3280 (br), 2940, 1727,
1584, 1526 cm-1; UV (MeOH) λmax (log ε) 324 (3.75), 283 (3.77),
1
230 (4.38), 206 (4.31); H NMR (300 MHz, CDCl3) δ 3.95 (s,
3H), 3.96 (s, 3H), 7.12 (broad s, 2H), 7.44 (t, J = 7.4 Hz, 2H),
7.58 (t, J = 7.4 Hz, 1H), 7.69 (s, 1H), 8.06 (d, J = 7.4 Hz, 2H),
9.69 (broad s, 1H); 13C NMR (75 MHz, CDCl3) δ 56.6, 56.7,
70.6, 108.6, 111.5, 123.7, 128.7, 128.8, 130.1, 133.9, 140.6, 149.4,
153.5, 165.2, 172.7; MS (electrospray) m/z 400 (10, [M þ K]þ),
384 (100, [M þ Na]þ); HRMS (electrospray) calcd for
C17H15NO8Na 384.0695, found 384.0706.
Penicillin G r-Carboxy-4,5-dimethoxy-2-nitrobenzyl Ester
(4e). Penicillin G R-allyloxycarbonyl-4,5-dimethoxy-2-nitro-
benzyl ester (112 mg, 0.18 mmol) was treated with Pd(PPh3)4
(9 mg, 0.008 mmol), PPh3 (48 mg, 0.18 mmol), and Bu3NH-
CO2H (1.2 M solution in THF, 0.61 mL, 0.73 mmol) according
to the general procedure. Following removal of the solvent, the
residue was subjected to purification by HPLC to afford the
tributylammonium salt (tR 34.57 min, 100:0 to 0:100 water/
acetonitrile over 40 min). This was dissolved in water (5 mL),
acidified to pH 3 with HCl, and immediately extracted with ethyl
Acetic Acid r-Carboxy-4,5-dimethoxy-2-nitrobenzyl Ester
(4a). Acetic acid R-allyloxycarbonyl-4,5-dimethoxy-2-nitroben-
zyl ester (428 mg, 1.26 mmol) was treated with Pd(PPh3)4 (50 mg,
0.043 mmol), PPh3 (330 mg, 1.26 mmol), and Bu3NHCO2H (1.2 M
solution in THF, 4.2 mL, 5.04 mmol) according to the general
procedure to give acetic acid R-carboxy-4,5-dimethoxy-2-nitroben-
zyl ester (4a) as a colorless solid (298 mg, 79%): mp 148-151 °C
4650 J. Org. Chem. Vol. 75, No. 13, 2010

Russell et al.
JOCNote
acetate. Drying over MgSO4 and removal of the solvent gave
penicillin G R-carboxy-4,5-dimethoxy-2-nitrobenzyl ester (4e)
(83 mg, 80%) as a colorless gum: IR (film) 3406 (br), 2963, 2874,
1784, 1748, 1667, 1632, 1583, 1524 cm-1; UV (H2O) λmax (log ε)
339 (3.70), 297 (3.65), 244 (4.13), 209 (4.40); 1H NMR
(500 MHz, CDCl3) δ 1.37, 1.42, 1.44, 1.48 (4s, 6H), 3.63 (s,
2H), 3.93, 3.95, 3.96, 3.98 (4s, 6H), 4.39, 4.48 (2s, 1H), 5.47, 5.52
(2d, J = 4.1 Hz, 1H), 5.59-5.65 (m, 1H), 6.15, 6.21 (2d, J = 8.0
Hz, 1H), 6.82, 6.84 (2s, 1H), 6.97, 7.00 (2s, 1H), 7.24-7.36 (m,
5H), 7.65, 7.69 (2s, 1H); 13C NMR (125 MHz, CDCl3) δ 26.4,
31.6, 31.9, 43.2, 56.5, 56.65, 56.71, 58.9, 64.7, 67.9, 68.0, 70.2,
70.3, 71.0, 71.3, 108.4, 108.6, 111.5, 112.0, 127.8, 128.9, 129.0,
129.2, 129.6, 133.5, 140.3, 140.6, 149.4, 153.4, 166.2, 166.3,
169.4, 169.5, 171.1, 171.2, 173.2, 173.4; MS (electrospray)
m/z 596 (100, [M þ Na]þ); HRMS (electrospray) calcd for
C26H27N3O10NaS 596.1315, found 596.1332.
164-167 °C; IR (solid) 3100, 2945, 1714, 1701, 1617, 1578, 1532
cm-1; UV (D2O) λmax (log ε) 354 (3.63), 313 (3.69), 244 (4.07),
1
206 (3.91); H NMR (300 MHz, D2O) δ 1.89-1.98 (m, 2H),
2.50-2.68 (m, 2H), 3.00 (t, J = 7.5 Hz, 2H), 3.80 (s, 3H), 3.87 (s,
3H), 6.63 (s, 1H), 7.04 (s, 1H), 7.54 (s, 1H); 13C NMR (75 MHz,
D2O) δ 22.2, 30.7, 38.8, 56.5, 56.6, 71.6, 109.0, 112.7, 123.6,
140.4, 149.0, 153.3, 171.8, 173.5; MS (electrospray) m/z 365
(100, [M þ Na]þ); HRMS (electrospray) calcd for C14H18N2O8-
Na 365.0961, found 365.0963.
N-(tert-Butoxycarbonyl)phenylalanine r-Carboxy-4,5-dimethoxy-
2-nitrobenzyl Ester Trifluoroacetate Salt (4h). N-(tert-Butoxy-
carbonyl)phenylalanine R-allyloxycarbonyl-4,5-dimethoxy-2-nitro-
benzyl ester (140 mg, 0.26 mmol) was treated with Pd(PPh3)4
(12 mg, 0.01 mmol), PPh3 (67 mg, 0.26 mmol), and Bu3NHCO2H
(1.2 M solution in THF, 0.9 mL, 1.08 mmol) according to the
general procedure to give a colorless solid which was stirred for 1
h in trifluoroacetic acid (1 mL). The trifluoroacetic acid was
removed in vacuo and the residue purified by HPLC to afford
N-(tert-butoxycarbonyl)phenylalanine R-carboxy-4,5-dimethoxy-
2-nitrobenzyl ester trifluoroacetate salt (4h) (73 mg, 54%) as a
colorless gum: tR 20.79 min (100:0 to 0:100 water/acetonitrile over
N-(tert-Butoxycarbonyl)glycine r-Carboxy-4,5-dimethoxy-2-
nitrobenzyl Ester Trifluoroacetate Salt (4f). N-(tert-Butoxy-
carbonyl)glycine R-allyloxycarbonyl-4,5-dimethoxy-2-nitro-
benzyl ester (250 mg, 0.55 mmol) was treated with Pd(PPh3)4
(30 mg, 0.026 mmol), PPh3 (144 mg, 0.55 mmol), and Bu3NH-
CO2H (1.2 M solution in THF, 1.83 mL, 2.2 mmol) according to
the general procedure to give a colorless solid which was stirred
for 1 h in trifluoroacetic acid (1 mL). Removal of the trifluor-
oacetic acid in vacuo and trituration of the residue with diethyl
ether afforded N-(tert-butoxycarbonyl)glycine R-carboxy-4,5-
dimethoxy-2-nitrobenzyl ester trifluoroacetate salt (4f) (142 mg,
60%) as a colorless solid: mp 166-169 °C; IR (solid) 3070 (br),
2969, 2938, 2906, 2844, 1758, 1727, 1686, 1578, 1513 cm-1; UV
40 min); IR (film) 3425 (br), 2942, 1757, 1674, 1585, 1526 cm-1
;
UV (H2O) λmax (log ε) 348 (3.56), 312 (3.51), 247 (3.90); 1H NMR
(500 MHz, CDCl3) δ 3.07-3.34 (m, 2H), 3.79, 3.80, 3.90, 3.94 (4s,
6H), 4.32-4.37 and 4.55-4.60 (2m, 1H), 6.74-6.84 (m, 2H),
6.98-7.05 and 7.08-7.16 (2m, 5H), 7.55 (s, 1H); 13C NMR (125
MHz, CDCl3) δ 35.9, 36.2, 54.5, 54.8, 56.41, 56.47, 56.55, 72.2,
72.7, 108.2, 108.4, 112.2, 116.0 (q, J = 289 Hz), 122.1, 122.2, 127.6,
127.8, 128.7, 129.0, 129.1, 129.2, 133.0, 133.2, 140.4, 140.5, 149.4,
149.5, 153.47, 153.50, 162.1 (q, J = 37 Hz), 168.0, 169.0, 170.1,
170.3; MS (electrospray) m/z 427 (100, [M þ Na]þ), 405 (20, [M þ
H]þ); HRMS (electrospray) calcd for C19H21N2O8 405.1298,
found 405.1305.
1
(D2O) λmax (log ε) 355 (3.78), 223 (4.23), 208 (3.98); H NMR
(300 MHz, D2O þ NaOD) δ 3.03 (s, 2H), 3.78 (s, 3H), 3.82 (s,
3H), 5.36 (s, 1H), 7.08 (s, 1H), 7.54 (s, 1H); 13C NMR (125 MHz,
D2O þ NaOD) δ 46.8, 58.28, 58.34, 74.6, 110.6, 113.7, 134.5,
142.1, 149.4, 155.0, 180.7, 183.8; MS (electrospray) m/z 337
(100, [M þ Na]þ); HRMS (electrospray) calcd for C12H14N2O8-
Na 337.0648, found 337.0639.
4-(tert-Butoxycarbonylamino)butyric Acid r-Carboxy-4,5-di-
methoxy-2-nitrobenzyl Ester Trifluoroacetate Salt (4g). 4-(tert-
Butoxycarbonylamino)butyric acid R-allyloxycarbonyl-4,5-di-
methoxy-2-nitrobenzyl ester (489 mg, 1.01 mmol) was treated
with Pd(PPh3)4 (40 mg, 0.035 mmol), PPh3 (266 mg, 1.01 mmol),
and Bu3NHCO2H (1.2 M solution in THF, 3.4 mL, 4.08 mmol)
according to the general procedure to give a colorless solid
which was stirred for 1 h in trifluoroacetic acid (1 mL). Removal
of the trifluoroacetic acid in vacuo and trituration of the residue
with diethyl ether afforded 4-(tert-butoxycarbonylamino-
)butyric acid R-carboxy-4,5-dimethoxy-2-nitrobenzyl ester tri-
fluoroacetate salt (4g) (294 mg, 64%) as a colorless solid: mp
Acknowledgment. We thank the Biotechnology and Bio-
logical Sciences Research Council (Grant No. BB/C50446X/
1), the Engineering and Physical Sciences Research Council
(studentships to M.R.), and the University of Birmingham
for financial support, and Mr Graham Burns for HPLC
separations.
Supporting Information Available: Experimental proce-
dures for all compounds not detailed in the Experimental
1
Section. H and 13C NMR spectra for all compounds. Details
of photolysis kinetics and quantum yield determinations. This
material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 75, No. 13, 2010 4651