Reductive cleavage of N-substituted aromatic amides as tert-butyl acylcarbamates

Article abstract of DOI:10.1039/b107330n

Synthetic and spectroscopic details relating to a set of heteroaromatic N-benzyl carboxamides and in particular the corresponding tert-butyl acylcarbamates are reported. These compounds were required to study the postulated effect of various heterocycles

Full text of DOI:10.1039/b107330n

View Article Online / Journal Homepage / Table of Contents for this issue
Reductive cleavage of N-substituted aromatic amides as tert-butyl
acylcarbamates†
Ulf Ragnarsson,*a Leif Grehn,a Hernani L. S. Maiab and Luis S. Monteirob
1
a Department of Biochemistry, University of Uppsala, Biomedical Center, PO Box 576,
SE-751 23 Uppsala, Sweden. E-mail: urbki@bmc.uu.se; Fax: ϩ46 18 55 21 39
b Departamento de Quimica, Universidade do Minho, Gualtar, P-4700-320 Braga, Portugal
Received (in Cambridge, UK) 13th August 2001, Accepted 20th November 2001
First published as an Advance Article on the web 5th December 2001
Synthetic and spectroscopic details relating to a set of heteroaromatic N-benzyl carboxamides and in particular the
corresponding tert-butyl acylcarbamates are reported. These compounds were required to study the postulated effect
of various heterocycles (pyridine and pyrazine with and without condensed benzene rings) on the cleavage of acyl–N
bonds by reduction. All compounds were initially characterized by cyclic voltammetry (CV) which indicated various
degrees of facilitated reduction, reflecting a direct influence of the heterocyclic component. Selected acylcarbamates
were studied with respect to acyl–N bond cleavage by mild reducing agents, and selectively deacylated by activated
aluminium and sodium borohydride. Conversion to acylcarbamates followed by reduction might therefore be a mild,
efficient two-step procedure to effect cleavage of amides, allowing isolation of carbamates and with sodium
borohydride also the corresponding alcohols.
cleavage of the latter. A brief report with some key CV data and
Introduction
a summary of results demonstrating, for the first time, C(O)–
A very large number of methods and reagents are currently
N(Boc) bond cleavage by mild reducing agents has recently
available for the synthesis of amides,1 a fact that reflects the
prominence these compounds have reached in different areas.
been published.8
The high stability of the amide bond makes it hard to cleave, if
desired, and requires aggressive chemicals, often not compatible
with other reactive sites simultaneously present. Therefore,
conversion to amides has only been used in a few cases for
the protection of amino functions,2 for which carbamates in
particular are currently preferred, since they can be tuned to
cleave under mildly acidic, basic or other conditions.
Results
As a starting point for the project, a set of aromatic N-benzyl
carboxamides (1), all previously described in the literature,
and the corresponding N-benzyl N-Boc-arylcarboxamides or
N-benzyl tert-butyl acylcarbamates (2), none of which had been
described before, have been prepared and carefully character-
ized (Scheme 1).
Most members of the subset 1 were prepared, as indicated in
this scheme, from the acid chlorides (X = Cl), and then reacted
to form 2 with Boc2O in the presence of 4-dimethylamino-
pyridine (DMAP) in order to introduce N-Boc groups onto
their amide functions9a without additional tertiary amines,
and with only catalytic amounts of DMAP (see typical
procedure).9b The second step was monitored by TLC and was
in some cases remarkably slow, requiring addition of extra
Boc2O to go to completion, but ultimately afforded recrystal-
lized, analytically pure products in yields of 75–91%.
Electrochemical cleavage of protecting groups is occasionally
feasible3 but only seldom practised. Among groups amenable
to deprotection in this way is N-benzoyl, and on cathodic reduc-
tion benzamides provide the corresponding amines with
concomitant formation of benzyl alcohol.4 A drawback with
N-benzoyl is that rather negative potentials are required and
therefore we are searching for more labile alternatives. To study
the effect of structural changes on cathodic cleavage potentials,
cyclic voltammetry (CV) is especially convenient and by using
this technique we obtained evidence for facilitated electro-
chemical cleavage by introduction of a tert-butoxycarbonyl
(Boc) group on the amide nitrogen.5 Parallel work was
conducted on aromatic sulfonamides, which indicated a strong
influence of the aromatic component on their activation poten-
tials and allowed us to develop mild reductive cleavage and
more labile sulfonamide protecting groups.6 This paper details
related synthetic work dealing with carboxamides of the benz-
amide type, in which the phenyl ring has been replaced by
naphthyl, pyridyl, pyrazyl, 2-quinolyl and quinoxalin-2-yl, as
well as the corresponding N-Boc derivatives, together with typ-
ical reductive cleavage experiments. Since the corresponding
heteroaromatic systems are progressively more easily reduced,7
our working hypothesis was that incorporation of such systems
in conjugation with the amide bonds would facilitate reductive
Additional compounds 4 and 5 (Fig. 1) relating to 1f and
Fig. 1
2f with R = phenyl and methoxycarbonylmethyl have also
been synthesized from inexpensive pyrazinecarboxylic acid. For
the preparation of 4 we chose 3 as a starting material.10 This
acylation agent, previously used to make a set of potential
antituberculosis agents, was judged to be more practical than
the corresponding unstable acid chloride. The dicyclohexyl-
† Electronic supplementary information (ESI) available: reductive
cleavage of N-substituted aromatic amides as tert-butyl acylcarb-
amates. See http://www.rsc.org/suppdata/p1/b1/b107330n/
DOI: 10.1039/b107330n
J. Chem. Soc., Perkin Trans. 1, 2002, 97–101
This journal is © The Royal Society of Chemistry 2002
97

View Article Online
Scheme 1
Table 1 Data from cyclic voltammetry experiments
Entry
Cmpd
Comments, R
ϪEP/Va
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1, 2a–g
1h
2h
1i
See Table in ref. 8
1.25
1.01
2.13
1.79
1.29
1.41
1.13
1.25
1.75
1.56
2.07
Ar = 1-Naphthyl Ph instead of Bnb
2i
Ar = 1-Naphthyl Ph instead of Bnc
4a
4b
5a
5b
6a
6b
7
8
9
10
Ph
CH2COOMe
Ph
CH2COOMe
H
Boc
1.75/∼2.3
1.45/1.76
1.79
Fig. 2 Cyclic voltammogram at a vitreous carbon electrode of 0.005
mol dmϪ3 solution of 2g in DMF, with 0.1 mol dmϪ3 Bu4NBF4 as
supporting electrolyte, at a sweep rate of 100 mV sϪ1 (SCE = standard
calomel electrode).
a Versus SCE; cathode, vitreous carbon; solvent, DMF; supporting elec-
trolyte, Bu4NBF4 0.1 mol dmϪ3; substrate concentration, ∼0.005 mol
dmϪ3 b N-Phenyl-1-naphthamide. c N-Boc-N-phenyl-1-naphthamide.
.
2f and 2g were subjected to controlled potential electrolysis
close to their modestly negative CV activation potentials,
Boc-benzylamine could be isolated in 66 and 96% yield,8
demonstrating the significance of the CV data.
A large number of further reductive cleavage experiments
have been carried out with 2 using activated aluminium in
moist diethyl ether.12 This mild, essentially neutral system
carbodiimide-mediated condensation of pyrazinecarboxylic
acid with 4-nitrophenol gave only 35% of 3 with significant
concomitant formation of contaminating N-acylurea. The
above acid was however, smoothly converted to 3 in 73% yield
by bis(4-nitrophenyl) sulfite in dry pyridine.11 Compound 3 was
reacted with 7 to give 8 and 9 (Scheme 2), which was used to
demonstrate selective cleavage.
was recently shown to cleave S–N bonds in related sulfonamides
6c
with activation potentials above Ϫ1.7 to Ϫ1.8 V,
and
compounds 2c–g were also cleaved under these conditions
with formation of Boc–NH–Bn, directly isolated in yields of
89, 74–85, 90, 49 and 95%, respectively.8 On the other hand, the
naphthoyl derivatives 2a, 2b and 2i underwent only partial
cleavage of the acyl–N bonds and competing naphthalene
reduction took place, requiring purification of these reaction
mixtures by chromatography which allowed isolation of Boc–
NH–Bn in 54–80% yield.
To gain additional information about the applicability of this
seldom used reduction method, a few experiments have been
performed in which two substrates were simultaneously
reduced. By quenching these reactions before they had gone to
completion and determining the ratio of the remaining starting
materials, some information about their relative tendency to
undergo reaction with activated aluminium could be obtained.
These experiments were performed with 2c, 2d, 2f and 2g, using
the first compound as a reference, and the data, shown in Table
2, were generated by integration of the appropriate Boc-Me
Scheme 2
All compounds 1, 2, 4–6 and 7–10 were studied by CV,
of which the data for 1a–g and 2a–g were included in our
preliminary communication.8 To summarize these data, the
activation potentials of the pyridinecarboxamide and naphth-
amide derivatives were less negative than those of the corre-
sponding benzamides, and the analogous pyrazine and
quinoline compounds gave peaks at even higher values. As
shown in Table 1 the values for 1h and 2h are Ϫ1.25 and Ϫ1.01
V which means that they are the highest in the two series of
compounds studied so far. For a typical CV curve, see Fig. 2.
tert-Butyl acylcarbamates are known to undergo fast
aminolysis and alkaline hydrolysis with formation of Boc-
amine,9a,c and in model experiments it has also been demon-
strated that benzoylcarbamates can be cleaved selectively in the
presence of benzamides by electrolysis.5b When compounds
1
and/or benzyl-CH2 signals from H NMR spectra of samples
derived by evaporation of the solvent directly from the reduc-
tion experiments. The results indicate that 2d is reduced
relatively slowly, whereas 2c reacts faster, faster also than 2g
with significantly less negative activation potential. With
respect to the low yield in the preparative cleavage of 2f, the
data under entry 3 may be less reliable.
Among other, more conventional reducing agents with
potential application in the cleavage of acylcarbamates, signifi-
cant results have been obtained with NaBH4. This convenient,
extremely mild reagent was introduced by Weygand and
Frauendorfer for the removal of N-trifluoroacetyl and trichloro-
acetyl groups.13 Ganem et al. have developed a useful cleavage
method for phthalimides based on partial reduction with
98
J. Chem. Soc., Perkin Trans. 1, 2002, 97–101

View Article Online
Table 2 Reduction of 2 with activated aluminium under competition conditions
Entry
Compds
Reagent ratioa
Remaining 2x/2cb
Relative rate
Conversion ratioc
1
2
3
4
5
2d, 2c
2d, 2c
2f, 2c
2g, 2c
2g, 2c
1 : 1 : 2
1 : 1 : 6
1 : 1 : 2
1 : 1 : 2
1 : 1 : 6
1.3
>10
0.7
1.2
3.4
2c ≥ 2d
2c > 2d
2f > 2c?
2c ≥ 2g
2c > 2g
0.8
40
0.7
0.2
9.0
1
a Molecular ratio 2x : 2c : activated aluminium. b By integration of the appropriate Boc-Me and/or Bn-CH2 signals of H NMR spectra. c Ratio
between Boc–NHBn and total remaining starting material by integration of these signals.
this agent.14 The first qualitative experiment with NaBH4 in
absolute ethanol at room temperature was undertaken with 2f,
and TLC indicated not only a surprisingly fast but also an
absolutely clean and complete conversion. These preliminary
results could easily be confirmed in a preparative experiment
(see typical experiment in the Experimental) in which pure
Boc-benzylamine was obtained in 97% isolated yield. The
pyridine derivative 2c gave similar results (98%, no experimental
details given). It is also worth mentioning that the benzoyl
derivative 6b with two Boc-groups on nitrogen is also cleaved by
NaBH4.
ing nonacylated carbamates and amides.16d Di-tert-butyl benzo-
ylimidodicarbonate15b (N,N-bis-Boc-benzamide) was first
shown to be an N-benzoylating agent and subsequently
several other acylimidodicarbonates have been used for
N-acylation.15b–e
The structures of two tert-butyl acylcarbamates including
the benzoyl-N-phenyl species have previously been deter-
mined.17 In this molecule the benzoyl C(O)–N distance is
increased by 0.058 Å in comparison with that of benzanilide,
and the corresponding carbamate bond length by over 0.06 Å
compared with typical Boc-amino acids. The shifts to less
negative activation potentials observed on conversion of vari-
ous model benzamides to benzoylcarbamates5 should also be
highlighted at this point. Obviously tert-butoxycarbonylation
profoundly affects the length and strength of the key amide
bond by interaction of the two N–C(O) orbitals, resulting in a
significant change in resonance stabilization of this bond and
leading to its weakening.
The initial step in the reduction of acylcarbamates with
NaBH4 obviously involves a hydride transfer and should there-
fore lead to the formation of an aldehyde (Scheme 3), but since
Scheme 3
As demonstrated with a set of N-benzyl derivatives,8 on
substitution with a more readily reducible aromatic or hetero-
aromatic system than phenyl, the CV activation potentials of
the corresponding amides and acylcarbamates are significantly
shifted in comparison with the benzamides and benzoylcarb-
amates. In this paper various attempts have been made to
characterize the stability of acyl–N bonds in acylcarbamates
with respect to reductive cleavage. As already mentioned, 2f and
2g could be deacylated by controlled potential electrolysis
above Ϫ1.5 V, i.e. at much less negative potential than that
required to cleave benzoyl.
such compounds are easily and selectively converted to alcohols
by this reagent, further reduction is likely to take place. This
was proved in the case of 2a which upon chromatography of the
crude reaction mixture on a silica column (see Supporting
Information†) furnished pure 1-naphthylmethanol in an
isolated yield of 90% in addition to 91% of the theoretical
amount of Boc-benzylamine. However, careful monitoring by
TLC indicated that the reduction of 2a took place more slowly
than for 2c, requiring only a few hours, and particularly
in comparison with 2f. Initially this seemed reasonable but
it should be pointed out that 2g reacts significantly more
slowly than 2f and therefore careful monitoring of this type of
deacylation is strongly recommended.
At this stage we decided to prepare the ethylenediamine
derivative 9 and subject it to cleavage with NaBH4 as described
in the preceding paragraph. Again a very fast cleavage of the
pyrazinecarbonyl group took place giving 10 but more import-
antly the otherwise comparatively labile naphthalene-2-sulfonyl
(2-Ns) function6c was not at all affected (see Supporting
Information†).Compounds 8–10 were all carefully character-
ized and additional CV data are shown in Table 1.
Selective cleavage of all acylcarbamates investigated with
activation potentials above Ϫ1.75
V was accomplished
with activated aluminium in moist diethyl ether with isolated
yields around 90% except for 2f which seemed to give rise to
a side-reaction. Attempts to correlate the rate of cleavage
by aluminium within this group of substances with their CV
activation potentials under competitive conditions were
inconclusive.
Very clean and complete reductive cleavage of 2 in all
compounds tested (a,c,f,g) was accomplished by NaBH4 in
ethanol, allowing quantitative isolation of Boc–NHBn. Since
this reagent attacks aldehyde and ketone carbonyls with form-
ation of the corresponding alcohols essentially selectively, a
simultaneous formation of such was anticipated and also
demonstrated in one case (for 2a, see Supporting Inform-
ation†). The simple conversion of amides to acylcarbamates
and their easy and complete reduction by NaBH4 to alcohols
might also occasionally be of preparative value.
Sulfonamides can be cleaved by reduction with various
metals and metal salts12 but apart from that they are very stable
to reducing agents including those based on hydride transfer.
Previously we have desulfonylated sulfonylcarbamates by either
controlled potential electrolysis or magnesium in anhydrous
methanol.6a,b After it was found that acylcarbamates could be
deacylated with NaBH4, as mentioned above, we prepared 9
and subjected it to reduction with this agent, whereupon a fast
deacylation but no detectable desulfonylation took place. This
indicates that ordinary sulfonylcarbamates are also stable to
hydride transfer.
Discussion
An ideal protecting group should fulfil a number of criteria
with respect to its introduction, stability to various reagents and
final cleavage. Judged in this perspective, N-benzoyl obviously
fails, since it cannot be selectively cleaved under mild con-
ditions. Among derivatives of N-substituted benzamides or
N-substituted amides in general, tert-butyl acylcarbamates are
of particular interest, because they can be more easily cleaved
by hydrolysis,9a methanolysis,9a aminolysis9c and electrolysis.6
Under the conditions used for formation of N-substituted
tert-butyl acylcarbamates, N-unsubstituted amides give rise to
di-tert-butyl acylimidodicarbonates.15a–e Selective mono-Boc
protection was reported to be unsuccessful,16a but tert-butyl
acylcarbamates have been prepared by RuO4-oxidation of
carbamates16a–c and are stable compounds with increased
sensitivity to acid and base in comparison with the correspond-
J. Chem. Soc., Perkin Trans. 1, 2002, 97–101
99

View Article Online
In summary, several N-acylcarbamates with acyl functions of
the heteroaroyl type have been prepared and initially examined
by cyclic voltammetry with respect to reduction. Of the com-
pounds studied, those based on pyrazine, 2-quinoline and 2-
quinoxaline in particular indicated highly facilitated reduction.
Selected products were cleaved by controlled potential elec-
trolysis above Ϫ1.5 V versus SCE and especially by the mild
reducing agents, activated aluminium and NaBH4.
greenish oil. The yield of crude, essentially pure Boc–NHBzl
was 129.4 mg (96%). Crystallization from n-hexane (decolor-
izing carbon) afforded the analytical specimen as white crystals;
mp 54.0–55.0 ЊC. TLC (toluene–MeCN 2 : 1) and H NMR
showed complete identity with an authentic sample.
1
II. Cleavage by activated aluminium. Activated Al foil.
Aluminium foil (kitchen foil, ∼0.02 mm) was cut into small
pieces (1–2 cm2) and carefully washed with light petroleum and
Et2O. It was then covered with 0.5 mol dmϪ3 NaOH for about
30 s, whereupon small bubbles of gas appeared. The solution
was quickly decanted and the foil was rapidly rinsed three times
with glass-distilled water. A 0.5% solution of HgCl2 was added
and left for 40–50 s, after which time the foil had attained a dark
grey colour. The solution was decanted and the foil was quickly
rinsed, in turn, with glass-distilled water, EtOH and finally with
Et2O (3 times each) and then kept under Et2O.
Experimental
General methods
All mps were measured on a Gallenkamp apparatus and are
uncorrected. TLC analyses were carried out on 0.25 mm thick
precoated silica plates (Merck Fertigplatten Kieselgel 60F254
)
and spots were visualized under UV light. FT-IR spectra were
recorded for KBr disks at a resolution of 4 cmϪ1 on a Mattson
Polaris spectrometer equipped with software for conversion to
% transmission. 1H and 13C NMR spectra were recorded with a
JEOL JMN Ex 400 spectrometer in ∼5% solution at 25 ЊC. All
shifts are given in δ ppm using δH(TMS) = 0 and δC(CDCl3/
DMSO-d6) = 77.02/39.50, respectively, as internal references.
Elemental analyses were performed by Mikro Kemi AB
(Uppsala).
Cleavage of compound 2e. Typical procedure. Recrystallized
2e (312 mg, 1.00 mmol) was dissolved in Et2O (35 cm3) contain-
ing water (1%) and treated with freshly activated Al foil (270
mg, 10 mmol) in small portions in a CO2(g) atmosphere with
rapid stirring at RT. After 3 h, TLC (toluene–MeCN 2 : 1)
indicated complete consumption of 2e and the grayish solid was
filtered off and rinsed repeatedly with Et2O. The combined
filtrate and washings (30 cm3) were washed successively with 1
mol dmϪ3 KHSO4, 1 mol dmϪ3 NaHCO3 and brine (3 × 10 cm3
each) and dried (MgSO4 in the presence of decolorizing
carbon). A white solid weighing 187 mg (90%) was obtained
after meticulous drying at reduced pressure. TLC (Et2O–light
Synthesis of N-benzyl-N-Boc-arenecarboxamides (2)
Synthesis of N-benzyl-N-Boc-pyrazinecarboxamide (2f ).
Typical procedure9b. To a suspension of 1f (6.40 g, 30 mmol)
and Boc2O (7.86 g, 36 mmol) in MeCN (50 cm3) was added
DMAP (183 mg, 1.5 mmol) with stirring, whereupon the amide
dissolved within 20–25 min. The reaction was monitored by
TLC (toluene–MeCN 2 : 1; UV) and was complete within 18 h.
After evaporation of the solvent, the remaining oil was
dissolved in EtOAc–Et2O 1 : 1 (200 cm3) and extracted with 1
mol dmϪ3 KHSO4 and water (25 cm3 each). After drying
(Na2SO4), evaporation gave a solid which was crystallized from
EtOAc–light petroleum furnishing a first crop (7.88 g) of 2f
with mp 73–74 ЊC. From the mother liquor, after concentration,
a second crop (0.63 g) with mp 70–72 ЊC could be obtained;
total yield 91%.
1
petroleum 1 : 2) and H NMR showed complete identity with
an authentic sample.
Cleavage of compounds 2 by activated aluminium under com-
petition conditions. General procedure. The two substrates
(0.10 mmol each) were dissolved in Et2O containing 1% water
(∼5 cm3) at RT under CO2. To the clear solution was added
freshly activated Al [1 equiv. (∼6 mg) or 3 equiv. (∼17 mg)] with
rapid stirring. After 4–6 h, most of the Al had reacted and
the insoluble fine-grained solid was filtered off. The essentially
colourless filtrate was evaporated to complete dryness and the
1
oily residue was examined by H NMR (CDCl3). Integration
was carried out over Boc-Me and/or benzyl-CH2 signals and
molar ratios of the remaining substrates as well as those of
products/starting materials were determined.
Compounds 1a–i and 2a–i. Spectroscopic data and some
synthetic details on all compounds made and studied are
given under expanded experimental in the supporting
information.†
III. Cleavage by NaBH4. (a) Typical procedure with isol-
ation only of Boc–NH–Bn. Compound 2f (313 mg, 1.00 mmol)
in absolute EtOH (8 cm3) was treated with NaBH4 (76 mg, 2.00
mmol) with initial mechanical vibration or rapid stirring. The
mixture became turbid within 10 min, and in this case the
reaction was over after 10–15 min (monitoring by TLC). After 1
h the reaction was quenched by addition of acetone (1 cm3) and
left for another hour, whereupon the mixture was taken to
dryness and the remaining semisolid material partitioned
between Et2O and 1 mol dmϪ3 KHSO4. The organic phase was
washed successively with 1 mol dmϪ3 KHSO4, 1 mol dmϪ3
NaHCO3 and brine (3 times each) and dried (MgSO4). Evap-
oration gave an oil, pure by TLC, which slowly solidified
on drying in vacuo; yield 97%. Recrystallization furnished
glittering flakes, mp 56–56.5 ЊC, in close agreement with most
literature values (48–58 ЊC).
Compounds 3–5 and 8 and 9. The detailed preparation of
these compounds is described in the supporting information.†
Reductive cleavage experiments
I. Cleavage by electrolysis. Cleavage of 2g. Typical
procedure. A two compartment cell for controlled potential
electrolyses was filled with MeCN containing Et4NCl (0.1 mol
dmϪ3) as the supporting electrolyte and Et3NHCl (0.015 mol
dmϪ3) as the proton donor. Recrystallized 2g (253 mg,
0.65 mmol) was added to the cathodic compartment and a cyc-
lic voltammogram was recorded at a sweep rate of 100 mV sϪ1
in order to measure the corresponding peak potential. The
potential was adjusted to a value corresponding to 50 mV lower
than the peak potential measured, and the apparatus switched
on. When the intensity of the current was almost zero, the
reaction mixture (catholyte) was transferred to a round-
bottomed flask and the solvent evaporated at reduced pressure.
The residue was partitioned between 100 cm3 of EtOAc and 50
cm3 of KHSO4 (1 mol dmϪ3). The organic phase was then
washed with KHSO4 (1 mol dmϪ3), NaHCO3 (1 mol dmϪ3) and
brine (3 × 30 cm3 each) and dried (MgSO4 in the presence of
decolorizing carbon). Removal of the solvent left a slightly
(b) Reduction of compound 2a with isolation also of
naphthalene-1-methanol. This experiment is described in the
Supporting information.†
Acknowledgements
U. R. thanks NFR and Magnus Bergvalls Stiftelse for their
generous support and the RSC for a journals grant for inter-
national authors. L. G. acknowledges a grant from TFR. We
wish to acknowledge also the Foundation for Science and
100
J. Chem. Soc., Perkin Trans. 1, 2002, 97–101

View Article Online
9 (a) D. L. Flynn, R. E. Zelle and P. A. Grieco, J. Org. Chem., 1983,
Technology (Portugal) for financial support to the Institute of
Biotechnology and Fine Chemistry (University of Minho).
48, 2424; (b) L. Grehn, K. Gunnarsson and U. Ragnarsson, Acta
Chem. Scand., Ser. B, 1986, 40, 745; (c) L. Grehn, K. Gunnarsson
and U. Ragnarsson, J. Chem. Soc., Chem. Commun., 1985,
1317.
References
10 M. H. Cynamon, S. P. Klemens, T.-S. Chou, R. H. Gimi and J. T.
Welch, J. Med. Chem., 1992, 35, 1212.
11 B. Iselin and R. Schwyzer, Helv. Chim. Acta, 1960, 43, 1760.
12 M. Hudlický, Reductions in Organic Chemistry, ACS Monograph
188, Washington DC, 2nd edn., 1996, pp. 35 (reduction with Al) and
p. 126 (cleavage of sulfonamides).
1 B. R. Brown, The Organic Chemistry of Aliphatic Nitrogen
Compounds, Clarendon Press, Oxford, 1994, ch. 8.
2 (a) T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, Wiley, New York, 3rd edn., 1999, ch. 7; (b) P. J. Kocien´ ski,
Protecting Groups, Thieme, Stuttgart, 1994, ch. 6.
3 Reviews:; (a) V. G. Mairanovsky, Angew. Chem., 1976, 88, 283
(Angew. Chem., Int. Ed. Engl., 1976, 15, 281); (b) M. I. Montenegro,
Electrochim. Acta, 1986, 31, 607.
13 F. Weygand and E. Frauendorfer, Chem. Ber., 1970, 103, 2437.
14 J. O. Osby, M. G. Martin and B. Ganem, Tetrahedron Lett., 1984, 25,
2093 and references cited therein.
4 L. Horner and H. Neumann, Chem. Ber., 1965, 98, 3462.
5 (a) L. Grehn, K. Gunnarsson, H. L. S. Maia, M. I. Montenegro,
L. Pedro and U. Ragnarsson, J. Chem. Res., 1988, (S) 399; L. Grehn,
K. Gunnarsson, H. L. S. Maia, M. I. Montenegro, L. Pedro and
U. Ragnarsson, J. Chem. Res., 1988, (M) 3081; (b) L. Grehn, H. L. S.
Maia, L. S. Monteiro, M. I. Montenegro and U. Ragnarsson,
J. Chem. Res., 1991, (S) 144; L. Grehn, H. L. S. Maia, L. S.
Monteiro, M. I. Montenegro and U. Ragnarsson, J. Chem. Res.,
1991, (M) 1501; (c) H. L. S. Maia, L. S. Monteiro, F. Degerbeck,
L. Grehn and U. Ragnarsson, J. Chem. Soc., Perkin Trans. 2, 1993,
495.
6 (a) B. Nyasse, L. Grehn, U. Ragnarsson, H. L. S. Maia, L. S.
Monteiro, I. Leito, I. Koppel and J. Koppel, J. Chem. Soc., Perkin
Trans. 1, 1995, 2025; (b) B. Nyasse, L. Grehn and U. Ragnarsson,
Chem. Commun., 1997, 1017; (c) B. Nyasse, L. Grehn, H. L. S. Maia,
L. S. Monteiro and U. Ragnarsson, J. Org. Chem., 1999, 64, 7135.
7 (a) B. J. Tabner and J. R. Yandle, J. Chem. Soc. A, 1968, 381; (b)
K. B. Wiberg and T. P. Lewis, J. Am. Chem. Soc., 1970, 92, 7154.
8 U. Ragnarsson, L. Grehn, H. L. S. Maia and L. S. Monteiro, Org.
Lett., 2001, 3, 2021.
15 (a) L. Grehn and U. Ragnarsson, Angew. Chem., 1985, 97, 519
(Angew. Chem., Int. Ed. Engl., 1985, 24, 510); (b) S. K. Davidsen,
P. D. May and J. B. Summers, J. Org. Chem., 1991, 56, 5482; (c)
B. M. Kim, B. E. Evans, K. F. Gilbert, C. M. Hanifin, J. P. Vacca,
S. R. Michelson, P. L. Darke, J. A. Zugay, E. A. Emini, W. Schleif,
J. H. Lin, I.-W. Chen, K. Vastag, P. S. Anderson and J. R. Huff,
Bioorg. Med. Chem. Lett., 1995, 5, 2707; (d ) M. D. Ennis, N. B.
Ghazal, R. L. Hoffman, M. W. Smith, S. K. Schlachter, C. F.
Lawson, W. B. Im, J. F. Pregenzer, K. A. Svensson, R. A. Lewis,
E. D. Hall, D. M. Sutter, L. T. Harris and R. B. McCall, J. Med.
Chem., 1998, 41, 2180; (e) N. Kojima, N. Minakawa and
A. Matsuda, Tetrahedron, 2000, 56, 7909.
16 (a) Y. Takeuchi, M. Kamezaki, K. Kirihara, G. Haufe, K. W. Laue
and N. Shibata, Chem. Pharm. Bull., 1998, 46, 1062; (b) S. Yoshifuji,
K. Tanaka and Y. Nitta, Chem. Pharm. Bull., 1985, 33, 1749; (c)
N. Sakura, K. Hirose and T. Hashimoto, Chem. Pharm. Bull., 1985,
33, 1752; (d ) N. Sakura, K. Hirose and T. Hashimoto, Chem. Pharm.
Bull., 1986, 34, 1506.
17 J. Symerský, P. Malonˇ, L. Grehn and U. Ragnarsson, Acta
Crystallogr., Sect. C, 1990, 46, 683.
J. Chem. Soc., Perkin Trans. 1, 2002, 97–101
101