Cu-catalysed N-arylation of hydrazines with bismuthanes: Synthesis and pinacol or imino-pinacol coupling of 4-formylphenylhydrazines and their phenylimine derivatives

Article abstract of DOI:10.1055/s-2004-835621

Acetal protected 4-formylphenylbismuthane was prepared and used for arylation of trisubstituted hydrazines. Formylphenylhydrazines, obtained after removal of acetal group, were used in coupling reaction to give diols containing two substituted hydrazino m

Full text of DOI:10.1055/s-2004-835621

LETTER
2537
Cu-Catalysed N-Arylation of Hydrazines with Bismuthanes: Synthesis and
Pinacol or Imino-Pinacol Coupling of 4-Formylphenylhydrazines and their
Phenylimine Derivatives
C
u-CatalysedN-A
l
rylation
a
of
H
ydraz
v
ines
w
ithBis
i
muthanes Loog, Uno Mäeorg*
Institute of Organic and Bioorganic Chemistry, University of Tartu, Jakobi 2, 51014, Tartu, Estonia
E-mail: uno.maeorg@ut.ee
Received 25 August 2004
Arylhydrazines and their derivatives (hydrazones, hy-
Abstract: Acetal protected 4-formylphenylbismuthane was pre-
pared and used for arylation of trisubstituted hydrazines.
Formylphenylhydrazines, obtained after removal of acetal group,
were used in coupling reaction to give diols containing two sub-
drazides) bearing an aldehyde group are relatively un-
known compounds. For example, agaritinal, a derivative
of 4-formylphenylhydrazine is often accompanied with
stituted hydrazino moieties and the coupling of corresponding agaritine13 (a derivative of 4-hydroxymethylphenylhydra-
phenylimine derivatives gave corresponding diamines.
zine, which is considered a potential health risk) in mush-
rooms from genus Agaricus, at least one of which
(Agaricus bisporus) is widely cultivated. Formylarylhy-
drazones have been used also as intermediates in the syn-
thesis of compounds with non-linear optical properties,14
hetero-diradicals15 and heterocyclic compounds.16 Other
possible uses of formylphenylhydrazine derivatives in-
clude, for example, in photothermographic materials,17
electrophotographic photoreceptors,18 diagnostic agents
for urobilinogen detection19 and antibiotics.20
Key words: hydrazine arylation, aldehydes, imines, pinacol cou-
pling, diols
This work aims to extend the versatile hydrazines step-
wise substitution strategy with direct introduction of
arylaldehyde functionality and to use such substituted
hydrazinoarylaldehydes and their imine analogues in
pinacol or imino-pinacol coupling reactions.
Preparative methods for formylarylhydrazine derivatives
involve, for example, reduction of 4-cyanophenylhydra-
zine derivatives with DIBALH to the corresponding
aldehydes.15 In another method,14 substituted phenylhy-
drazone is metallated with t-BuLi and then treated with
PhN(Me)CHO. 4-Formylhydrazobenzenes formed as a
result of nontypical alkyl-nitrogen cleavage when acet-
amidomethyl substituted diaryl azocompounds were treat-
ed with KOH in alcohol.21 Also, a few other, more
specific, methods have been described.16,22
Aldehydes play an important role in organic synthesis be-
cause they are easily convertible to different functionality
or provide numerous ways for condensation and coupling
reactions.1 One well-known reaction of aldehydes is the
pinacol coupling that is used to prepare vicinal diols.2 Re-
action of aldehydes with primary amines gives aldimines,
which also can be coupled to form vicinal diamines.3,4a
Vicinal diols and diamines both, especially in the homo-
chiral form, are used as ligands in catalysts, as complex-
ing agents, and as synthetic intermediates.4
Here we describe the synthesis of aryl bismuthane 1 from
4-bromophenyl-1,3-dioxolane23 and its use for arylation
of three substituted hydrazines. The aryl bismuthane 1 is
obtained in good yield via standard aryl Grignard chemis-
try using a slightly modified method described by Combes
and Finet25 under mild conditions in the final step
(Scheme 1).26
The hydrazine alkyl and aryl derivatives are found in
drugs, pesticides, different types of reagents and consti-
tute starting materials for the synthesis of heterocycles.5a
One convenient way to obtain differentially substituted
hydrazines is to use a directed stepwise substitution–
deprotection strategy starting with a suitably protected
hydrazine derivative.5,6 In this strategy, arylbismuthanes
have been used successfully for arylation of hydrazines.7
Arylbismuthanes are quite versatile reagents for aryla-
tion,8–12 but their synthesis is limited to aryl compounds
substituted with groups tolerating lithiation or Grignard
reagent preparations,8b and also the synthesis of arylbis-
muthanes with electron-withdrawing substituents is not so
straightforward, although there are a few examples of
such bismuthanes.12b
Scheme 1 Synthesis of arylbismuthane 1.
Arylation of hydrazines with 1 in the presence of
Cu(OAc)2 and Et3N9d proceeded under mild conditions
and gave good yields for trisubstituted hydrazines27 (see
Table 1, compounds 3a–c).28 When 1,2-diacetylhydrazine
was used, the arylation gave complicated mixture of
unidentified products. Acetal group removal from com-
SYNLETT 2004, No. 14, pp 2537–2540
Advanced online publication: 20.10.2004
DOI: 10.1055/s-2004-835621; Art ID: G33404ST
© Georg Thieme Verlag Stuttgart · New York
2
2
.1
1
.2
0
0
4

2538
O. Loog, U. Mäeorg
LETTER
conditions described by Gansäuer and Bauer32 gave the
corresponding diols 5a–c33 in moderate yields and with
moderate (5a,b) to good (5c) diastereoselectivity.
Long reaction times and moderate yields are probably due
to the bulky substituents in the hydrazino moiety. For ex-
ample, the lowest yield and longest reaction time were ob-
served for cases in which all three substituents in
hydrazine were Boc groups (entry 2). Long reaction times
may also be responsible for the moderate diastereoselec-
tivity observed.35
The coupling of phenylimine derivatives36 7a and 7b to
the corresponding diamines were then investigated. Treat-
ment with Zn/Cu couple31 gave diamines in 71% and ca.
29% yields, respectively, but with no diastereoselectivi-
ty.37
Scheme 2 Arylation of substituted hydrazines with 1 and pinacol
coupling of hydrazinobenzaldehydes 4. Conditions: i) Cu(OAc)2,
Et3N, CH2Cl2; ii) TsOH, THF–H2O; iii) Mn, Cp2TiCl2, 2,4,6-
Me3Py·HCl, THF (or in entry a¢: Zn/Cu, EtOH, D).
It should be noted that attempts to remove two or three
Boc groups attached to one hydrazino moiety in products
5b, 6a, 6b, 8a simultaneously under different deprotection
conditions38 led in all cases to degradation or polymerisa-
tion.39 Hence it is advisable that the hydrazine derivative
into which the 4-formylphenyl group is to be introduced
is selected so that there is no further need for removal of
Boc groups. Alternatively, different protecting groups
(for example Z) should be considered.
pounds 3a–c proceeded in high yields by treatment with
substoichiometric amounts of TsOH in aqueous THF.29
Under these conditions, Boc groups, even on the same
nitrogen in 3b, were not affected.
Treatment of 4a with Zn/Cu couple30 in ethanol (entry a¢)
resulted mainly in the formation of simple reduction prod-
uct 6a.31 Coupling of hydrazinobenzaldehydes under the
In conclusion, we have shown that 4-formylphenyl group
could be introduced under mild conditions and in good
Scheme 3 Synthesis of phenylimine derivatives 7 and their imino-pinacol coupling. Conditions: i) PhNH2, MgSO4, CH2Cl2; ii) Zn/Cu,
EtOH, D.
Table 1 Details for the Reactions in Scheme 2 and Scheme 3a
R1
R2
3
4
5 + 6
7
8
Time
(h)
Yield
(%)
Time
(h)
Yield
(%)
Time
(h)
Yield of 5
(%, dl/meso) (%)
Yield of 6 Time
Yield Time
Yield
(%, dl/meso)
(h)
(%)
(h)
a
Ph
Boc
28
96
3
92
23
29
61
23
65 (4:1)
8 (1:1)
(15)b
23
98
1
71 (1:1)
a¢
b
c
65
22
10
Boc
Ac
Boc
Ac
52
49
94
85
1.5
1
96
92
48 (4:1)
50
26
91
6
ca. 29c (1:1)
51 (10:1)
47d
a Yields are for isolated materials. Ratios of dl/meso isomers were estimated on the basis of C18 HPLC and 1H NMR; dl and meso isomers were
assigned based on signals of benzylic protons in 1H NMR spectra as described in the literature.34
b Yield estimated on the basis of C18 HPLC.
c Calculated on the basis of the yield of isolated material (44%), which contained ca. 15% of starting material 7b.
d Initial yield of raw product was almost quantitative, but the attempts to crystallise the raw product and finally its purification by silica gel
column chromatography lowered the yield considerably.
Synlett 2004, No. 14, 2537–2540 © Thieme Stuttgart · New York

LETTER
Cu-Catalysed N-Arylation of Hydrazines with Bismuthanes
2539
(11) For the use of arylbismuthanes in arylation of hydrazine
derivatives, see ref.7 and ref.10
yields into trisubstituted hydrazines. We have also de-
monstrated that formylphenylhydrazines undergo cou-
pling reaction to diols containing two substituted
hydrazino moieties (5a–c) and the corresponding phe-
nylimine derivatives undergo coupling to corresponding
diamines (8a,b). In principle, numerous other trisubstitut-
ed hydrazines and also secondary amines/amides could be
used as substrates and also bismuthanes of other benz-
aldehyde derivatives could be prepared and used in the
similar manner for arylation.
(12) Arylbismuthanes provide interest not only as arylating
reagents but also as for example: (a) Therapeutic agents:
Matano, Y.; Aratani, Y.; Miyamatsu, T.; Kurata, H.; Miyaji,
K.; Sasako, S.; Suzuki, H. J. Chem. Soc., Perkin Trans. 1
1998, 2511. (b) Building blocks for three-dimensional
organometallics: Murafuji, T.; Nishino, K.; Nagasuke, M.;
Tanabe, A.; Aono, M.; Sugihara, Y. Synthesis 2000, 1208;
and references therein.
(13) (a) Stijve, T.; Pittet, A. Deutsche Lebensmittel-Rundschau
2000, 96, 251; Chem. Abstr. 2000, 133, 134478.
(b) Chulija, A. J.; Bernillon, J.; Favre-Bovin, J.; Kaouadji,
M.; Arpin, N. Phytochemistry 1988, 27, 929.
(14) Gompper, R.; Walther, P. Tetrahedron 1996, 52, 14607.
(15) Ionita, P.; Whitwood, A. C.; Gilbert, B. C. J. Chem. Soc.,
Perkin Trans. 2 2001, 1453.
(16) Slouka, J. Pharmazie 1971, 26, 466.
(17) Yanagisawa, H.; Ho, K. S. Eur. Pat. Appl. EP 1168066,
2002; Chem. Abstr. 2002, 136, 61567.
Acknowledgment
This work was financially supported by the Estonian Science
Foundation (No. 5255). We thank Dr Olga Tšubrik and Mr Aleksei
Bredihhin for obtaining NMR spectra and Dr Ulf Ragnarsson for his
encouragement and long-term support.
(18) Nagata, M.; Kunieda, M.; Kanemaru, T. Jpn. Kokai Tokkyo
Koho JP 2000314972, 2000; Chem. Abstr. 2000, 133,
357222.
(19) Rittersdorf, W.; Rey, H.; Rieckmann, P. S. African ZA
6806903, 1969; Chem. Abstr. 1970, 72, 29743.
References
(1) Larock, R. C. Comprehensive Organic Transformations,
2nd ed.; Wiley: New York, 1999, 1197–1620.
(2) Reviews: (a) Robertson, G. M. In Comprehensive Organic
Synthesis, Vol. 3; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, 563. (b) Gansäuer, A.; Bluhm, H. Chem. Rev.
2000, 100, 2771.
(3) (a) Mercer, G. J.; Sigman, M. S. Org. Lett. 2003, 5, 1591;
and references therein. (b) Alexakis, A.; Aujard, I.;
Mangeney, P. Synlett 1998, 873; and references therein.
(4) For reviews on vicinal diamines, see: (a) Lucet, D.; Le Gall,
T.; Mioskowski, C. Angew. Chem. Int. Ed. 1998, 37, 2580.
(b) Bennani, Y. L.; Hanessian, S. Chem. Rev. 1997, 97,
3161. (c) See also: Matsubara, S.; Hashimoto, Y.; Okano, T.;
Utimoto, K. Synlett 1999, 1411. (d) Reedijk, J. Chem.
Commun. 1996, 801. (e) For vicinal diols see, in addition to
ref.2: Kim, Y. H. Acc. Chem. Res. 2001, 34, 955.
(f) Pietruszka, J.; Witt, A. Synlett 2003, 91.
(5) (a) For a review see: Ragnarsson, U. Chem. Soc. Rev. 2001,
30, 205; and references therein. (b) Mäeorg, U.; Grehn, L.;
Ragnarsson, U. Angew. Chem., Int. Ed. Engl. 1996, 35,
2626.
(6) (a) Brosse, N.; Jamart-Grégorie, B. Tetrahedron Lett. 2002,
43, 249. (b) Tšubrik, O.; Mäeorg, U. Org. Lett. 2001, 3,
2297.
(7) (a) Tšubrik, O.; Mäeorg, U.; Sillard, R.; Ragnarsson, U.
Tetrahedron 2004, 60, 8363. (b) Loog, O.; Mäeorg, U.;
Ragnarsson, U. Synthesis 2000, 1591.
(8) For reviews on arylbismuthanes in combination with copper
salts or metallic copper as N- and O-arylating reagents, see:
(a) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003,
42, 5400. (b) Elliott, G. I.; Konopelski, J. P. Tetrahedron
2001, 57, 5683. (c) Organobismuth Chemistry; Suzuki, H.;
Matano, Y., Eds.; Elsevier: Amsterdam, 2001. (d) Finet, J.-
P. Chem. Rev. 1989, 89, 1487.
(20) Takai, H.; Yoshida, M.; Iida, T.; Matsubara, I.; Shirahata, K.
J. Antibiot. 1976, 29, 1253.
(21) Stodola, F. H. J. Org. Chem. 1972, 37, 178.
(22) (a) Vysochin, V. I.; Barkhash, V. A.; Vorozhtsov, N. N. Zh.
Obsh. Khim. 1969, 39, 1607; Chem. Abstr. 1969, 71,
112563. (b) Russel, G. A.; Yao, C. F. Heteroat. Chem. 1993,
4, 433. (c) Wiley, R. H.; Irick, G. J. Org. Chem. 1959, 24,
1925. (d) Antibiotic XK-90 [N-acetyl-N¢-(3-formyl-4-
hydroxyphenyl)hydrazine] has been produced
microbiologically from Streptomyces chibasis, see ref.20
(23) (a) 2-(4-Bromophenyl)-1,3-dioxolane was prepared from 4-
bromobenzaldehyde (obtained from 4-bromotoluene by
treatment with CrO3/Ac2O)23b in 66% yield (mp 33.5–
34.0 °C).24 (b) Lieberman, S. V.; Connor, R. Org. Synth.
1938, 18, 61.
(24) Hon, Y.-S.; Lee, C.-F.; Chen, R.-J.; Szu, P.-H. Tetrahedron
2001, 57, 5991.
(25) Combes, S.; Finet, J.-P. Synth. Commun. 1996, 26, 4569.
(26) A mixture of 2-(4-bromophenyl)-1,3-dioxolane (8.160 g,
35.6 mmol), Mg powder (0.909 g, 37.4 mmol) and THF (55
mL) was gently warmed to induce the reaction, keeping the
reaction mixture temperature below 40 °C. The reaction
mixture was stirred for 4 h at r.t. and cooled to –45 °C. A
solution of BiCl3 (3.370 g, 10.7 mmol) in THF (55 mL) was
added over the period of 20 min at –45 °C. The mixture was
stirred for 35 min at the same temperature and then allowed
to warm to r.t. Sat. NH4Cl solution and brine were added, the
mixture was filtered through celite and the filter cake was
washed with THF. The organic layer was separated and the
water layer was extracted with Et2O. The combined organic
layer was dried (MgSO4) and concentrated at reduced
pressure. The residue was dissolved in the mixture of EtOAc
and CH2Cl2 and eluted with EtOAc through a short pad of
silica gel. Eluates were concentrated to about 1:3 of initial
volume and about the same volume of hexane was then
added. The precipitate was filtered and dried to give 4.74 g
of light yellow fine crystals (mp 150.5–151.5 °C).
Additional 0.16 g of product was obtained from the mother
liquor by silica gel column chromatography (EtOAc–
hexane). Overall yield 4.90 g (70%, purity by NMR >99%).
1H NMR (200 MHz, CDCl3): d = 4.03 (m, 2 H), 4.10 (m, 2
H), 5.76 (s, 1 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.74 (d, J = 8.2
(9) (a) Shimi, K.; Boyer, G.; Finet, J.-P.; Galy, J.-P. Lett. Org.
Chem. 2004, 1, 34. (b) Chatel, F.; Boyer, G.; Galy, J.-P.
Synth. Commun. 2002, 32, 2893. (c) Sorenson, R. J. J. Org.
Chem. 2000, 65, 7747. (d) Chan, D. M. T. Tetrahedron Lett.
1996, 37, 9013.
(10) (a) Aoki, Y.; Saito, Y.; Sakamoto, T.; Kikugawa, Y. Synth.
Commun. 2000, 39, 131. (b) Barton, D. H. R.; Finet, J.-P.;
Khamsi, J. Tetrahedron Lett. 1987, 28, 887. (c) Barton, D.
H. R.; Finet, J.-P.; Khamsi, J. Tetrahedron Lett. 1986, 27,
3615.
Synlett 2004, No. 14, 2537–2540 © Thieme Stuttgart · New York

2540
O. Loog, U. Mäeorg
LETTER
Colourless oil [purity by NMR >99%, by C18 HPLC
Hz, 2 H). 13C NMR (50 MHz): d = 65.3, 103.9, 128.5, 137.6,
156.3. Treatment of arylbismuthane 1 with TsOH in aq THF
(see ref.29) gave corresponding bismuthane with free
aldehyde groups; 1H NMR and 13C NMR spectra were
identical with those described in ref.12b
(MeOH–H2O, UV 254 nm) >95%].
(32) Gansäuer, A.; Bauer, D. J. Org. Chem. 1998, 63, 2070.
(33) Compound 5a: Off-white solid foam [purity by NMR >97%,
by C18 HPLC (MeOH–H2O, UV 254 nm) >97%, dl/
meso = 80:20]. 1H NMR (200 MHz, CDCl3): d = 1.47 (s, 36
H), 3.04 [br s, -OH(dl)], 4.59 (dl, major) and 4.69 (meso,
minor) (2 × s, 2 H), 6.97–7.50 (m, 18 H). 13C NMR (50
MHz): d = 28.2, 78.4, 82.4, 122.4, 123.0, 125.6, 127.2,
128.6, 137.1, 141.1, 141.4, 153.1. Compound 5b: White
solid foam [purity by NMR >97%, by C18 HPLC (MeOH–
H2O, UV 254 nm) >98%, dl/meso = 80:20]. Compound 6b:
White solid foam [purity by NMR >98%, by C18 HPLC
(MeOH–H2O, UV 254 nm) >97%]. Compound 5c: White
solid foam [purity by NMR >94% (ca. 5% Et2O), by C18
HPLC (MeOH–H2O, UV 254 nm) >96%, by 1H NMR dl/
meso = 10:1]. Compound 6c: White solid foam [purity by
NMR >98%, by C18 HPLC (MeOH–H2O, UV 254 nm)
>96%].
(34) For 1,2-diols see: (a) Tsukinoki, T.; Kawaij, T.; Hashimoto,
I.; Mataka, S.; Tashiro, M. Chem. Lett. 1997, 26, 235; and
references therein. (b) For 1,2-diamines 1H NMR, see:
Eisch, J. J.; Kaska, D. D.; Peterson, C. J. J. Org. Chem. 1966,
31, 453. (c) 13C NMR: Periasamy, M.; Srinivas, G.;
Karunakar, G. V.; Bharathi, P. Tetrahedron Lett. 1999, 40,
7577.
(27) Hydrazine 2a was prepared as described in ref.7b (82%, mp
104.5–105.5 °C). Hydrazine 2b was prepared as described in
ref.5b (78%, mp 109–110 °C).
Preparation of Hydrazine 2c. To the mixture of 1,2-
diacetylhydrazine (0.382 g, 3.30 mmol) and MeCN (10 mL)
were added Boc2O (0.756 g, 3.46 mmol) in MeCN (5 mL)
and then DMAP (0.010 g, 0.083 mmol) in MeCN (0.3 mL).
The mixture was stirred at r.t. for 17 h under argon. The
reaction mixture was then poured into the mixture of sat.
NH4Cl (10 mL) and brine (20 mL) and extracted with Et2O.
The combined organic layer was washed with the mixture of
sat. NH4Cl and brine (1:2), sat. NaHCO3 and brine, dried
(MgSO4) and concentrated. Column chromatographic
separation (silica gel, EtOAc) of the residue gave 2c as
colourless oil (0.365 g, 51%), which crystallised on
standing, mp 104–105 °C (purity by NMR >99%).
(28) Typical Procedure. CH2Cl2 (5 mL) and Et3N (0.21 mL, 1.5
mmol) were added to the mixture of hydrazine (1.0 mmol),
Cu(OAc)2 (0.276 g, 1.5 mmol) and bismuthane 1 (0.985 g,
1.5 mmol) in oven-dried flask under argon. The reaction
mixture was stirred at r.t. For the synthesis of 3b additional
amounts of Cu(OAc)2 and Et3N were added after 22 h and 48
h [respectively 0.186 g, 1.0 mmol + 0.091 g, 0.5 mmol of
Cu(OAc)2 and 0.1 mL, 1.0 mmol + 0.1 mL, 1.0 mmol of
Et3N]. For the synthesis of 3c additional amounts of
Cu(OAc)2 (0.276 g, 1.5 mmol) and Et3N (0.28 mL, 2.0
mmol) were added after 24 h. After indicated time (see
Table 1) Et2O and H2O or in case of 3c also brine were
added. In case of 3a only H2O was added, the mixture was
filtered through celite and the residue was rinsed with
CH2Cl2. The organic layer was separated and the water layer
was extracted with Et2O and in case of 3a also with CH2Cl2
or in case of 3c also with EtOAc. The combined organic
layer was washed with brine, dried (MgSO4) and
concentrated at reduced pressure. The residue was purified
by silica gel column chromatography (EtOAc–hexane).
Compound 3a: Colourless oil (purity by NMR >95%).
Compound 3b: Colourless oil (purity by NMR >97%).
Compound 3c: Pale yellow oil (purity by NMR >98%).
(29) Acetal groups were removed similarly to the procedure
described in ref.24; 0.4 equiv of TsOH were used in solvent
mixture THF–H2O 25:1. Compound 4a: Colourless oil
(purity by NMR >98%). 1H NMR (200 MHz, CDCl3):
d = 1.49 (s, 9 H), 1.52 (s, 9 H), 7.11–7.88 (m, 9 H), 9.94 (s,
1 H). 13C NMR (50 MHz): d = 28.16, 28.20, 82.9, 83.5,
121.2, 122.3, 125.7, 128.7, 130.4, 133.0, 141.0, 146.8,
152.5, 152.7, 190.9. Compound 4b: Colourless crystals, mp
96.5–98.5 °C (purity by NMR >97%). Compound 4c:
Colourless oil (purity by NMR >98%).
(35) Gansäuer and Bauer (see ref.32) found that in order to obtain
good dl-selectivity, the concentration of aldehyde must be
kept low, which was achieved by its very slow addition.
(36) Compounds 7a–c were obtained by treatment of compounds
4a–c with aniline (1.2–2.0 equiv) in CH2Cl2 at r.t. in the
presence of MgSO4 followed by filtration through the pad of
celite and concentration at reduced pressure. Compound 7a:
Slightly yellow viscous oil (purity by NMR >98%).
Compound 7b: Light yellowish solid, mp 133–134 °C
(purity by NMR >99%). Compound 7c: Colourless oil
(purity by NMR >95%).
(37) The Zn/Cu couple was prepared and used as described in
ref.30a; products were purified by silica gel column
chromatography (EtOAc–hexane). Compound 8a (1:1
mixture of dl- and meso-isomers): Colourless oil [purity by
NMR >94% (ca. 4% Et2O), by C18 HPLC (MeOH–H2O, UV
254 nm) >97%]. 1H NMR (200 MHz, CDCl3): d = 1.40–1.57
(m, 36 H), 4.49 [br, 3 H, dl-NCH (1 H) and NH (2 H)], 4.88
(br s, 1 H, meso-NCH), 6.42–7.50 (m, 28 H). 13C NMR (50
MHz): d = 28.2, 61.8 (meso), 63.3 (dl), 82.4, 113.9 (meso),
114.2 (dl), 118.0 (meso), 118.3 (dl), 122.7, 125.6, 127.6,
127.7, 128.6, 129.1, 129.2, 135.4 (meso), 137.0 (dl), 141.0,
141.3, 146.5, 147.0, 153.0. Compound 8b (1:1 mixture of dl-
and meso-isomers): Colourless glass [purity by NMR >82%
(ca. 15% 7b), by C18 HPLC (MeOH–H2O, UV 254 nm)
>86%].
(38) Deprotection conditions for Boc groups which were probed:
(a) CF3COOH in CH2Cl2, see for example: Mäeorg, U.;
Pehk, T.; Ragnarsson, U. Acta. Chem. Scand. 1999, 53,
1127. (b) Aq HCl in CH3CN. (c) BF3·Et2O in HOAc, see:
Hiskey, R. G.; Beacham, L. M. III; Matl, V. G.; Smith, J. N.;
Williams, E. B. Jr.; Thomas, A. M.; Wolters, E. T. J. Org.
Chem. 1971, 36, 488. (d) SnCl4 in EtOAc, see: Miel, H.;
Rault, S. Tetrahedron Lett. 1997, 38, 7865.
(39) Similarly, it has been found that removal of Boc groups from
1,2-di-Boc-1,2-diarylhydrazines under usual conditions
resulted in cleavage of the N–N bond, to give rise to the
corresponding arylamines: Kim, K.-Y.; Shin, J.-T.; Lee, K.-
S.; Cho, C.-G. Tetrahedron Lett. 2004, 45, 117.
(30) For the use of Zn/Cu couple in condensations of imines, see:
(a) Vellemäe, E.; Tubrik, O.; Loog, O.; Mäeorg, S.; Mäeorg,
U. Proc. Estonian Acad. Sci. Chem. 2003, 52, 91; Chem.
Abstr. 2003, 139, 325020. (b) Sergeeva, E. V.; Rozenberg,
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(31) The Zn/Cu couple was prepared and used as described in
ref.30a; products were separated by silica gel column
chromatography (EtOAc–hexane). Compound 6a¢:
Synlett 2004, No. 14, 2537–2540 © Thieme Stuttgart · New York