set of novel examples of counterintuitive addition of enolate
anions to simple olefins. With these results in hand, we
conjectured about the use of the γ-zincated hydrazone species
for further synthetic elaboration and found that the aerobic
oxidation of gem-Zn/Sn dimetallic species 3 affords the
pyrrole derivatives 4 with high efficiency.7
Table 1. One-Pot Synthesis of 1-(Dimethylamino)-1H-pyrroles
via gem-Zn/Sn Dimetallic Speciesa
The synthesis starts with the zincated hydrazone 2, which
can be generated from the corresponding hydrazone 1 as
previously reported5,6 or by a simplified new procedure
(treatment of a lithiated hydrazone with BuZnI, Scheme 1).
We found that the use of the BuZn countercation (equally
useful are MeZn and t-BuZn) is mandatory, as hydrazone
anions with a ZnBr or Li countercation were inert to
tributylvinylstannane. Zincated hydrazone 2 added smoothly
at 30 °C to give dimetallic adduct 3, which, upon hydrolysis,
afforded the corresponding γ-stannylhydrazone 5 in good
yield (column 3 in Table 1). Dimetallic species 3 was found
to be perfectly stable at room temperature for a few days
under nitrogen. The vinylstannane reacted smoothly also with
hydrazone 1c (entry 3), which does react with vinylmagne-
sium bromide.5,6 The zincated hydrazones derived from a
cyclic ketone also react with the vinylstannane to afford 3
(entries 4-6).
The reaction took place in such a manner that it gives
exclusively a gem-Zn/Sn dimetallic product rather than a
vicinal dimetallic one.9 In no cases could we find the
occurrence of a tin-zinc exchange reaction on the vinyl-
a The reactions were carried out according to the experimental procedure
described in the footnote 8 and the Supporting Information. Excess
vinylstannane (1.5-2.0 equiv) was used. b Isolated yield based on hydrazone
1. c Carbozincation was carried out using BuZnI. See footnote 8. d Car-
bozincation was carried out as previously reported (refs 5 and 6).
(4) Nakamura, E.; Kubota, K. J. Org. Chem. 1997, 62, 792-793.
(5) Kubota, K.; Nakamura, E. Angew. Chem., Int. Ed. Engl. 1997, 36,
2491-2493. Nakamura, E.; Sakata, G.; Kubota, K. Tetrahedron Lett. 1998,
39, 2157-2160.
(6) Nakamura, E.; Kubota, K.; Sakata, G. J. Am. Chem. Soc. 1997, 119,
5457-5458. Nakamura, E.; Kubota, K. Tetrahedron Lett. 1997, 38, 7099-
7102.
stannane.10 For all the products of the present reaction, the
stereochemistry of the dimethylamino moiety of hydrazone
in 5 was anti to the 2-stannylethyl side chain.11
Exposure of adduct 3 in situ to oxygen at -45 °C and
aging of the mixture under nitrogen at 0 °C to room
temperature for several hours afforded directly 2,3-disubsti-
tuted 1-(dimethylamino)-1H-pyrrole 4. Optimization of the
cyclization conditions necessitated considerable experimenta-
tion, which revealed that removal of the butyl group from 3
by addition of 1 equiv of ZnCl2 prior to aerobic oxidation
was necessary. The results of one-pot synthesis of 1-(di-
methylamino)-1H-pyrroles are shown in Table 1. It is rather
remarkable that in situ transformation involving quite a
(7) Although tributylvinylsilane and triphenylvinylsilane also react with
the zincated hydrazone as reported previously,6 the rate of carbozincation
reaction is considerably slower than that of vinylstannanes. In addition, the
oxidative conversion of the resulting gem-Zn/Si dimetallic product to pyrrole
was much less effective than the gem-Zn/Sn dimetallics. For a prior work
on the oxygen oxidation of zinc-tin organometallics, see: Knochel, P.;
Xiao, C.; Yeh, M. C. P. Tetrahedron Lett. 1988, 29, 6697-6700.
(8) Carbozincation procedure using BuZnI: To a solution of 2-me-
thylheptan-3-one N,N-dimethylhydrazone (1b) (0.21 mL, 1.0 mmol) in dry
ether was added t-BuLi (1.52 M in pentane, 0.66 mL, 1.0 mmol) at -78
°C, and the mixture was stirred at 0 °C for 6.5 h. A solution of BuZnI
(1.04 M in THF, 0.96 mL, 1.0 mmol) was added to a suspension of lithiated
hydrazone at 0 °C, and the resulting solution was stirred for 1.5 h at that
temperature. Tributylvinylstannane (0.58 mL, 2.0 mmol) was added at 0
°C, and the mixture was stirred at 30 °C. After 44 h, a pH-6.9 standard
buffer solution was added. Aqueous quenching of the resulting adduct 3b
gave an oil (0.871 g), which was purified on silica gel to obtain the adduct
5b (0.323 g, 66% yield). Synthesis of 1-(dimethylamino)-1H-pyrrole: To
gem-Zn/Sn dimetallic 3b prepared from hydrazone 1b (0.4 mmol) was added
an ethereal solution of ZnCl2(0.40 mmol) at 0 °C. The reaction mixture
was cooled to -45 °C and exposed to a dry oxygen atmosphere for 4.5 h.
After removal of excess oxygen by degassing, the reaction mixture was
stirred for 13 h at 0 °C and then filtered through a pad of silica gel to
afford a crude product as a colorless oil (214 mg). Purification on silica
gel afforded the substituted pyrrole 4b (60 mg, 0.31 mmol) in 77% yield.
(9) For theoretical analysis of regiochemistry of carbometalation, see:
Nakamura, E.; Miyachi, Y.; Koga, N.; Morokuma, K. J. Am. Chem. Soc.
1992, 114, 6686-6692.
(10) Unreacted vinylstannane was recovered quantitatively.
(11) Syn stereochemistry of the hydrazone products tentatively assigned
in our previous reports (refs 4-6) should be corrected to be anti. Note that
the starting lithiated hydrazone is in syn stereochemistry, and it reacts with
an alkyl halide with retention of the syn stereochemistry. Collum, D. B.;
Kahne, D.; Gut, S. A.; DePue, R. T.; Mohamadi, F.; Wanat, R. A.; Clardy,
J.; Van Duyne, G. J. Am. Chem. Soc. 1984, 106, 4865-4869.
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Org. Lett., Vol. 1, No. 10, 1999