Improved preparation of secondary zinc iodides by 1,2-migration of sp3 carbenoids

Article abstract of DOI:10.1055/s-2001-14602

R₂Zn in the presence of NMP or LiBr promotes the intramolecular rearrangement of 1,1-diiodoalkanes via the formation of sp³ secondary zinc carbenoid.

Full text of DOI:10.1055/s-2001-14602

818
LETTER
Improved Preparation of Secondary Zinc Iodides by 1,2-Migration of sp3
Carbenoids
Amal Shibli,a Jos P. Varghese,a Paul Knochel,b Ilan Mareka*
a Department of Chemistry and Institute of Catalysis Science and Technology. Technion-Israel Institute of Technology, Technion City,
32000 Haifa, Israel
b Institute of Organic Chemistry, Ludwig-Maximilians-University, Butenandtstrasse 5-13, 81377 Munich, Germany
Fax (972)-4-823 37 35; E-mail: chilanm@tx.technion.ac.il
Received 6 March 2001
Dedicated fondly to Professor J. F. Normant on the occasion of his 65th birthday
by the NMP providing a more reactive pseudozincate.7
Abstract: R2Zn in the presence of NMP or LiBr promotes the in-
So, we wished to use this efficient and economic new
tramolecular rearrangement of 1,1-diiodoalkanes via the formation
of sp3 secondary zinc carbenoid.
form of activated dialkylzinc (equivalent of zincate deriv-
atives)8 for several different synthetic purposes, and we
report here that these derivatives can be successfully used
for the intramolecular rearrangement of sp3 carbenoids.9
Key words: dialkylzinc, zincate, 1,1-diiodoalkane, secondary orga-
nozinc iodide, sp3 carbenoid, homologation
Indeed, treatment of 1,1-diiodoalkane10 1 with 1.2 equiv-
alents of Et2Zn in THF in the presence of NMP allows io-
dine-zinc exchange at –50 °C to form the corresponding
sp3 secondary zinc carbenoid 2. Then, by warming the re-
action mixture to room temperature, the carbenoid 2 un-
dergoes an intramolecular nucleophilic rearrangement
into the secondary organozinc iodide derivative 3 which
can react with different electrophiles in good overall
yields (Scheme 2 and Table).
The intermolecular reaction between a nucleophilic orga-
nometallic and an electrophilic carbon center represents
one of the widest classes of carbon-carbon bond forming
reaction nowadays. Far less common are intramolecular
variants in which both the nucleophilic and electrophilic
partners are bound to the same metal (intramolecular rear-
rangement of carbenoid). When the metal bears a negative
charge, such reactions are defined as 1,2-metallate rear-
rangements and are relatively well known for the migra-
tion of alkyl groups to sp3-, sp2- and sp-hybridized
carbons.1 Particularly attractive is the rearrangement of -
halo-triorganozincate2 (M = Zn) as well as -alkoxy-alke-
nyl lithio cuprate (M = Cu, Scheme 1).3
R = PhCH2
Br2
Br
4
50%
Ph
I
Et
I
I
Et
Zn
+ Et2Zn
+ EtI
R
R
R
–50 °C
to r.t.
THF/NMP
-50°C
ZnI
I
3
R2
R2
2
1a R = PhCH2
1b R = Bu
R1
R2
E
R1
M
R1
R2
2 E+
Et
R2-E
E+
+
R
L.G
M
E
R2
Scheme 2
Scheme 1
In order to prove the stepwise mechanism, intermediate
zinc carbenoid 2 was trapped with Br2 at -50 °C to get 4.
Although, the , ' bromo iodo derivative 4 was isolated
in a promising 50% yield, minor amounts of dibromoal-
kanes were always present in the crude reaction mixture
(probably formed by degradation of the carbenoid 2 into
carbene and subsequent reaction with Br2).
However, an excess of electrophile is usually required to
compensate the excess of alkyl groups attached to the
metal. When the metal is not negatively charged, no in-
tramolecular rearrangement is observed and only intermo-
lecular reaction occurs between carbenoid and
organometallic derivative4 to give the alkylated and rear-
ranged organometallics as products.5
The formation of a secondary organozinc halide 3 was
checked by halogenolysis (entries 2 to 4 and entry 9),
oxidation11 (entry 6) and, finally, by allylation and 1,4-ad-
dition reactions after transmetallation of the organozinc
halide into an organocopper derivative (entries 7 and 8).12
The presence of NMP is absolutely necessary for the reac-
tion to proceed13 since in pure THF, no homologation was
observed.
It was reported recently by one of us that a polar cosolvent
like N-methylpyrrolidinone (NMP) permitted the 1,4-ad-
dition of R2Zn to enones in the absence of any copper or
transition metal catalyst; named as the uncatalyzed conju-
gate addition reaction.6 R2Zn alone did not react with any
of these enones. The origin of this reaction rate increase in
NMP may result from the ionization of the diorganozinc
Synlett 2001, No. 6, 818–820 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Improved Preparation of Secondary Zinc Iodides
819
As the combination R1 Zn, 2LiBr was also successful for
Table Reaction of 1,1-Diiodoalkanes 1 with Et2Zn in THF/NMP
2
the intramolecular rearrangement, the direct preparation
of this complex was performed by treatment of BuLi with
ZnBr2 in THF at 0 °C to room temperature (path B,
Scheme 3). Then, a solution of 1a or 1b was added at
50 °C and the reaction mixture was warmed to room
temperature to furnish the homologated product, which
was classically isolated as iodide 16 and 17 in 75% and
82% yield, respectively (Scheme 3).16
R12Zn
2 LiBr
+
THF
Path A
I
I
R
2 R1Li
+
ZnBr2
THF
R12Zn, 2 LiBr
–50 °C
2-3h
Path B
R1
R1
–50 °C
to r.t.
Zn
R1
I2
R
+ R1I
R
R
I
I
ZnI
14
15
6 R PhCH2, R1 = Et 75%
16 R = PhCH2, R1 = Bu 75%
17 R = Bu, R1 = Bu 82%
Scheme 3
Here again, the mechanism of the reaction is divided into
two steps; formation of the carbenoid and its intramolec-
ular rearrangement. The same result was obtained by the
reaction of Bu2Zn, 2MgBr2 (2BuMgBr with ZnBr2) and
1a to furnish 16 in 75% yield.
In conclusion, we have reported a unique and straightfor-
ward intramolecular 1,2-rearrangement by the combina-
tion of R2Zn either in the presence of 2 equivalents of
NMP17 or in the presence of 2 equivalents of LiBr18 (or
MgBr2) with 1,1-diiodoalkane. We believe that the reac-
tive species is an activated form of R2Zn (as zincate) but
in which only two alkyl groups are linked to the metal.
The reactivity of these derivatives with different systems
are currently being studied in our laboratory.
Acknowledgement
a) Isolated yields after purification by chromatography on silica gel.
This research was supported by a grant from the G.I.F., the German-
Israeli Foundation for Scientific Research and Development (I-535-
083.05/97) and by the fund for the promotion of research at the
Technion.
Moreover, as we have reported recently that lithium ha-
lides may also modify the Lewis character of the zinc at-
om,14 probably via a zincate species,15 we wanted to check
the behavior of the combination of R2Zn/LiBr in this in-
tramolecular rearrangement.
References and Notes
(1) For a review see a) Kocienski, P. Organic Synthesis via
Organometallics Enders, D.; Gais, H.J.; Klein, W. Ed. Vieweg
1993, 203.
(2) a) Chemla, F.; Marek, I.; Normant, J.F. Synlett 1993, 665
b) Harada, T.; Hara, D.; Hattori, K.; Oku, A. Tetrahedron Lett.
1988, 29, 3821 c) Harada T.; Katsuhira, T.; Oku, A. J. Org.
Chem. 1992, 57, 5805 d) Harada, T.; Katsuhira, T.; Hara, D.;
Kotani, Y.; Maejima, K.; Kaji, R.; Oku, A. J. Org. Chem.
1993, 58, 4897 e) Morken, P.A.; Bachand, P.C.; Swenson,
D.C.; Burton, D.J. J. Am. Chem. Soc. 1993, 115, 5430
Indeed, addition of R1 Zn and 2LiBr in THF to 1a at
2
50 °C also led to the formation of carbenoid 14, which
rearranged cleanly into the secondary zinc iodide 15 and,
after addition of iodine, 6 was isolated in 75% yield (path
A, Scheme 3).
Synlett 2001, No. 6, 818–820 ISSN 0936-5214 © Thieme Stuttgart · New York

820
A. Shibli et al.
LETTER
f) Harada, T.; Kotani, Y.; Katsuhira, T.; Oku, A. Tetrahedron
Lett. 1991, 32, 1573.
(15) Zincate ions prepared from R2Zn and salts have been studied:
a) Kubas, K.H.; Schriver, D.F. J. Am. Chem. Soc. 1970, 92,
1949. b) Schriver, D.F.; Kubas, G.J.; Marshall, J.A. J. Am.
Chem. Soc. 1971, 93, 5076. c) Ashby, E.C.; Beach, R.G.
Inorg. Chem. 1971, 10, 2486. d) Ashby, E.C.; Watkins, J. J.
Inorg. Chem. 1973, 12, 2493. e) Fabicon, R.M.; Pagerski, A.;
Richey, H.G. Jr. J. Am. Chem. Soc. 1991, 113, 6680.
(16) The combination Bu2Zn, 2LiBr undergoes the 1,4-addition to
cyclohexenone, in the presence of TMSCl, in a non-optimized
50% yield.
(17) Typical experimental procedure for Et2Zn in THF/NMP.
To a solution of 1,1-diodo-2-phenylethane (716 mg, 2 mmol)
in THF (10 mL) and NMP (0.19 mL, 2mmol) cooled to
50 °C was slowly added Et2Zn (1.0 M in hexane, 2.4 mmol,
1.2 equiv). The reaction mixture was stirred for 3 hours at
50 °C and then was allowed to warm to 0 °C for 1 hour.
The secondary alkyl zinc iodide formed 3 was then cooled to
50 °C and a solution of I2 (508 mg, 4 mmol, 2 equiv) in THF
(3 mL) was added and then slowly warmed to room
temperature. A saturated solution of NH4Cl (20 mL) was
added and the aqueous layer was extracted with ether. The
combined organic layers were washed with Na2S2O3 (10 mL)
and the organic phases are then stirred for 3 hours in the
presence of few Na2S crystals. The organic layer was once
more extracted with ether and dried over MgSO4. After
evaporation of the solvent, the residue was purified by
chromatography silica gel (solvent; hexane) to give 416 mg of
6 (80% yield).
(3) a) Creton, I.; Marek, I.; Brasseur, D.; Jestin, J.L.; Normant,
J.F. Tetrahedron Lett. 1994, 35, 6873 b) Barber, C.; Bury, P.;
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(4) for some leading references see: a) Sidduri, A.R.; Rozemo,
M.J.; Knochel, P. J. Org. Chem. 1993, 58, 2694. b) Sidduri,
A.R.; Knochel, P. J. Am. Chem. Soc. 1992, 114, 7579.
c) Knochel, P.; Sidduri, A.R. J. Am. Chem. Soc. 1990, 112,
6146. d) Knochel, P.; Jeong, N.; Rozema, M.J.; Yeh, M.C.P.
J. Am. Chem. Soc. 1989, 111, 647.
(5) Hoffmann R.W.; Knopff, O.; Kusche, A. Angew. Chem. Int.
Ed. 2000, 39, 1462.
(6) a) Jones, P.; Reddy, C.K.; Knochel, P. Tetrahedron 1998, 54,
1471. b) Jones, P.; Knochel, P. J. Chem. Soc. Perkin Trans. 1
1997, 3117. c) Reddy, C.K.; Devasagayaraj, A.; Knochel, P.
Tetrahedron Lett. 1996, 37, 4495
(7) Fabicon, R.M.; Pajerski, A.D.; Richey, Jr. H.G. J. Am. Chem.
Soc. 1993, 115, 9333.
(8) For a recent article on zincate derivatives see Musser, C.A.;
Richey Jr., H.G. J. Org. Chem. 2000, 65, 7750.
(9) For a recent use of sp3 secondary zinc carbenoid in organic
synthesis, see: Varghese, J.P.; Knochel, P.; Marek, I. Org.
Lett. 2000, 2, 2849.
(10) a) Aufauvre, L.; Knochel, P.; Marek, I. Chem. Commun. 1999,
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(12) Knochel, P.; Singer, R.D. Chem. Rev. 1993, 93, 2117.
(13) In our standard experiment, the ratio R2Zn/NMP is 1/2 but the
quantity of NMP can be increased without any noticeable
difference.
(18) Typical experimental procedure for R2Zn, 2LiBr in THF.
To a solution of ZnBr2 (495 mg, 2 mmol) in 10 mL of THF was
slowly added n-BuLi (1M solution in hexane, 4.4 mmol, 2.2
equiv) at 40 °C. The reaction mixture was allowed to warm
to room temperature and 1,1-diodo-2-phenylethane (716 mg,
2 mmol) in THF (3mL) was added at 50 °C. After stirring for
1 hour at 40 °C, the reaction mixture was warmed to 0 °C for
an hour. Reaction with electrophiles as well as subsequent
treatment is the same as that the one described in the previous
experimental procedure.
(14) Meyer, C.; Marek, I.; Courtemanche, G.; Normant, J.F.
Tetrahedron 1994, 50, 11665
Article Identifier:
1437-2096,E;2001,0,06,0818,0820,ftx,en;G03901ST.pdf
Synlett 2001, No. 6, 818–820 ISSN 0936-5214 © Thieme Stuttgart · New York