Stereoselective Iodocyclopropanation of Terminal Alkenes with Iodoform, Chromium(II) Chloride, and N,N,N′,N′-Tetraethylethylenediamine

Article abstract of DOI:10.1021/ja0373061

Chemoselectivity of a reagent for (E)-olefination of aldehydes derived by reduction of iodoform with chromium(II) chloride in THF changes markedly by addition of TEEDA (N,N,N-,N-tetraethylethylenediamine), and trans-iodocyclopropanes are produced stereoselectively from terminal alkenes by treatment with the base-added reagent system. The iodocyclopropanation occurs only at terminal double bonds, and di- and trisubstituted double bonds in the same molecules remained unchanged. Such functional groups as alcohol, ether, silyl ether, ester, tertiary amine, and amide groups are compatible with the reaction conditions. Copyright

Full text of DOI:10.1021/ja0373061

Published on Web 10/01/2003
Stereoselective Iodocyclopropanation of Terminal Alkenes with Iodoform,
Chromium(II) Chloride, and N,N,N′,N′-Tetraethylethylenediamine
Kazuhiko Takai,* Shota Toshikawa, Atsushi Inoue, and Ryo Kokumai
Department of Applied Chemistry, Faculty of Engineering, Okayama UniVersity,
Tsushima, Okayama 700-8530, Japan
Received July 15, 2003; E-mail: ktakai@cc.okayama-u.ac.jp
Table 1. Iodocyclopropanation of Alkenesa
Geminal dimetallic organic compounds 1 are employed as
reactive intermediates for organic synthesis.1 The Tebbe reagent,
a typical example of 1, shows nucleophilic reactivity toward
,2
1b
carbonyl compounds to afford their methylenation products. The
dimetallic species 1 of early transition metals are postulated in
equilibrium with the metal-alkylidene complex 2 and MXn+1 (eq
3
1
), and the equilibrium shift is caused by the addition of an
4
appropriate amine. In this Communication, we disclose that the
reactivity of a 1,1-dichromium compound derived from iodoform
and chromium(II) chloride changes markedly by addition of
TMEDA (N,N,N′,N′-tetramethylethylenediamine) or TEEDA
(
N,N,N′,N′-tetraethylethylenediamine), and that trans-iodocyclo-
5,6
propanes are produced stereoselectively from terminal alkenes
by treatment with the base-added reagent system.
Treatment of allyl benzyl ether (3) with a mixture of iodoform
(2 equiv) and chromium(II) chloride (4 equiv) in THF at 25 °C for
24 h afforded (2-iodocyclopropyl)methyl benzyl ether (4) in 32%
yield along with the recovery of 3 in 64% yield (eq 2). The trans:
cis ratio of the produced cyclopropanes was 63:37. Addition of
several amines was examined, and it was found that both TMEDA
and TEEDA accelerate the iodocyclopropanation. For example,
when chromium(II) chloride (4 equiv) was pretreated with TMEDA
a
The reactions were conducted on a 1.0 mmol scale. Iodoform (1.5 mol),
CrCl2 (4 mol), and TEEDA (4 mol) were used per mol of an alkene.
Isomeric ratios were determined by isolation and H NMR spectroscopy.
Iodoform (3 mol), CrCl2 (8 mol), and TEEDA (8 mol) were used per mol
of 10-undecen-1-ol.
b
c
1
(4 equiv) in THF before addition of 3 and iodoform, the reaction
was complete at 25 °C in 3 h, and 4 was obtained in 87% yield
7
(
trans:cis ) 85:15). The yield increased to 97% and the trans:cis
ratio improved to 93:7 by using TEEDA (4 equiv).
h of stirring at 25 °C in 99%, 95%, and 97% yields, respectively.
The selectivity of the iodocyclopropanation is shown with a
substrate having both a terminal and a trisubstituted (or 1,1-
disubstituted) double bond; 5 and 6 were produced in selective
manners, respectively (entries 3 and 4). This reactivity contrasts
with that of the Simmons-Smith zinc carbenoid, which reacts faster
8
The results of the iodocyclopropanation of alkenes with iodoform,
chromium(II) chloride, and TEEDA are shown in Table 1. It is
worth noting that the iodocyclopropanation proceeded smoothly
without the presence of a hydroxy or an alkoxy group near the
double bond (Table 1, entries 1-4), which is necessary for the
with more substituted electron-rich alkenes. The iodocyclopropa-
nation reaction proceeded without affecting the following functional
groups: benzyl and silyl ethers, tertiary amine, ester, and amide
(entries 5, 6, 8-10). It is worth noting that the reaction proceeded
without protecting the hydroxyl group, although 3 equiv of the
reagent was required to obtain a high yield (entry 7). Electron-rich
dodecyl vinyl ether was recovered in 85% yield after being stirred
for 24 h; however, electron-deficient R,â-unsaturated ester 7 reacted
with the reagent to give 8 in 37% yield (entry 11).
5a
cyclopropanation of iodoalkenes mediated with zinc carbenoids.
On the other hand, a steric hindrance around the double bond
affected the yield considerably. For example, terminal alkenes
afforded the corresponding iodocyclopropanes in 89-96% yields;
however, an (E)-disubstituted alkene [(E)-2-dodecene], a 1,1-
disubstituted alkene (2-methyl-1-undecene), and a trisubstituted
alkene (2-methyl-2-dodecene) were recovered unchanged after 24
The increased reactivity toward olefinic double bonds by addition
of TMEDA or TEEDA to the iodoform-chromium(II) chloride
reagent is further demonstrated using terminal alkenes having
12990
9
J. AM. CHEM. SOC. 2003, 125, 12990-12991
10.1021/ja0373061 CCC: $25.00 © 2003 American Chemical Society

C O MMU N I C A T I O N S
Scheme 1. Comparison of the Reactivity in the Presence and
Absence of Diamines
have been no appropriate reagents for simple terminal alkenes which
satisfy both yield and stereoselective requirements. The proposed
method will provide an alternative route to trans-iodocyclopropanes.
Acknowledgment. Financial support by a Grant-in-Aid for
Scientific Research on Priority Areas (No. 14078219, “Reaction
Control of Dynamic Complexes”) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan and from the
Nagase Science Foundation is gratefully acknowledged.
Supporting Information Available: General experimental proce-
dure and characterization data for all compounds in Table 1 and
compounds 14 and 15 (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
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Scheme 2. A Plausible Mechanism
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(
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(
(
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(
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carbonyl groups (Scheme 1). The reagent derived from iodoform
and chromium(II) chloride in the absence of diamines reacted only
with aldehyde and ketone carbonyl groups, and selective iodoole-
fination occurred to give iodoalkenes 9 and 10 in 83% and 74%
yields, respectively. An ester carbonyl group was inert to the
reagent, and 13 was recovered in 94% yield. In contrast, when the
diamines were added to the reaction mixture and the amount of
chromium(II) chloride reduced to one-half of the iodoolefination
reagent, the product distributions changed markedly. Although the
aldehyde 11 gave a complex mixture, the terminal alkenes 12 and
(
7) Effects of additives on the yields and stereoselectivities of 4 are as
follows: Et
NMe , 69% (83:17); i-PrMeN(CH
NCHPhCHPhNMe , 61% (82:18), 2,2′-bipyridyl, 13% (64:36).
(8) Charette, A. B.; Beauchemin, A. Org. React. 2001, 58, 1-415.
9) The amount of CrCl is not important for the chemoselectivity. For
example, treatment of 12 with iodoform (2 equiv) and CrCl (4 equiv)
resulted in iodoolefination, but the yield of 10 decreased to 54% (E:Z )
4:46), and 12 was recovered in 43% yield; 14 was not detected.
3
N, 25% (trans:cis ) 70:30); Me
2
NCH
2 2 2 2 3
NMe , 0%; Me N(CH ) -
2
2
)
2
N(i-Pr)Me, 19% (71:29); DL-Me
2
-
2
(
2
2
5
(
10) When 2-fold amounts of the reagent A were used, 16 was obtained in
13% yield (a diastereomeric mixture) along with 10 in 75% yield (E:Z )
54:46).
13 were selectively converted to the corresponding iodocyclopro-
panes 14 and 15 in 58% and 96% yields, respectively. The dramatic
effect on the reactivity of the reagents derived from iodoform and
chromium(II) chloride, caused by the addition of the diamines,
suggests that different reactive species are generated in the reaction
mixture.9
(11) The reactant 12 was recovered in 27% yield. The iodoolefins 10 and 16
were obtained as byproducts in 3% and 6% yields, respectively.
Cyclopropanation of alkenes can be accomplished by both metal-
carbenoid species and metal-carbene complexes.12 Thus, there are
two possible reaction pathways for the production of iodocyclo-
propanes (Scheme 2). The active species of path A is the chromium-
carbenoid 17, and that of path B is the chromium-carbene species
(
12) Dorwald, F. Z. Metal Carbenes in Organic Synthesis; Wiley-VCH:
Weinheim, 1999; pp 105-119.
(
13) For the formation of cyclopropanes by reductive elimination of metallo-
cyclobutanes, see: (a) Ti: Horikawa, Y.; Nomura, T.; Watanabe, M.;
Fujiwara, T.; Takeda, T. J. Org. Chem. 1997, 62, 3678-3682. (b) Re:
Yang, G. K.; Bergman, R. G. Organometallics 1985, 4, 129-138.
14) The geminal dichromium reagent was generated by stirring iodoform (1.5
(
13
1
9. When a diamine is added to the preformed geminal dichro-
equiv) and CrCl
2
(4 equiv) in THF at 25 °C for 30 min. Treatment of
3
-phenylpropanal with the reagent gave 1-iodo-4-phenyl-1-butene in 70%
mium species 18, the reactivity of the reagent changes and
2
yield (E:Z ) 82:18) after stirring at 25 °C for 30 min. In contrast, when
TMEDA (4 equiv) was added to the geminal dichromium reagent
generated at 25 °C for 1 h, and the mixture was stirred for a further 15
min, treatment of 12 with the new base-added reagent at 25 °C for 2 h
gave 14 in 38% yield (trans:cis ) 80:20) along with 10 and 16 in 1% and
3% yields, respectively. The reactant 12 was recovered in 37% yield.
15) A chromium-alkylidene complex having a TMEDA ligand was isolated,
see: Hao, S.; Song, J.-I.; Berno, P.; Gambarotta, S. Organometallics 1994,
13, 1326-1335.
14
iodocyclopropanation occurs selectively. Therefore, we are tempted
to assume that the chromium-carbene species 1915 could be involved
in the cyclopropanation.
The family of trans-iodocyclopropanes5,6 are good precursors
for constructing cyclopropyl-cyclopropyl and -vinyl carbon skel-
(
etons of such natural products16 as FR-900848 and U-106305 using
Suzuki-Miyaura-type cross-coupling reactions.17 Although the
(16) For a review, see: Donaldson, W. A. Tetrahedron 2001, 57, 8589-8627.
(
17) (a) Charette, A. B.; Giroux, A. J. Org. Chem. 1996, 61, 8718-8719. (b)
iodocyclopropanation of alkenes is an attractive direct approach to
Charette, A. B.; De Freitas-Gil, R. P. Tetrahedron Lett. 1997, 38,
2809-2812.
trans-iodocyclopropanes due to the accessibility of the starting
6
materials, this approach has not been popular. This is because there
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