Stereoselective preparation of functionalized alkenylmagnesium reagents via an iodine-magnesium exchange reaction

Full text of DOI:10.1021/jo981941l

1
080
J . Org. Chem. 1999, 64, 1080-1081
Communications
Ster eoselective P r ep a r a tion of
Sch em e 1
F u n ction a lized Alk en ylm a gn esiu m Rea gen ts
via a n Iod in e-Ma gn esiu m Exch a n ge
Rea ction
†
‡
Mario Rottl a¨ nder, Laure Boymond,
G e´ rard Cahiez,*,‡ and Paul Knochel*,†
Ta ble 1. P r od u cts of Typ e 3 Obta in ed a fter Qu en ch in g
F u n ction a lized Alk en ylm a gn esiu m of Typ e 2 P r ep a r ed
via a n Iod in e-Ma gn esiu m Exch a n ge of th e Iod oa lk en es
of Typ e 1 w ith i-P r MgBr or i-P r 2Mg
Fachbereich Chemie der Philipps-Universit a¨ t Marburg,
Hans-Meerwein-Strasse, D-35032 Marburg, Germany,
and Ecole Sup e´ rieure de Chimie Organique et Min e´ rale,
D e´ partment de Chimie 13, Boulevard de l’Hautil,
F-95092 Cergy-Pontoise, France
Received September 25, 1998
Organomagnesium reagents are versatile organometallic
reagents that have found wide applications.1 The high
reactivity of the carbon-magnesium bond precludes the
presence of many functionalities in these organometallics.
However, low-temperature Grignard syntheses should allow
the generation of polyfunctional organomagnesium reagents
since they do not react to a great extent at -78 °C with2
functional groups such as esters, amides, or nitriles.
Unfortunately, the low-temperature insertion of activated
3
magnesium (Rieke-Mg) is inhibited by these functionalities.
4
Recently, we have shown that polyfunctional aryl iodides
bearing an ester or nitrile function undergo a low-temper-
5
ature iodine-magnesium exchange in the presence of
i-PrMgBr or i-Pr2Mg. However, typical alkenyl iodides are
inert under these reaction conditions. Herein, we wish to
report reaction conditions allowing the stereoselective gen-
eration of alkenylmagnesium reagents as well as applica-
tions of this exchange reaction in solid-phase synthesis. In
strong contrast to functionalized aryl iodides for which the
iodine-magnesium exchange was complete using a stoichio-
metric amount of i-PrMgBr at -20 to -40 °C, alkenyl iodides
proved to be far less reactive. No exchange reaction was
observed with i-PrMgBr under these conditions. The reaction
of (E)-iodooctene (1a ) with i-Pr2Mg (1.1 equiv) requires a
reaction time of 18 h at 25 °C for complete conversion to
the corresponding (E)-octenylmagnesium derivative (2a ).
After treatment with tosyl cyanide (-78 °C, 5 h), the
corresponding nitrile 3a was obtained in 71% isolated yield
as only one stereoisomer showing that the iodine-magne-
†
Fachbereich Chemie der Philipps-Universit a¨ t Marburg.
Ecole Sup e´ rieure de Chimie Organique et Min e´ rale.
‡
(1) (a) Silverman, G. S.; Rakita, P. E., Eds. Handbook of Grignard-
Reagents; Marcel Dekker: 1996. For recent applications, see: (b) Klos, A.
M.; Heintzelman, G. R.; Weinreb, S. M. J . Org. Chem. 1997, 62, 3758. (c)
Taber, D. F.; Green, J . H.; Geremia, J . M. J . Org. Chem. 1997, 62, 9342. (d)
Hayashi, Y.; Shinokubo, H.; Oshima, K. Tetrahedron Lett. 1998, 39, 63. (e)
Heron, N. M.; Adams, J . A.; Hoveyda, A. H. J . Am. Chem. Soc. 1997, 119,
a
Reaction conditions for the iodine-magnesium exchange reac-
b
tion with i-PrMgBr or i-Pr2Mg. Key: (A) tosyl cyanide; (B)
6
205. (f) Houri, A. F.; Xu, Z.; Cogan, D. A.; Hoveyda, A. H. J . Am. Chem.
benzaldehyde; (C) diphenyl disulfide. c Isolated yields of analyti-
cally pure product showing a stereomeric purity of the double bond
Soc. 1995, 117, 2943.
(2) Rieke, R. D.; Xiong, H. J . Org. Chem. 1991, 56, 3109.
(3) Burns, T. P.; Rieke, R. D. J . Org. Chem. 1987, 52, 3674.
(4) Boymond, L.; Rottl a¨ nder, M.; Cahiez, G.; Knochel, P. Angew. Chem.
>
99%.
1
998, 110, 1801; Angew. Chem., Int. Ed. Engl. 1998, 37, 1701.
sium exchange on alkenyl iodides proceeds with complete
retention of configuration of the double bond (Scheme 1 and
Table 1). Similarly, the reaction of 2a with benzaldehyde
provides only (E)-1-phenyl-2-nonenol (3b; entry 2 of Table
(5) For a few examples of halogen-magnesium exchange reactions: (a)
Villieras, J . Bull. Soc. Chim. Fr. 1967, 1520. (b) Paradies, H. H.; G o¨ rbing,
M. Angew. Chem. 1969, 81, 293; Angew. Chem., Int. Ed. Engl. 1969, 8, 279.
(c) Smith, C. F.; Moore, G. J .; Tamborski, C. J . Organomet Chem. 1971, 33,
C21. (d) Cahiez, G.; Bernard, D.; Normant, J . F. J . Organomet. Chem. 1976,
1
) in 60% isolated yield. The reaction of a functionalized
1
1
2
1
13, 107. (e) Seyferth, D.; Lambert, R. L. J . Organomet. Chem. 1973, 54,
234. (f) Redwane, N.; Moreau, P.; Commeyras, A. J . Fluorine Chem. 1982,
0, 699. (g) Furukawa, N.; Shibutani, T.; Fujihara, H. Tetrahedron Lett.
987, 28, 5845. (h) Nishiyama, H.; Isaka, K.; Itoh, K.; Ohno, K.; Nagase,
alkenyl iodide like (E)-5-chloro-1-iodopentene (1b) with i-Pr2-
Mg is complete after 7 h at 25 °C, furnishing after respective
treatment with tosyl cyanide or benzaldehyde the stere-
ochemically pure (E)-products 3c and 3d in 72% and 62%
H.; Matsumoto, K.; Yoshiwara, H. J . Org. Chem. 1992, 57, 407. (i) Bolm,
C.; Pupowicz, D. Tetrahedron Lett. 1997, 38, 7349.
1
0.1021/jo981941l CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/27/1999

Communications
J . Org. Chem., Vol. 64, No. 4, 1999 1081
Sch em e 2
Sch em e 3
3
).10 In the absence of NMP, a reaction time of 2.5 days was
isolated yields (>99% E). The presence of an oxygen-
required to complete the exchange reaction for 1g and 4 h
for 1h .
6
functionalized directing group should facilitate the iodine-
11
magnesium exchange. Therefore, we have examined the
In summary, we have shown that highly functionalized
alkenylmagnesium halides can be prepared at low temper-
ature via an iodine-magnesium exchange performed with
i-PrMgBr or i-Pr2Mg. Under these conditions, functional
groups such as a cyanide, a carbamate, or even an ethyl ester
are tolerated, and reactions with electrophilic functionalities
such as an aldehyde, tosyl cyanide, or diphenyl disulfide
proceed in good yields. This method is also suitable for
solid-phase organic synthesis and should find applications
in combinatorial chemistry.
reaction of polyfunctional 3-iodoallylic ethers such as 1c-f
(
Scheme 2 and Table 1). The readily available (Z)-3-iodoal-
7
lylic ether 1c was treated at -70 °C with i-PrMgBr for 12
h leading to a quantitative iodine-magnesium exchange
reaction. The resulting alkenylmagnesium derivative was
quenched with benzaldehyde, affording the expected (Z)-
unsaturated alcohol 3e (95% yield; >99% Z). Remarkably,
the related iodoallylic ethers 1d and 1f bearing a functional
group like a cyanide or ethyl ester and the iodoallylic
carbamate 1e undergo a clean formation of the correspond-
ing polyfunctional alkenylmagnesium reagents. After being
quenched with electrophiles such as benzaldehyde, diphenyl
disulfide, or tosyl cyanide, the desired products 3f-k were
obtained in 64-91% yield (>99% Z)8 (see Table 1). The
iodine-magnesium exchange also opens the way for the
preparation of alkenylmagnesium reagents for solid-phase
12
Ackn owledgm en t. We thank the Deutsche Forschungs-
gemeinschaft (SFB 260, Leibniz program), the BMBF
program (03 D 0056 2), and BASF AG for generous support.
Su p p or tin g In for m a tion Ava ila ble: Characterization data
of compounds 3a -m .
9
synthesis. Thus, the treatment of the resin-attached (Z)-
J O981941L
alkenyl iodides 1g and 1h with i-PrMgBr (10 equiv) in a
(
10) HPLC-purity (UV, 254 nm, RP 18, CH
3 2
CN/H O (0.1% TFA) gradient
4
0:1 THF/NMP mixture at -40 °C for 1 h followed by the
5
-100% CH CN). Chemical yield 85% based on loading of the resin.
3
addition of benzaldehyde (ca. 15 equiv) furnished after
cleavage from the resin (1:9 TFA/CH2Cl2, rt, 15 min) the 2,5-
dihydrofuranes 3l and 3m with 98 and 97% purity (Scheme
(
11) For theoretical studies on the origin of solvent acceleration in metal-
halogen exchange reactions: J edlicka, B.; Crabtree, R. H.; Siegbahn, P. E.
M. Organometallics 1997, 16, 6021.
(12) Typical Procedure for the Preparation of a Polyfunctional Alkenyl-
magnesium Intermediate and Its Reaction with Benzaldehyde. Preparation
of (Z)-4-(4-carbethoxybenzyloxy)-1,3-diphenyl-2-butenol (3j). To a stirred
solution of (Z)-3(4-carbethoxybenzyloxy)-2-phenyl-1-iodopropene (1f; 700 mg,
1.66 mmol) in THF (4 mL) was added a solution of i-PrMgBr in THF (3.90
mL, 3.32 mmol; 0.85 M) at -85 °C. The reaction mixture was allowed to
warm to -70 °C and was stirred overnight. Benzaldehyde (0.48 mL, 4.65
mmol) was added in THF (1.5 mL), and the reaction mixture was worked
up after 4 h at -50 °C. The crude product obtained after evaporation of the
(
(
(
6) Snieckus, V. Chem. Rev. 1990, 90, 879.
7) Duboudin, J . G.; J ousseaume, B. J . Organomet. Chem. 1979, 168, 1.
8) The retention of the double bond is proven by the iodinolysis of the
alkenylmagnesium reagent derived from the iodoallylic ether 1c, which gave
exclusively the starting material back (>99% Z).
(9) (a) Balkenhohl, F.; v. d. Bussche-H u¨ nnefeld, C.; Lansky, A.; Zechel,
C. Angew. Chem. 1996, 108, 2437; Angew. Chem., Int. Ed. Engl. 1996, 35,
288. (b) Fr u¨ chtel, J . S.; J ung, G. Angew. Chem. 1996, 108, 19; Angew.
Chem., Int. Ed. Engl. 1996, 35, 17.
2
2 2
solvent was purified by flash chromatography (CH Cl /ether 95:5), affording
3j (528 mg, 79% yield) as a colorless oil.