The hydroboration of olefins with Et(2)BH provides diethyl(alkyl)boranes 2 which readily undergo a boron-zinc exchange with Et(2)Zn providing a range of polyfunctional primary, secondary, and benzylic diorganozincs. The resulting diorganozincs 3 have been reacted with various electrophiles (allylic halides, acid chlorides, alkylidenemalonates, ethyl propiolate, nitroolefins) in the presence of CuCN.2LiCl with excellent yields. With secondary dialkylzincs prepared from diastereomerically pure diethyl(alkyl)boranes, the boron-zinc exchange occurs with loss of stereochemistry. The asymmetric addition of 3 to aldehydes in the presence of the chiral catalyst 55 furnishes optically active polyfunctional secondary alcohols (50 to over 96% ee).
The cross-coupling between sp3-hybridized C centers is an important method for forming carbon-carbon bonds."] The severe limitations of the classical Wurtz reaction led to the development of transition metal catalyzed methods. Copper(1)-catalyzed coupling reactions of organomagnesium halides and organocuprate-mediated substitutions have proven to be especially useful. ['] Yet the drawbacks of these methods such as the necessity of using organomagnesium or organolithium compounds having few functional groups[*. and the need of stoichiometric amounts of copper salts for the formation of cuprates make alternative approaches still desirable. Nickel and palladium catalysts have been used with great success for crosscoupling reactions[41 between unsaturated halides and organotin reagents, but coupling between two sp3 C centers is almost unknown.['] Herein, we report a new nickel-catalyzed crosscoupling reaction between sp3 C centers allowing the synthesis of polyfunctional products.In the course of studies on radical cyclizations using Et,Zn,16] we observed that the unsaturated alkyl bromides l a and l b undergo a fast coupling reaction with Et,Zn in the presence of catalytic amounts of [Ni(acac),] (7.5 mol%) and LiI (20 mol%) i n T H F ( -3 5 C , 4 h f o r l a , 1 8 h f o r 1b)toaffordtheethylated products 2 a and 2b, respectively (81-82% yield; Scheme I ) . group R' is too large or if the double bond is only weakly coordinated to nickel due to steric interactions with the carbon backbone, then dissociation may occur leading to the nickel(1i) complex 9. Dialkylnickel and -palladium complexes are known to have a low tendency for reductive elimination and prefer to undergo transmetalation with the dialklyzinc compound R:Zn leading to the organozinc derivative Low temperatures (-35 " C ) favors the cross-coupling reaction, whereas higher temperatures, which promotes the dissociation of the double bond in 7, lead to mixtures of the cross-coupling product 8 and halogen-zinc exchange product 10. Also under the re- This behavior was u n~s u a l [ '~~~ and led us to suspect that the presence of the double bond in the alkyl iodide was responsible for the easy coupling of la,b.['] To test this assumption we prepared the corresponding saturated bromoalkanes 3 a and 3 b and submitted them to the same reaction conditions. N o coupling reaction was observed at -35 "C, but when the reaction mixture was allowed to warm to room temperature, a nickel-catalyzed bromine-zinc exchange took place leading to the zinc reagents 4 a and 4 b in over 85% yield as shown by iodolysis experiments.[81 The absence of cross-coupling products shows clearly the importance of the double bond in the alkyl iodide for [*I Piof. Dr P Knochel, Dr. A. DeVaSagdydrdJ. Dip1.-Chem. T. Studemann
Mit polyfunktionellen Dialkylzinkverbindungen und primären Alkyliodiden, die eine Doppelbindung in 4‐ oder 5‐Stellung aufweisen. lassen sich bereits bei – 35°C innerhalb weniger Stunden nickelkatalysierte Kreuzkupplungen durchführen, wie unten exemplarisch gezeigt. Dabei entstehen in guten Ausbeuten polyfunktionelle Produkte. NMP N‐Methyl‐2‐pyrrolidinon, Hacac = Acetylaceton, Piv = Pivaloyl .
The presence of a remote unsaturation (double bond, carbonyl group, cyano group) in an alkyl halide facilitates its cross-coupling reaction with various diorganozincs in the presence of Ni(acac)(2) (7.5-10 mol % in THF/NMP mixtures). These results were used to develop a new general cross-coupling reaction between functionalized diorganozincs and alkyl iodides using m- or p-trifluoromethylstyrene as a reaction promotor and Ni(acac)(2) as a catalyst (7.5-10 mol %; -35 degrees C, 5-10 h) leading to a broad range of polyfunctional cross-coupling products.
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