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Relevant academic research and scientific papers

NEW ORGANOCOPPER REAGENTS PREPARED UTILIZING HIGHLY REACTIVE COPPER

Highly reactive copper solutions have been prepared by the lithium naphthalide reduction of copper(I) iodide/trialkylphosphine complexes.These activated copper solutions will react with organic halides under very mild conditions to form stable organocopper reagents.Significantly, the organocopper reagents can contain considerable functionalities such as ester, nitrile, chloride, epoxide, and ketone groups.These functionalized organocopper species undergo many reactions typical of other organocopper species.Intermolecular 1,4-additions, epoxide-opening reactions, and ketone formation with acid chlorides have been successfully achieved.In addition, this methodology has been applied to an intramolecular epoxide-cleavage reaction.The influence of the connecting chain length, substitution pattern, reaction solvent, and CuI/phosphine complex upon the regioselectivity of the intramolecular cyclization is described.

Preparation and Chemistry of the Active Copper Species Derived from CuI*PBu3, CuI*PPh3, and CuCN*nLiX Complexes

The preparation of highly reactive copper by the reduction of CuI*PBu3, CuI*PPh3, and CuCN*nLiX copper(I) complexes with the preformed lithium naphthalenide is described.It was found, for all three Cu(I) complexes, that the reduction temperature proved crucial to reactivity of the zerovalent copper species as measured by the ability of the active copper to undergo oxidative addition to carbon-halogen bonds.The lower the reduction temperature the more reactive the zerovalent copper species becomes.The low-temperature reduction allows for the formation of highly reactive copper from CuCN*nLiX complexes.This active copper species undergoes oxidative addition to alkyl and aryl bromides in high yield to form the corresponding organocopper reagent directly without the need for other organometallic precursors.Moreover, the alkyl and aryl bromides can obtain a wide range of functional groups as they are not affected in the oxidative addition step.The functionalized organocopper reagents derived from CuCN*nLiX based active copper are the reagent of choice in the cross-coupling of acid chlorides to produce ketones as well as the 1,4-addition reaction with enones.The lack of phosphines associated with organocopper reagents stemming from CuCN-based active copper makes product isolation more facile.While the functionalized organocopper reagents derived from CuCN*nLiX complexes provide higher isolated yields in the formentioned reactions, they are not nucleophilic enough to undergo inter- or intramolecular epoxide openings.The use of both CuI*PBu3 and CuI*PPh3 Cu(I) complexes in the intramolecular epoxide openings of aryl bromoepoxides is presented.The regiochemistry, endo vs. exo, was shown to be affected by the Cu(I) complex used to generate the active copper species, the solvent, and the pattern of substitution around the epoxide moiety.The active copper species as well as the resulting organocopper reagents derived from both CuI*PBu3 and CuCN*nLiX were investigated using both 31P and 13C NMR.The data from 31P NMR investigation held some evidence for a highly reduced copper(0)-phosphine complex while the 13C studies of the CuCN*nLiX complexes indicated that these species have limited solubility in THF.

Direct Formation and Reaction of Thienyl-Based Organocopper Reagents

The preparation of a highly reactive zerovalent copper complex by the direct reduction of lithium (2-thienylcyano)cuprate with preformed lithium naphthalenide is described.This active copper species oxidatively adds to carbon-halogen bonds to form organocopper reagents.The ability to directly form the organocopper reagent from organic halides and active copper allows for the incorporation of a wide variety of functionalities to be present in the organic halides and the organocopper reagents.Significantly, this formulation of active copper was able to oxidatively add to allyl chlorides and acetates at low temperatures to allow the direct formation of allylic organocopper reagents without Wurtz-type homocoupling.These functionalized organocopper compounds are able to undergo a variety of reactions, such as cross-coupling with acid chlorides, 1,4-conjugate addition with α,β-unsaturated carbonyl compounds, and intermolecular and intramolecular epoxide-opening reactions.Subsequently, this copper species avoids the use of phosphine ligands affording the product isolation much more convenient than with phosphine-based organocopper reagents.

Two Equivalent Reduction of Copper(I) Complexes; Evidence of an Anionic Copper Species

Reactive copper solutions have been prepared by a cold temperature, two equivalent lithium naphthalenide reduction of copper(I) complexes.One equivalent of organic halides react with one equivalent of the anionic copper to yield organocopper reagents.

Direct Formation of Functionalized Alkylcopper Reagents from Alkyl Halides Using Activated Copper. Conjugate Addition Reactions with 2-Cyclohexen-1-one

Activated copper, prepared by the lithium naphthalide reduction of CuIPR3 complexes, has been shown to readily form stable alkylcopper compounds at low temperatures by direct insertion into carbon-halogen bonds.Alkylcopper reagents containing ester, nitrile, and chloride functionalities have been prepared directly from the corresponding alkyl bromides.These alkylcopper reagents have been used effectively in conjugate additions to 2-cyclohexen-1-one, giving functionalized 3-alkylcyclohexanones in good to excellent yields.This approach allows for functionality previously unavailable in organocopper and cuprate reagents.