Copper reagents

The dienone 858 is synthesized by coupling of the alkenyl copper reagent 856 with crotyl chloride (857) in the presence or absence of ZnCl2[731], Tetrabutyllead (859) reacts with benzoyl chloride to afford butyl phenyl ketone[732]. 

A similar distribution of copper reagents can be obtained via the du ect reaction of copper metal with dibromodifluoromethane or bromochlorodifluoromethane in DMF at 85-95 °C [2J2] The oligomerization can be supressed via the addition of alkali metal fluorides to the reaction mixture [272] When HMPAis added to the trifluoromethylcopper solution, decomposition is slowed, and this solution can be used to trifluoromethylate aromatic iodides [270] (equation 143). 

Only few examples of functionalized copper reagents have been prepared The perfluoroallyleopper reagent was prepared via metathesis of the corresponding perfluoroallylcadmium compound [146] (equation 159) Reaction of the allyl... 

The copper species formed depends on the solvent, and three different species were detected by F NMR, although the structure of each species was not elucidated [245 This copper reagent undergoes a variety of coupling reactions with aryl, alkenyl, allyl, and acetylenic halides [244, 245 (equation 162)... 

Reductive coupling reaction of fluonnated vinyl iodides or bromides has been used as a route to fluorinated dienes [246, 247, 248, 249, 250. Generally, the vinyl iodide is heated with copper metal in DMSO or DMF no 1 ntermediate perfluorovmy I-copper reagent is detected. Typical examples are shown m equations 163-165 [246, 247, 249. The X-ray crystal structure of perfluorotetracyclobutacyclooctatetraene, prepared via coupling of tetrafluoro-l,2-diiodocyclobutene with copper, is planar... 

In contrast to the stability exhibited by tlie copper reagents contaimng an a-fluorine, the corresponding a-bromocopper reagent is not stable and decomposes to give an excellent yield of the triene (cumulene) product [254] (equation 167) The ( ) and (Z) cumulenes were separated by chromatography, and the structures were assigned by X ray analysis [254]... 

The perfluoroacetylenic copper compounds undergo coupling reactions with aryl iodides and provide a useful synthetic route to the perfluoroalkyl aryl alkynes [147, 255] (equation 170) Coupling of these copper reagents with the 1-iodo-perfluoroalkynes gives the perfluorodiynes [747 255] (equation 171)... 

The hydrocarbon vinyl iodides behave similarly. The perfluoroacetylenic copper reagents react readily with allyl halides, and preferred attack is at the least hindered position [147, 255] (equation 174). 

With few exceptions chiral Lewis acids are usually moisture-sensitive and require anhydrous conditions, but bench-stable aquo complexes such as [Cu(S,S)-t-Bu-box)(H20)2](SbF6)2 were found to promote the Diels-Alder reaction as effectively as the anhydrous copper reagent. 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

Although furan is usually a poor diene in the Diels-Alder reaction, the chiral copper reagent 24b promotes its asymmetric addition to acryloyloxazolidinone to afford the 7-oxabicyclo[2.2.1]hept-2-ene derivative in high optical purity (Scheme 1.40). Because a retro-Diels-Alder reaction occurs above -20 °C, the reaction must be performed at low temperature (-78 °C) to obtain a high optical yield. The bicy-... 

The chiral copper reagent 24 is an effective catalyst not only for intermolecular, hut also for intramolecular Diels-Alder reactions, as shown in the following schemes (Scheme 1.41, 1,42, 1.43). Synthetically useful octalin and decalin skeletons were synthesized in high enantio- and diastereoselectivity. The synthetic utility of this intramolecular Diels-Alder reaction has been demonstrated hy a short total synthesis of isopulo upone [23, 33d]. 

Better results can be obtained by genetaling die boronate species widi die aid of sodium medioxide. In diis case, satisfactory transmetalalion occurs on treatment widi Cut. Hills, die ftinctionalized copper reagent 55 can be alkyuylaied widi 1-bromo-l-bexyne at -40 C, ftirnisbing die etiyue 56 in 7596 yield (Sdieme 2.15) [32]. 

Organozinc copper reagents have very broad synthetic potential and a number of typical expetimenlal procedures have recently been puhliidaed [99,100],... 

Ttansmetalation of tliioetliets to organocopper compounds can also be performed in some special cases. Tluis, tteatment of the ester 119 with MeyCuLi-LiCN provides the copper reagent 120, which can be treated successfully witli several electrophiles such as allyl bromide ot acid chlorides to afford the expected products such as 121 iScbeme 2.54) [115, 116]. 

For Sb, derived from cydopentanone, a maximum ee of 9096 was adiieved witii tlie bulky copper reagent r-BuPbySiOfCHyl Cu/Lit. EtyO bad to be used as solvent for optimal results in tiiis case, but THF was tiie best solvent in otiiets. Low temperature cnnditions (-100 C, or from -100 to -78 C) were used for all tlie enan-... 

Witli tlie reagent PbCu in tlie presence of tlie additives BF and PBu- , ees of up to 9 596 were obtained, wb de values of up to 8 596 were acliievable witli a vinyl copper reagent. Chiral dienic acetals have also been studied tliree regioisomeric products could be obtained in tliis case as tlie result of Su2, Su2, or Su2" attaclt of tlie organocopper reagent [25]. Mixtures were indeed obtained witli alKyl copper reagents, but PbCu-BF resulted in fotniation of only tlie S 2 and Su2" products, witli selectivity for tlie latter fSclieme 8.12). 

Fifty years ago, Gilman atii copper reagents as sytiflK prepatdtioti of ati orgatiocupt Notietlieless, it took tnote tliai of orgatiocupt. 

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