Cuprate higher order

Cuprate, dibutyl-, lithium, reaction with acetylene, 66, 62 Cuprates, higher order, 66, 57... 

Organometallic substitution of iron-complexed dioxolenes has been reported. The reaction proceeds with net inversion of configuration, the result of a two-step addition-elimination pathway. Dialkyl-cuprates, higher order cyanocuprates and Grignard reagents have all been employed, and sequential dis-... 

Organocopper Lower order cuprate Higher order cuprate... 

A further improvement in the cuprate-based methodology for producing PGs utilizes a one-pot procedure (203). The CO-chain precursor (67) was first functionalized with zirconocene chloride hydride ia THF. The vinyl zirconium iatermediate was transmetalated direcdy by treatment with two equivalents of / -butyUithium or methyUithium at —30 to —70° C. Sequential addition of copper cyanide and methyUithium eUcited the /V situ generation of the higher order cyanocuprate which was then reacted with the protected enone to give the PG. 

The optically active iodide 153 (Scheme 43) can be conveniently prepared from commercially available methyl (S)-(+)-3-hydroxy-2-methylpropionate (154) (see Scheme 41). At this stage of the synthesis, our plan called for the conversion of 153 to a nucleophilic organometallic species, with the hope that the latter would combine with epoxide 152. As matters transpired, we found that the mixed higher order cuprate reagent derived from 153 reacts in the desired and expected way with epoxide 152, affording alcohol 180 in 88% yield this regioselective union creates the C12-C13 bond of rapamycin. 

The conversion of a thiolactone to a cyclic ether can also be used as a key step in the synthesis of functionalized, stereochemically complex oxacycles (see 64—>66, Scheme 13). Nucleophilic addition of the indicated higher order cuprate reagent to the C-S double bond in thiolactone 64 furnishes a tetrahedral thiolate ion which undergoes smooth conversion to didehydrooxepane 65 upon treatment with 1,4-diiodobutane and the non-nucleophilic base 1,2,2,6,6-pentamethylpiperidine (pempidine).27 Regio- and diastereoselective hydroboration of 65 then gives alcohol 66 in 89 % yield after oxidative workup. Versatile vinylstannanes can also be accessed from thiolactones.28 For example, treatment of bis(thiolactone) 67 with... 

Addition of 15-crown-5 to the higher-order cuprate led to a reagent that is totally unrcac-tive towards 2-phenylpropanal even at room temperature18. If, however, boron trifluoride-diethyl ether complex was added as additional ingredient, the reactivity was restored and, furthermore, the Cram selectivity increased to 90 10 (Table 4). Analogous results could be obtained by placing the crown-ether effect within the cuprate itself, as in reagent 10. 

Rate enhancement and an improved stereoselectivity was also found for higher-order cuprates when chlorotrimethylsilane was addedl9. H- and 29Si-NMR studies revealed that higher-order... 

This reagent is perhaps best thought of as a higher-order mixed cuprate of the type (R3Si)2Cu(CN)Li2 (7). 

Another way is to dissolve an alkylcopper compound in an alkyllithium solution. Higher order cuprates can also be prepared, as well as non-ate copper reagents. Metallocenes (see p. 53) are usually made by this method ... 

The reaction has also been used to prepare 1,3-dilithiopropanes" and 1,1-dilithio-methylenecyclohexane" from the corresponding mercury compounds. In general, the equilibrium lies in the direction in which the more electropositive metal is bonded to that alkyl or aryl group that is the more stable carbanion (p. 228). The reaction proceeds with retention of configuration an Sgi mechanism is likely. Higher order cuprates (see Ref. 1277 in Chapter 10) have been produced by this reaction starting with a vinylic tin compound ... 

Scheme 36). Interestingly, the higher order cuprate 206 underwent conjugate addition with only moderate selectivity. This is likely due to the intervention of an electron transfer pathway. Competing electron transfer reactions involving a-alkoxymetal reagents of this type have also been reported by Cohen [81]. 

An important type of mixed cuprate is prepared from a 2 1 ratio of an alkyllithium and CuCN.11 Called higher-order cyanocuprates, their composition is R2CuCNLi2 in THF solution, but it is thought that most of the molecules are probably present as dimers. The cyanide does not seem to be bound directly to the copper, but rather to the lithium cations.12 The dimers most likely adopt an eight-membered ring motif.13... 

R2Cu(CN)Li2 reaction with vie-epoxy mesylatesA higher-order cuprate reacts selectively with the epoxide group of the epoxy mesylate 1 to provide 2 with inversion at C3. Ring closure of 2 furnishes the epoxide 3, which reacts with a second equivalent of the higher-order cuprate to furnish meso-4, with inversion at both C, and C3. This two-step reaction provides a route to acyclic alcohols with useful stereocontrol at both adjacent centers. 

Thienyl(cyano)copper lithium S Cu(CN)Li xhe reagent is obtained by reaction of thiophene with BuLi in THF at - 78° and then with CuCN at - 40°. The reagent is fairly stable and can be stored in THF at - 20° for about 2 months. It is inert, but is readily converted by addition of RLi or RMgX into a higher-order mixed cuprate, which is as efficient as the freshly prepared cuprate."1... 

The use of stannylcuprate reagents is well established.112,113 The reactions occur under mild conditions. They are reversible, and the reactivity and regio- and stereo-selectivity are sensitive to the structure and reaction conditions, as illustrated by the reaction of allene with the lower-order cuprate Bu3SnCuCNLi and, more readily, with the higher order cuprate (Bu3Sn)2CuCNLi (Equation (29)).114... 

A large variety of cuprates are known nowadays. They include heteroleptic derivatives R(Y)CuM (Y = alkynyl, halide, amido, alkoxide, thiolato, phosphide M = Li or Mg), and have found widespread application in organic chemistry. Their syntheses and applications are discussed in the other chapters of this book. In addition, compounds in which the copper to lithium (or magnesium) ratio differs from 1 1 are also known examples are R3CuLi2 and the so-called higher order cyanocuprates introduced by Lipshutz et al. [99]. 

So far, only cuprates with a 1 1 copper/lithium ratio have been considered. Treatment of phenyllithium with various substoichiometric quantities of copper bromide in DMS as solvent afforded so-called higher order cuprates, of which two were characterizable by X-ray crystallography. These have the overall stoichiometries Cu2Li3Ph5(DMS)4 and Cu4Li5Ph9(DMS)4 [114, 115). The structure of the former compound in the solid state is shown in Fig. 1.26. 

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