Alkynes reaction with cuprates

Scheme 4.10 gives some examples of application of alkyne carboalumination in synthesis. The reaction in Entry 1 was carried out as part of a synthesis of the immunosuppressant drug FK-506. The vinyl alane was subsequently transmetallated to a cuprate reagent (see Chapter 8). In Entry 2, the vinyl alane was used as a nucleophile for opening an epoxide ring and extending the carbon chain by two atoms. In Entries 3 to 5, the vinyl alane adducts were converted to vinyl iodides. In Entry 6, the vinyl alane was converted to an ate reagent prior to reaction with formaldehyde. 

Two highly unusual reactions were noted in this study which merit attention. First, the treatment of (59) with cuprate (60) gave rise to 1,2-addition of the alkyne as the only product (67% equation 57). Second, when trifluoromethyl ketone (59) was treated with either the higher or lower order methylcu-prates, the cyanohydrin (61) was isolated in addition to the normal 1,4-addition product (equation 58). 

The basicity of Gilman cuprates is so low that they do not undergo acid/base reactions with acetylene or higher terminal alkynes. Instead, they can add to their C=C triple bond (Fig-... 

The basicity of Gilman cuprates is so low that they do not undergo acid/base reactions with acetylene or higher terminal alkynes. Instead, Gilman cuprates effect the car-bocupration of the C=C triple bond (Figures 13.12 and 13.13). This reaction formally resembles the hydroboration of a C=C triple bond ( see example in Figure 13.10). The regioselectivity also is the same hence, the metal is connected to the Cl center of a terminal alkyne. Finally, the reaction shows the same stereoselectivity as in the case of the hydroboration of a C=C triple bond carbocupration occurs as a cis addition. 

The stannylcupration of alkynes has been widely studied. Reaction of alkynes with lithium bis(tributylstannyl) cuprate leads to r -2-(tri butyl stannyl) vinyl cuprates, which are synthetically equivalent to cis- 1,2-ethylene dianions. Addition of the tin-copper reagent across the triple bond occurs i>7/-stereospecifically, thus providing Z-vinylstannanes. Phenylacetylene reacts with the tin cuprate with a regiochemistry opposite to that of 1-decyne.294 The intermediate cuprates react well with the various electrophiles.295 For example, the reaction with ethylene oxide gives primary alcohols, and further treatment of their />-toluenesulfonates with butyllithium gives 1-substituted cyclobutenes (Equation (120)) 294... 

Alkynes can be transformed into alkenylstannanes by reaction with stannyl-cuprates. It is possible to trap the 1,2-dimetallic alkene species with various electrophiles. The analogous vicinal difunctionalization of alkynyl selenides " has also been reported. A route to trisubstituted alkenes from phenylthioacetylene"" starts with cuprate addition, but a 1,2-metal rearrangment is involved. Enamines are obtained from N-ethynyldiphenylamine. The alkenylcopper intermediate is also reactive toward many electrophiles. Silylcupration of functionalized alkynes may lead to cyclic products by virtue of intramolecular alkylation. ... 

Silylcupration of Alkynes. Higher-order silyl cuprates such as (1) add regioselectively to terminal alkynes in a cis fashion, and the intermediate vinylcopper species (4) may be trapped with electrophiles to give 2,2-disubstituted vinylsilanes (5) (eq 5). Corresponding reactions with the lower-order cuprate of reagent (1) give low yields of regioisomeric vinylsilanes upon protonation. ... 

Reactions via Copper Reagents and Cuprates. The conjugate addition reactions of the copper-derived reagents prepared from PhMe2SiLi, their addition reactions with alkynes and al-lenes, and their use in displacements of aUyl halides and esters are covered in the relevant sections. 

Reaction with Alkynes. The silyl cuprate reacts with alkynes by syn stereospecific metallo-metallation (eq 3). Provided that the cuprate is derived from copper cyanide, the regioselectivity with terminal alkynes is highly in favor of the isomer with the sUyl group on the terminus. The intermediate vinyl cuprate (3) reacts with many substrates, familiar in carbon-based cuprate chemistry, to give overall syn addition of a silyl group and an electrophile to the alkyne. A curious feature of this reaction is that the intermediate (3), although uncharacterized, has the stoichiometry of a mixed silicon-carbon cuprate, and yet it transfers the carbon-based group to most substrates, in contrast to the behavior of mixed silyl alkyl cuprates. 

A. Alexakis, G. Cahiez, and J. F. Normant, Tetrahedron, 1980, 36, 1961. (Z)-Alkenyl cuprate reactions with various electrophiles, e.g., CO2, epoxides, aldehydes, ot,jS-enones, and alkynes. 

The extreme mildness and rapidity with which vinyl zirconocenes undergo transmetallation reactions with cyanocuprate at low temperatures leads directly to the corresponding functionalized mixed cuprate with internal electrophiles. Introduction of an a,/3-unsaturated ketone affords the expected 1,4-adduct in good isolated yield. This simple, one-pot process has been applied to alkynes, which possess a nitrile 2, ester 3 or chloride 4 residues (Scheme 12.4) [5]. 

The reaction of 3-substituted 3-haloallenes with various cuprates, the converse reaction of propargyl derivatives, proceeds in an SN2 manner to form alkynes 69b. Very high anti stereoselectivity is achieved693. 

Scheme 54 shows the synthesis reported by Cox et al. of the pyrazoline compound 198 [98]. The Weinreb amide (e.g., 199) was reacted with a terminal alkyne followed by a reaction of the resulting alkyl ketone (200) with an aryl cuprate to produce the pyrazoline 198. Cox et al. employed the use of microwave technology in this reaction. Kidwai and Misra also employed microwave technology to produce pyrazoline compounds [99]. 

More attractive copper-catalyzed (mediated) transformations of allenes into alkynes were reported by Caporusso and co-workers [27f, 73-75], Allenes 142 were converted into alkynes 143 by treatment with stoichiometric amounts of a cuprate species, as exemplified in Scheme 14.35. The problem of regioselective formation of either alkyne 143 or allene 144 was solved by the proper choice of the organometallic species. Preferential formation of alkynes 143 could be achieved employing cuprates such as R3Cu(CN)ZnCl-LiCl, which are prepared from organozinc compounds. On the other hand, reactions of organomagnesium derived cuprates (R3CuBr)Mg-LiBr mostly provided allenes 144 as major components. 

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