Vinylation, arylation and alkynylation

The best procedures for 3-vinylation or 3-arylation of the indole ring involve palladium intermediates. Vinylations can be done by Heck reactions starting with 3-halo or 3-sulfonyloxyindoles. Under the standard conditions the active catalyst is a Pd(0) species which reacts with the indole by oxidative addition. A major con.sideration is the stability of the 3-halo or 3-sulfonyloxyindoles and usually an EW substituent is required on nitrogen. The range of alkenes which have been used successfully is quite broad and includes examples with both ER and EW substituents. Examples are given in Table 11.3. An alkene which has received special attention is methyl a-acetamidoacrylate which is useful for introduction of the tryptophan side-chain. This reaction will be discussed further in Chapter 13. 

Entry Indole reactant Reagent, conditions Yield (%) Ref. 

A Heck reactions 1 l-Acetyl-3-bromoindole Methyl acrylate, PdiOAc), Ar,P, EtjN, DMF 50 [1] 

2 l-(Phenylsulfonyl)-3-tn fluorom ethyl- Styrene, Pd(PPh3)2Cl2, EtN(i-Pr), DMF 75 [2] 

7 Ethyl l-Benzylindole-2-carboxylate Methyl acrylate, PdClj, Cu(OAc)2 (at 47% conv.) 84 [71 

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The preparations of alkynes on insoluble supports include alkylations, vinylations, arylations, and alkynylations of other alkynes. Most of these reactions can be realized with either the alkyne or the alkylating agent linked to the support. 

CROSS-COUPLING REACTIONS BETWEEN ORGANOMETALLIC REAGENTS AND VINYL, ARYL AND ALKYNYL HALIDES AND RELATED COMPOUNDS... 

Alkenyl (vinyl), aryl, and alkynyl carbocations are particularly unstable with respect to alkyl carbocations. Let s compare the isopropyl cation with the iso-propenyl cation. In the latter, the central C has two cr bonds, one it bond, and one empty orbital, so it is sp-hybridized (linear). Both ions are stabilized by the C(sp3)-H cr bonds of the CH3 group on the right. In the isopropyl cation there is an additional interaction with C(sp3)-H cr bonds on the left, whereas in the isopropenyl cation there is an additional interaction with C(sp2)-H cr bonds on the left. Because C(sp2) orbitals are lower in energy than C(sp3) orbitals, the... 

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

Many valuable reviews of the chemistry of these species are given in the new book Dicoordinated Carbocations An introduction by Grob " is followed by reviews of various theoretical studies of vinyl cations, their gas-phase chemistry, their generation by nuclear decay, and their NMR spectroscopic characterization. Vinyl cation production by addition to acetylenes and allenes, by solvolysis, and photolytically are covered, together with the chemistry of the species generated in these various ways. The next chapter deals with the synthetic applications of vinyl cations,and alkynyl and aryl cations are covered in the last chapter. A review of the NMR spectroscopic and quantum-chemical investigation of vinyl cations in superacid media (also of dienyl and 1-cyclopropylvinyl cations) is published separately,as is a review of alkynylcar-... 

Chromium adds oxidatively not only to vinylic iodides, but also to allylic, aryl, and alkynyl iodides, as well as to CHE (see Chap ter 13).18 The corresponding triflates can be employed equally well. On the other hand the reactivity of bromides and chlorides is usually too limited. Reaction is carried out in the polar aprotic sol vent DMF because this is capable of dissolving both of the salts, and homogeneous conditions accelerate the reaction. 

R. Rossi, A. Carpita, F. Beilina, Palladium- and/ or copper-mediated cross-coupling reactions between 1-alkynes and vinyl, aryl, 1-alkynyl, 1,2-propadienyl, propargyl and allylic halides or related compounds A review, Org. Prep. Proced. Int. 1995, 27, 127-160. 

Aryl and alkynyl carbocations are even less stable than 1° vinyl and methyl cations because they can t rehybridize to make an empty C(p) orbital. In fact, both aryl and alkynyl carbocations can be generated only under very special circumstances and with the best of leaving groups (e.g., N2). 

Allylic phosphates have become especially attractive and popular electrophilic coupling partners toward nonracemically ligated copper species capable of delivering their covalently bound residues in an enantiocontrolled Sn2 sense. Remarkably, the technologies have advanced to the state where carbon sp (alkyl), sp (vinyl, aryl), and even sp (alkynyl) residues on boron are all transferrable via copper in the desired fashion, and where both yields and ee s (or dr s), for the most part, are impressive. 

Many reviews have been published in the last few years on the applications of the Hiyama cross-coupling reaction in organic synthesis. In general, preparation of biaryls or heterobiaryls is the most common application of this reaction since new methodology development is based on examples of these. The most prevalent applications of the aryl and heteroaryl halides with organosilane precursors involve reactions such as vinylations, alkenylations, and alkynylations. The reader is encouraged to consult these key reviews. This section will describe some of the more recent applications published in the last few years. 

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