Halides, functionalized dienes

The opportunity of employing various electrophiles and functionalized diene precursors greatly enhances the synthetic potential of p3-allyltitanocenes. Besides aldehydes and ketones, carbon dioxide [11,15,16], acid chlorides [17], imines [11], nitriles [11], isocyanides [11], and organotin halides [18] react to afford the corresponding allylated products after hydrolysis. Examples are given in Scheme 13.8. 

Intramolecular bridging is also observed. For functionalized dienes (e.g., RCH=CHCOCH=CHR), ring closures occur with the formation of thiacyclohexanones, while the related bis alkenylketones result in the formation of the corresponding thiacyc-lohexadienones . Simple thiophene derivatives are formed by insertion of diynes into SCI2 . Similar chemistry is reported for Se halides, and tricyclo thia- and selena ethers are obtained from sequential addition of SCI2 and SeCb to cyclooctatetraene . 

Additions to conjugated systems are further facilitated by some of the features discussed previously e.g., additions to dienes" " and enynes" in the presence of transition-metal catalysts and additions to enynes containing a suitably placed intramolecular function such as hydroxyl. Although uncatalyzed intermolecular additions to alkynylsilanes are not yet demonstrated, additions are seen in the presence of a transition-metal catalysts" and intramolecular additions to alkynylsilane functions by suitably placed internal organomagnesium-halide functions are facile. ... 

Conjugated dienes undergo hydroperfluoroalkylation with perfluoroalkyl iodides and zinc in the presence of titanium catalysts 02 Yields are moderate to good (52-74%) but stereoselectivity is low. From allylic halides functionalized on the a-vinylic position (TMS, carboxylate, phosphonate), additions to terminal alkynes provide functional dienes, used in further synthetic reactions leading to lactones and carboxylic or phosphonic esters.228... 

Palladium-catalyzed coupling reactions of organic halides with olefins or dienes (R. F. Heck, 1979) are broad in scope and simple to carry out. Anhydrous conditions or any special technique are not required and most functional groups are tolerated. 

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

The second pathway is represented by Eqs. (8)—(11). These reactions involve reduction of the Nin halide to a Ni° complex in a manner similar to the generation of Wilke s bare nickel (37, 38) which can form a C8 bis-77-alkyl nickel (17) in the presence of butadiene [Eq. (9)]. It is reasonable to assume that in the presence of excess alkyaluminum chloride, an exchange reaction [Eq. (10)] can take place between the Cl" on the aluminum and one of the chelating 7r-allyls to form a mono-77-allylic species 18. Complex 18 is functionally the same as 16 under the catalytic reaction condition and should be able to undergo additional reaction with a coordinated ethylene to begin a catalytic cycle similar to Scheme 4 of the Rh system. The result is the formation of a 1,4-diene derivative similar to 13 and the generation of a nickel hydride which then interacts with a butadiene to form the ever-important 7r-crotyl complex [Eq. (11)]. 

Coupling of vinyl halides with vinyltin reagents. This cross-coupling can be effected at room temperature in DMF in the presence of (CH,CN)2PdCl, or CLPd[P(C6H5),]2. Pure (E,E)-, (E,Z)-, (Z,E)-, or (Z,Z)-1,3 dienes can be prepared by this reaction, since the geometry of each partner is retained. The reaction tolerates many functional groups. 

The cross-coupling of alkynylzinc halides or fluorinated alkenylzinc halides with fluori-nated alkenyl iodides allows the preparation of a range of fluorinated dienes or enynes - Functionalized allylic boronic esters can be prepared by the cross-coupling of (dialkylbo-ryl)methylzinc iodide 428 with functionalized alkenyl iodides. The intramolecular reaction provides cyclized products, such as 429 (Scheme 109) ° °. In some cases, reduction reactions or halogen-zinc exchange reactions are observed. 

Palladium catalysts that are free of halide ions effect the dimerization and carboxylation of butadiene to yield 3,8-nonadienoate esters. Palladium acetate, solubilized by a tertiary amine or an aromatic amine, gives the best yields and selectivities (equation 57).87 Palladium chloride catalyzes the hydrocarboxylation to yield primarily 3-pentenoates.88 The hydrocarboxylation of isoprene and chloroprene is regio-selective, placing the carboxy function at the least-hindered carbon (82% and 71% selectively) minor amounts of other products are obtained (equation 58). Cyclic dienes such as 1,3-cyclohexadiene and 1,3-cyclooctadiene are similarly hydrocarboxylated. 

Keywords active methylene compound, unsaturated alkyl halide, alumina, potassium tert-butoxide, 4,4-bis-functionalized 1,6-diene, 1,6-diyne... 

Additions to functionalized three-carbon olefins have been studied extensively. We have used methyl acrylate as a standard olefin since it always reacts only at the terminal carbon and the a,/3-double bond in the product is always trans. The stereospecificity of its reactions with vinylic halides varies with structure. The simple 1-halo-l-alkenes with methyl acrylate under normal conditions give mixtures of E,Z- and E,E-dienoates. The reaction is more selective with the bromides than with the iodides and the stereoselectivity increases with increasing triphenylphosphine concentration. This occurs because the excess phosphine displaces the hydridopalladium halide group from the diene 7r-complex before readdition to form the ir-allylic species occurs (see Equation 6). The disubstituted vinylic bromides react stereospecifically with methyl acrylate (4). 

Four-carbon-chain extensions have been very successful with conjugated dienes as the functionalized olefins. We have used a few other compounds also, but they are of limited value, such as N-3-butenylphthalimide. The last compound is only useful with aromatic or certain vinyl halides where mixtures of allylic amines would not be formed. A typical diene example is the reaction of vinyl bromide with butadiene and piperidine which gives E-N-(2,5-hexadienyl)-piper-idine in 70% yield (7). The product of this reaction can be reacted again and used to extend the carbon chains by six atoms (see below). The reactions of conjugated dienes can be used to produce conjugated trienes also (4). 

The benzyne functions as a dienophile towards reactive diene systems. The reactivity of the 9,10-positions in anthracene is well known (Diels-Alder reaction, Section 7.6), and addition of benzyne to 9-bromoanthracene yields the interesting cage-ring alkyl halide 9-bromotriptycene (9-bromo-9,10-o-benzenoanthracene). The reaction is incomplete and some unreacted 9-bromoanthracene remains in the crude reaction products, but may be removed by virtue of its ready conversion into a maleic anhydride adduct in a further Diels-Alder-type reaction. 

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