Alkene derivatives alkenyl halides

The Pd(0)-catalyzed reactions of propargylic compounds so far discovered can be classified into four types, I, II, III, and TV, from a mechanistic viewpoint. The allenyl intermediate complex 8 undergoes three types of transformation, depending on reactants. The reactions of Type I proceed by insertion of unsaturated bonds into the a-bond between palladium and sp carbon in 8. This a-bond has a reactivity similar to the a-bond formed by the oxidative addition of alkenyl halides to Pd(0) in the Heck reaction [3]. Therefore, reactions similar to those observed in the Heck reaction are expected to occur witli the intermediate 8. Alkenes and carbon monoxide are known to insert into the palladium-carbon a-bond. The allene derivatives 9 are formed by these reactions (Scheme 11.3). 

Coupling reactions of alkyl boranes, formed by hydroboration of alkenes, with unsaturated halides (or triflates or phosphonates) is possible, and this reaction is finding increasing use in synthesis. For example, coupling of the alkyl borane derived from hydroboration (with 9-borobicyclo[3.3.1]nonane, 9-BBN) of the alkene 200 with the alkenyl iodide 201 gave the substituted cyclopentene 202, used in a synthesis of prostaglandin Ei (1.205). This type of B-alkyl Suzuki coupling reaction is very useful for the synthesis of substituted alkenes. 

There has been a full account of the synthesis of the 2 -stannylated alkene 135 (X = SnBua) by base-induced stannyl migration from C-6 (see Vol. 32, p. 275), and the application of this compound to the preparation of the alkenyl halides 135 (X = Cl, Br, I), and products with carbon substituents at C-2 through Stille couplings. Reaction of di-O-acetyl-L-rhamnal with silylated thjmiine gave the 2 -enopyranosyl nucleoside by allylic rearrangement, as a mixture of anomers. A paper discussing a glycal substituted at C-3 with a nucleobase is mentioned in Chapter 10, and a 3 -ene derived from thymidine is mentioned in Section 17. 

A chromium carbene generated in situ from CrG2 and a dihaloalkyl derivative, has been utilized to form a variety of ( )-disubstituted alkene compounds (480). The gener reaction is summarized in equation (110). Alkenyl halides, sulfides and silanes, as well as dialkyl-substituted alkenes, have been synthesized by this method. 

Several independent protocols using a combination of transition metal-catalyzed stereoselective hydrosilylation, such as palladium-catalyzed crosscoupling sequence leading to stereodefined r-conjugated alkene derivatives, have been successfully developed in the last decade (4). Alkenylsilanes or siloxanes, prepared via platinum or rhodium complex-catalyzed intermolecular hydrosilylation of terminal alkynes have been highly stereospecifically cross-coupled with aryl and alkenyl halides to give unsymmetrical stilbenes, alkenylbenzenes, and conjugated dienes (Scheme 24) (4). 

Based on these precedents for C—X bond formation between C=N and alkene intermediates (derived from alkynes), the Larock group developed the first transition-metal-mediated pyridine ring formation by direct reaction between C=N and alkynes. Using terminal alkynes 11, rcrt-butylimines 10 were subjected to Sonogashira coupling followed by Cu(I)-catalyzed annulation to afford isoquinolines or pyridines 12 in moderate to good yields (46 to 95%, Scheme 19.5) [5]. A variety of terminal alkynes and aryl/alkenyl halides can be used in the reaction. The stepwise reaction also worked well to form the same products. Similarly, p- and y -carbolines were synthesized effectively, as shown in Scheme 19.6 [6]. 

The reaction of heterocyclic lithium derivatives with organic halides to form a C-C bond has been discussed in Section 3.3.3.8.2. This cannot, however, be extended to aryl, alkenyl or heteroaryl halides in which the halogen is attached to an sp2 carbon. Such cross-coupling can be successfully achieved by nickel or palladium-catalyzed reaction of the unsaturated organohalide with a suitable heterocyclic metal derivative. The metal is usually zinc, magnesium, boron or tin occasionally lithium, mercury, copper, and silicon derivatives of thiophene have also found application in such reactions. In addition to this type, the Pd-catalyzed reaction of halogenated heterocycles with suitable alkenes and alkynes, usually referred to as the Heck reaction, is also discussed in this section. 

When the carbopalladation of the bicyclopropylidene is performed in the presence of methyl acrylate, the reaction takes a different course (Scheme 8.34) [79]. The 1,3-diene intermediate 75 reacts in situ with the dienophile to give the spiro[2.5]octane derivative 76. An extension of this cascade Heck-Diels-Alder reaction involving l,3-dicyclopropyl-l,2-propadiene as the alkene partner, an alkenyl or aryl halide and a dienophile has been reported [80]. 

Primary alkylboranes derived by hydroboration of terminal alkenes with 9-BBN-H are coupled with aryl and alkenyl triflates and halides under properly selected conditions. The reaction proceeds smoothly without elimination of /1-hydrogen using PdCTklppf) or Pd(Ph3P)4 and K3PO4 in dioxane or DMF [132]. The intramolecular cross-coupling of the alkenyl triflate with the alkylborane in 292, prepared by in situ hydroboration of the double bond in 291 with 9-BBN-H, is applied to the annulation to... 

Potential difference in reactivity between two G-B bonds allowed the transformation of l,2-bis(boryl)-l-alkenes to 1-alkenylboranes via a cross-coupling with the aryl, 1-alkenyl, benzyl, and cinnamyl halides (Equation (23)).211-213 This tandem procedure synthetically equivalent to a yy/z-carboboration of alkynes was used for synthesizing Tamoxifen derivatives via stepwise double coupling with two of the G-B bonds.212,213 Hydrogenation of the resulting bisborylalk-enes with a chiral rhodium catalyst is synthetically equivalent to an asymmetric diboration of alkenes (Equation (24)).214... 

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