Reactions with 1,1-dihaloalkenes

Ynamines can also be produced by a or jS eliminations in the reaction of dihaloalkenes or trihaloalkenes with alkali metal amides [10,21] (Eqs. 26-29). 

Double Heck reactions of vicinal ci5 -l,2-dihaloalkenes provide an easy access to (E,Z,E)-1,3.5-hexatrienes, which are valuable building blocks for organic synthesis. t t The first example of a twofold double, that is, essentially a fourfold, Heck reaction with a bis(dibromo)cycloalkene has been conducted on the strained l,2,9,10-tetrabromo[2.2] paia-cyclophane-1,9-diene, which is available in multigram quantities. The Heck reaction proceeded cleanly under phase transfer conditions, as developed by Jeffery, f i to give the tetraalkenylated products in moderate to good yields (Table 8). The resulting bishexatrienes... 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

The Pd-catalyzed reaction of alkynylzincs with alkenyl electrophiles is generally dependable and widely applicable. However, recent studies with 1,1-dihalo-l-alkenes, 1,2-dihaloalkenes, and other alkenyl halides have indicated that the presence of two proximal... 

In the above procedures, the preparation of 1,1 -dihaloalkanes is indispensable, but it often contains some synthetic difficulties. Several efficient methods have been reported for their preparations. Halogen-exchange reaction is one of the most commonly used (Scheme 3)20. Selective reduction of 1,1-dihaloalkene with diazene also gives 1,1-dihaloalkane21. 

The olefination of cyclobutanones with the tetrabromomethane/triphenylphosphane reagent (Corey-Fuchs reaction) affords the dihaloalkene in the usual manner.241,242... 

The products formed from the reactions of tellurolates with a,chain length of the dihalide. 

Bis(pinacolato)diboron 8 also reacts with 1-halo-l-lithioalkenes 10 (available from 1,1-dihaloalkenes or 1-haloalkenes by halogen-metal exchange or metalation reaction, respectively) to afford 1,1-bismetalated dienes 11. These are readily converted into polysubstituted dienes through various transition metal-catalyzed carbon-carbon bond formations (Scheme 4) [29]. However, these seemingly attractive methods must not hide the problems of the stereochemistry and regiospecificity of the subsequent cross-coupling reactions. 

The reactions of the /3-halogenovinyliodonium salts 24a,b with halide ions are quite slow, but proceed at 60°C to give a substitution product, (Z)-l,2-dihaloalkene 25, with complete retention of configuration (Scheme 22)." No inverted products were detected. As shown in Fig. 8 the rate of the reaction changes with halide concentration in the same way as for the /3-elimination. That is, the reaction must occur as an intramolecular process of the A -haloiodane intermediate as does the j8-elimination. Another characteristic of the reaction is the formation of the retained iodoalkene 26. The results are best accounted for by the ligand coupling mechanism within the hypervalent iodine intermediate The trends have been explained... 

The coupling reaction of 1,1-dihaloalkenes at the trans position is much faster than that at the cis position because of steric reasons, and therefore, the cis trisubstituted alkenes can be obtained in good yields. In contrast, when a good leaving group is placed at the cis position, the corresponding trisubstimted alkenes having trans stereochemistry can be produced. One typical example is use of (Z)-l-chloro-l-iodoalkenes, which are synthesized by treattnent of ( )-l-chloroalkenes with butyllithium at-100 °C followed... 

Similarly, 1,1-dihaloalkenes are versatile electrophiles that show a remarkable stereoselectivity in cross-coupling reactions. Pd-catalyzed coupHng with alkenylz-incs is trans selective and yields 2-halo-l,3-dienes with excellent stereochemical purity [182-185]. As illustrated with the preparation of 226, PdCljIDPEPhos) is a remarkable catalyst to perform this reaction [186] (Scheme 4.50). The 2-halo-1,3-diene products can then be engaged in a second Negishi cross-coupling reaction that shows a remarkable stereochemical behavior (Scheme 4.50). Typical... 

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