1.2- dihaloalkenes

Still another example is the easy formation of anti-Bredt bicycloalkenones (see p. 188). As indicated above, a,a -dihalophosphoranes can be used to prepare 1,1-dihaloalkenes. Another way to prepare such compounds is to treat the carbonyl compound with a mixture of CX4 (X Cl, Br, or I) and triphenylpho-sphine, either with or without the addition of zinc dust (which allows less Ph3P to be used). " ... 

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). 

It appears that neither the lithium carbenoid pathway nor the cyclopropanation of buta-trienes are general routes to [3]radialenes. More successful is the cyclotrimerization of 1,1-dihaloalkenes via copper or nickel carbenoids, provided the substituents at the other end of the C=C double bond are not too small. Thus, tris(fluoren-9-ylidene)cyclopropane 27 was formed besides butatriene 28 from the (l-bromo-l-alkenyl)cuprate 26 generated in situ from (9-dibromomethylene)fluorene (Scheme 3)10. The cuprate complexes formed... 

The most recent strategy to prepare [3]radialenes is the treatment of 1,1-dihaloalkenes with activated nickel. Thus, the aryl-substituted [3]radialenes (Z,E,E)-30 and (E,E,E) 30, 27 and 32 were obtained together with the corresponding butatrienes (29, 28, 31) from the 1,1-dibromo- or 1,1-dichloroalkenes with the help of nickel activated by ultrasound (Scheme 4)11. It is worth mentioning that the mixed-substituted radialene 33 was produced, when the nickel carbenoid derived from 9-(dichloromethylene)xanthene was generated in the presence of butatriene 2811. 

As shown in Eq. 2.39, 1,1-dihaloalkenes react with zirconacyclopentadienes to afford fulvene compounds (56) [7p]. 

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. 

CeH5)3P + (C6H6)3PCX3X - (C4H5)3P=CX2 + (C6H5)3PX2 1,1 -dihaloalkenes.14 15 17... 

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. 

Trichloroalane in dichloromethane cleaves isopropyl aryl ethers leaving methyl aryl ethers intact. A variety of functional groups (aryl halides, 1,1-dihaloalkenes, aldehydes and acetates) withstand the reaction conditions but alkynes and TIPS ethers do not survive. Scheme 4 110 illustrates an application of the reaction to a synthesis of the Fagaronine alkaloids,201 TVichloroborane in dichloromethane may also be used for the deprotection of isopropyl ethers.202... 

Carbon radical generation. Radicals that are formed during dehalogenation can be intercepted intramolecularly by a C=C bond " or C=N bond. A cyclopen-tene synthesis from 1,1-dihaloalkenes apparently involves two-stage reduction, which is intervened by hydrogen abstraction. 

The other organometallic compounds, such as alkynylcoppers, alkenylzincs, and alkenylzirconocenes, have also been utilized for the tran -selective couphng reaction of 1,1-dihaloalkenes (Scheme 4). The monoalkynylation of 1,1-dichloroethylene in the presence of palladium and copper catalysts is troublesome. Since dialkynylation is not easily suppressed, an excess amount of the substrate, 1,1-dichloroethylene, is required to produce the desired product. 

Selective hydrogenolysis of one of the halogens in 1,1-dihaloalkenes is another possibility to produce disubstimted alkenes in a stereoselective manner. The reaction is achieved by using tributyltin hydride in the presence of Pd(PPh3>4 catalyst (Scheme The catalyst also plays an important role in achieving the selective... 

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... 

The trawi-selective cross-coupling of 1,1-dihaloalkenes exhibiting >98% stereoselectivity has found various interesting and attractive applications in natural products synthesis, as represented by those of lissoclinolide, (-)-chlorothricolide, and kijanolide.t These and other examples are summarized in Table 9. 

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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