Alkenyl halides, trisubstituted

The stereodefined alkenyl halides are of prime importance due to the recent developments of di- or trisubstituted alkene synthesis by cross-coupling reactions between organometallics and alkenyl halides catalyzed by transition metal compounds 171). These alkenyl halides can be conveniently obtained from alkenylboranes or alkeneboronic acids. B-Alk enylcatecholboranes undergo rapid hydrolysis when stirred with excess water at 25 °C (Eq. 109)102). The alkeneboronic acids are usually crystalline solids of low solubility in water and can be easily isolated and handled in air without significant deterioration. 

Like hydroalumination and hydrozirconation, hydroboration of alkynes also provides a convenient and Stereospecific route to alkenyl metal reagents. However, initial attempts to achieve palladium-catalyzed cross-coupling of alkenylboranes with alkenyl halides were unsuccessful, due to the poor carbanionic character of these reagents. Later, Suzuki discovered that the desired transformation could be effected in the presence of an alkoxide or hydroxide base weaker bases, such as sodium acetate or triethylamine, were not generally effective. The reaction is suitable for the preparation of ( , )-, ( ,Z)- and (Z,Z)-dienes. Since reactions of alkenylboronates are higher yielding than those of alkenylboranes, the recent availability of (Z)-l-alkenylboronates " substantially improves the Suzuki method for the preparation of (Z)-alkenes. An extension of the methodology to the synthesis of trisubstituted alkenes has also been reported. " ... 

Addition of fluoride (as TBAF, the salt Bu4NF) gives the ate complex 210 that couples with aryl and alkenyl halides to give a single isomer of a trisubstituted unsaturated alcohol, e.g. 202, with retention at the alkene. 

The stereodefined alkenyl halides are of prime importance due to the developments of di- or trisubstituted alkene synthesis by cross-coupling reactions between organometallics and alkenyl halides, catalyzed by transition metal compounds [1-4]. 1-Halo-l-alkenes are conveniently synthesized via hydrobo-ration-halogenation reaction [5]. However, with these methods it is not possible to synthesize 2-halo-1-alkenes. Although the halometalation reaction is considered to be a powerful tool for the synthesis of 2-halo-1-alkenes, the reaction has not been adequately developed for such purpose [6]. Lappert and coworkers [7-10] are perhaps the first to report the systematic haloboration reactions of unsaturated hydrocarbons with BX,. However, there is no systematic approach to the haloboration with B-X-9-BBN to organic synthesis [11]. The desired B-X-9-BBN is prepared [12] by the reaction of 9-BBN with phosphorous pentachlo-ride, bromine, or HI. Alternatively, B-X-9-BBN are very conveniently obtained... 

A methodology to access trisubstituted macrocyclic ( )- and (Z)-alkenes from ring-closing metathesis (RCM) has been described. The strategy employs a substrate controlled RCM reaction of linear vinylsiloxanes to generate macrocyclic ( )-alkenyl siloxanes selectively. Conditions were developed to convert the alkenyl siloxane products into alkenyl halides with retention or inversion of configuration of the alkene geometry. 

Haloboration of 1-aIkynes followed by chemoselective cross-coupling can provide j8,/3-substituted alkenylborons that undergo Pd-catalyzed coupling with alkenyl halides to give stereodeflned trisubstituted alkenes. The use of other /3,/3-substituted alkenyl-metals has also been demonstrated. For example, exocyclic alkenylmetals containing Zn and Sn have been nsed in Pd-catalyzed cross-coupling approach to the vitamin D skeleton as shown in Scheme 65. It shonld be noted that the alkenylzinc appeared to be distinctly snperior to the corresponding alkenyltins. 

Vinyl silanes continue to attract attention as intermediates for the stereoselective synthesis of olefins. Zweifel and Lewis now describe the stereoselective synthesis of both -and Z-(l-halogenoalk-l-enyl)silanes (15) from alk-l-ynyl-silanes, and show how they may then be processed to dialkyl-substituted vinyl-silanes, alkenyl halides, and trisubstituted olefins (Scheme 12). The E-l-halogenoalkenyltrimethylsilanes are readily prepared in high isomeric purity by treatment of the dialkylhydroalumination adduct (14) with N-chlorosuccinimide,... 

Scheme 17 -Selective synthesis of trisubstituted alkenyl halides...

Subsequently, the same group reported a more practical method for preparing indoles by using the azaallylic anion as a synthon (Scheme 8) [36]. They found that imines 25 could couple with o-dihalobenzenes 26 to produce intermediates 27, which underwent an intramolecular aryl amination to afford 1,2,3-trisubstituted indoles 28. Because the azaallylic anion could be prepared by a Pd-catalyzed reaction of alkenyl halides and primary amines, they were able to develop a domino three-component synthesis of indoles. 

Coupling Reactions. The palladium-catalysed cross-coupling of E—(1-alkyl-l-alkenyl)boronates with alkyl halides has been shown to permit stereo- and regio-specific access to trisubstituted alkenes in which the introduced alkyl group occupies the position formerly occupied by the boron substituent.201 A1lyl-silanes may be obtained... 

B.iv.c. trans-a,pSubstituted Alkenylmetals. The accessibility of trani-a,/3-substituted alkenyhnetals is still rather limited, and only a few examples of this type of crosscoupling reactions have been reported (Table 6). Notably, trtmi-a,/3-substituted alkenylboronates can be prepared by hydroboration of 1-bromo-l-alkynes followed by subsequent treatments with organolithiums and bases, a procedure similar to that for the preparation of (Z)-/3-substituted alkenylboron compounds.t " Et The Pd-catalyzed crosscoupling reaction of the resultant organoboranes with aryl halides proceeds with complete retention of alkenyl stereochemistry to give trisubstituted alkenesP (Scheme 33). 

Other approaches to trisubstituted aikenes via organoboranes involve alkynyltrialkyl borates, alkenyltrialkyl borates or the cross-coupling reaction of alkenylboronic acids with alkyl halides. Both ( )- and (2)-l,2-disubstituted alkenyl bromides can also be prepared by the methodology shown in eq 7. The boron trifiuoride etherate-mediated 1,4-addition of 1,2-disubstituted alkenylboronates affords y,5-unsaturated ketones (eq 9). The boronates can also be converted into chiral enoiborates for the enantioselective addition to aldehydes. ... 

B.i.b. Alkynes Containing Proximate 1,3-Dicarbonyl Groups. 2-Propargyl-1,3-dicarbonyl compounds react with alkenyl triflates or alkenyl/aryl/heteroaryl halides to give 2,3,5-trisubstituted-furans (Scheme 4). The process probably proceeds through an oxypalladation step that involves a nucleophilic attack of a stabilized enolate across the activated carbon-carbon triple bond, reductive elimination of a palladium(0) species from the resultant oxypalladation adduct, and isomerization of the initially formed alkylidene derivative. 

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