Negishi E. 2002 Handbook of organopalladium chemistry for organic synthesis / 0335 408

geometry.[57] However, the reaction of benzyl (Z )-3-(tri-n-butylstannyl)propenoate[101] with p-nitrophenyl triflate gives a 2 : 1 mixture of the Z and E isomers of the desired product (Scheme 18). On the other hand, the reaction of (Z )-1-propenyltributyltin and phenyl fluorosulfonate has been reported to produce exclusively (Z )- -methyl-

The use of nitrobenzene as solvent dramatically improves the yields in many cases (Scheme 19).

The Pd-catalyzed cross-coupling reactions of (Z )- -substituted alkenylsilanes with aryl electrophiles, such as aryl bromide,[88] aryl chloride,[83],[88] and aryl triflate,[104] have been demonstrated (Table 4). In these reactions, the presence of either two Si—F bonds or Si—Cl bonds appears to be required for successful coupling, and the addition of bases, such as TBAF and NaOH, is also necessary. In addition, when chloroarenes are used as electrophiles, trialkylphosphines, such as iPr3P, Et3P, and dcpe, must be used as effective ligands. The reaction proceeds with retention of the stereochemistry of the alkenylsilicon derivatives. More recently, a highly stereospecific cross-coupling of alkenylsilanols has been demonstrated,[84] as shown in Scheme 20. The product yields and stereoselectivities are generally high, and the (Z )-alkenyldiisopropylsilanols are superior to the

bromobenzenes fail to react with the reagent under the same conditions.[108] This zincation – cross-coupling procedure (Protocol III) has been used in the synthesis of fluorovinylsalicyclic acid derivatives[109] (Scheme 22). The zinc reagents are often generated by lithiation of the alkenyl halides followed by transmetallation with zinc halides. Some chemoselective and regioselective coupling reactions of alkenylzinc reagents, generated by a lithiation – transmetallation procedure, with o-dihaloarenes have been demonstrated, as shown in Scheme 23.[110]

Scheme 23

Although Markovnikov alkenylboranes have been known since 1975, their Pd-catalyzed cross-coupling had not been reported until an improved procedure for the preparation of Markovnikov alkenylboranes in pure form was recently reported.[115] In these reactions, however, the primary alkyl groups compete with the 2-alkenyl groups and produce alkylbenzenes, but iPr, sBu, and iBu virtually do not. On the other hand, when the alkenylboranes are treated first with 1 equiv of trimethylamine N-oxide, which presumably gives alkenylalkoxyborane,[116] the yields of the desired -substituted styrenes increase dramatically[117] (Scheme 24).

Scheme 24

It is noteworthy that -alkoxy- and -alkylthio-substituted vinylzinc reagents, generated by treating the corresponding organolithium reagents with zinc chloride, undergo Negishi coupling with aryl halides to produce the corresponding arylated -het- erosubstituted alkenes in high yields[118] (Scheme 25). This approach has been demonstrated repeatedly in related Stille and Suzuki coupling reactions (Sect. III.2.13.2).

Scheme 25

-Substituted alkenyltins or alkenylsilicons have not been used as often as their Zn and B counterparts. One problem associated with the use of -phenyl-substituted vinylfluorosilane with aryl iodides is the formation of a mixture of regioisomers. Their ratio depends on the nature of the substituents in the aryl iodides.[18] -Substituted alkenylzirconiums can be prepared by oxidative addition of 2-haloalkenes to zirconocene, and their subsequent Negishi-type coupling with aryl halides has been demonstrated[119] (Scheme 26).

Scheme 26

B.iv. Trisubstituted Alkenylmetals

Some representative examples of the cross-coupling of three different types of trisubstituted alkenylmetals with aryl electrophiles are shown in Table 6 and arranged in the order: , -, cis- , -, and trans- , -substituted alkenylmetals.

(Continued )

B.iv.a. , -Substituted Alkenylmetals. Carbometallation reactions of 1-alkynes, most notably carboalumination[40] and carbocupration,[38] collectively provide a powerful route to the synthesis of , -substituted alkenylmetals. The alkenylmetals generated in situ may be used directly for Pdor Ni-catalyzed cross-coupling with aryl electrophiles (Protocol 1). One prototypical example of the carbometallation–cross-coupling tandem process is shown in Scheme 27.[120]

82%, 99% purity

Scheme 27

In addition to the carbometallation reactions mentioned above, there are various additional methods for the synthesis of trisubstituted alkenes, as discussed below. Various , -substituted alkenylboron compounds can be prepared from 1-alkynes by a haloboration[121]–chemoselective cross-coupling tandem process similar to that shown in Scheme 9. Their subsequent reaction with iodobenzene is effected by the addition of a base to give stereodefined arylated alkenes in fair to good yields.[122] A series of 1,3-dibora-1,3-butadienes have been prepared by a zirconocene-mediated reductive cyclization of 1-alkynyl boronates using Negishi’s reagent[123] (Cp2ZrCl2 2 n-BuLi). Their cross-coupling with aryl halides proceeds to selectively replace the terminal B group giving 2-bora-1,3-butadiene derivatives[124],[125] (Scheme 28). The synthetic utility of this method is severely limited due to the restriction that the two R groups be the same.

R = n-Bu, Ar = Ph (97%), p-MeC6H4 (92%), 2-Thienyl (90%)

Scheme 28

The reaction of 2-bis(trimethylstannyl)-1-alkenes, readily available by the addition of hexamethylditin to 1-alkynes using Pd(PPh3)4 as catalyst,[126],[127] with -chloroarene chromium complexes give regioand stereospecifically the corresponding cross-coupling products in 34 – 85% yields[128] (Scheme 29). On the other hand, uncomplexed haloarenes, such as chlorobenzene or even bromobenzene, fail to undergo the desired cross-coupling. The success with the chromium complexes may be attributable to the electron-withdrawing tricarbonylchromium group, which favors the oxidative addition of aryl chlorides to Pd(0) complexes.[129]

The Pd-catalyzed reaction of (Z )-exocyclic silyldienes[130] with aryl halides has been reported to proceed with some loss of stereochemistry (5–10%)[82] (Table 6).

Cl

R = Ph (70%), MeOCH2 (62%), MeCH(OH) (34%), Me2C(OH) (85%)

Scheme 29

B.iv.b. cis- , -Substituted Alkenylmetals. cis- , -Substituted alkenylmetals containing B, Al, Zr, Sn, and Si can conveniently be prepared via hydrometallation of internal alkynes, and their Pd-catalyzed cross-coupling with aryl electrophiles has been investigated extensively. Some representative results are shown in Table 6. The recently reported Ti-catalyzed hydrozincation that can directly provide stereodefined alkenylzinc reagents[131] from alkynes permits a one-pot Negishi coupling with aryl halides to give arylated alkenes in good yields and in high stereoselectivity. Hydrozincation of unsymmetrically alkyl-substituted alkynes generally produces mixtures of two regioisomers in nearly 1:1 ratios, even though the presence of Ph or an Me3Si group can result in ca. 90:10 regioselectivity. Their cross-coupling with iodobenzene gives mixtures of two regioisomers also in ca. 90:10 ratio[131] (Scheme 30).

Scheme 30

Alternatively, hydrozirconation of 1-alkynyldioxaborolanes with HZrCp2Cl affords 1,1-dimetalloalkenes containing both B and Zr, which can then be reacted with various electrophiles to give trans- , -substituted alkenylboronates via preferential reaction of the carbon – zirconium bond[136] as shown in Scheme 34. The subsequent Suzuki coupling with iodobenzene gives trisubstituted alkenes in good yields.

B.v. Tetrasubstituted Alkenylmetals

Several coupling reactions of 2-substituted cycloalkenylmetal reagents have been re- ported.[139]–[141] For example, cyclobutenylmetals, generated in situ via carbometallation of 4-halo-1-metallo-1-alkynes, are reacted with iodobenzene to give 1,2-disubstituted cyclobutenes,[139] as shown in Scheme 35.