1- Alkenyl bromides

Other macrocyclic ligands 218 with a single pendant arm have been prepared from l,4,7-triazacyclio[5.2.1.04 10]-decane 40 <1996ICA(246)343> by reacting with appropriate alkyl bromide/alkenyl bromide followed by base hydrolysis (Scheme 34). 

A range of polycyclic benzo b furans illustrated below was formed by the CuI/TMEDA mediated coupling reaction of conjugated aryl bromide-alkenyl triflates <07TL7578>, and a similar reaction was also found in the synthesis of 5-phenyl morphans <07H(71)881>. 

Alkenyl bromides. Alkenyl boronic acids are easily converted by NBS to the corresponding bromides at room temperature (13 examples, 62-86%). 

PdlMeCNljClj] Aryl bromides, alkenyl triflates Air stable, soluble form ofPdClj [73, 74]... 

Arenecarboxylic acids Aryl iodides, triflates Aryl bromides Alkenyl- and allylsilanes Cyclic alkenes Allyl alcohols... 

Finally (d + aV dditions of 1-alkenyl and 1-alkynyl anions to carbonyl groups should be mentioned. Examples are the addition of vinylmagnesium bromide to ketones e.g. in the first step of Torgov s steroid synthesis (I.N. Nazarov, 1957), and the famous alkynylation of... 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

A mixture of E and Z forms is obtained by the reaction of the fZ)-alkenyl bromide 33. Z to E isomerization takes place. However, the reaction is remarkably accelerated by using K2CO3 instead of KHC03[17] and BU4NCI in DMF, and the reaction of the (Z)-iodide 34 proceeds rapidly at room temperature without isomerization[37]. 

Numerous applications have been reported. A derivative of the (alkyn-1-yl)nucleosides 295. which have anticancer and antiviral activities, has been synthesized by this reaction. They are also used as chain-terminating nucleosides for DN.A. sequencing[l98,199]. In this reaction, use of DMF as the solvent is most important for successful operation[200]. Only the alkenyl bromide moiety in 2-bromo-3-aceto.xycycloheptene (296) reacts with alkynes without attacking the allylic acetate moiety[201]. 

The coupling reaction has widespread use in the construction of enediyne systems present in naturally occurring anticancer antibiotics[234]. The Pd-Cul catalyzed coupling reaction of the alkenyl bromides 323 and 326 with the... 

The novel intramolecular reaction of the alkenyl bromide with the terminal alkyne in 328, followed by intramolecular Diels-Alder reaction, afforded the highly strained dynemicin A structure 329 in one stepf237]. 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

Interesting formation of the fulvene 422 takes place by the reaction of the alkenyl bromide 421 with a disubstituted alkyne[288]. The indenone 425 is prepared by the reaction of o-iodobenzaldehyde (423) with internal alkyne. The intermediate 424 is formed by oxidative addition of the C—H bond of the aldehyde and its reductive elimination affords the enone 425(289,290]. 

The o-keto ester 513 is formed from a bulky secondary alcohol using tricy-clohexylphosphine or triarylphosphine, but the selectivity is low[367-369]. Alkenyl bromides are less reactive than aryl halides for double carbonyla-tion[367], a-Keto amides are obtained from aryl and alkenyl bromides, but a-keto esters are not obtained by their carbonylation in alcohol[370]. A mechanism for the double carbonylation was proposed[371,372],... 

The Li compound 588 formed by the ort/io-lithiation of A. A -dimethylaniline reacts with vinyl bromide to give the styrene derivative 589(433]. The 2-phe-nylindole 591 is formed by the coupling of l-methyl-2-indolylmagnesium formed in situ from the indolyllithium 590 and MgBr2, with iodobenzene using dppb[434]. 2-Furyl- and 2-thienyllithium in the presence of MgBr2 react with alkenyl halides[435]. The arylallenes 592 and 1,2,4-alkatrienes are prepared by the coupling reaction of the allenyllithium with aryl or alkenyl halides[436]. 

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Aryl sulfides are prepared by the reaction of aryl halides with thiols and thiophenol in DMSO[675,676] or by the use of phase-transfer catalysis[677]. The alkenyl sulfide 803 is obtained by the reaction of lithium phenyl sulfide (802) with an alkenyl bromide[678]. 

The allylstannane 474 is prepared by the reaction of allylic acetates or phosphates with tributyltin chloride and Sml2[286,308] or electroreduction[309]. Bu-iSnAlEt2 prepared in situ is used for the preparation of the allylstannane 475. These reactions correspond to inversion of an allyl cation to an allyl anion[3l0. 311], The reaction has been applied to the reductive cyclization of the alkenyl bromide in 476 with the allylic acetate to yield 477[312]. Intramolecular coupling of the allylic acetate in 478 with aryl bromide proceeds using BuiSnAlEti (479) by in situ formation of the allylstannane 480 and its reaction with the aryl bromide via transmetallation. (Another mechanistic possibility is the formation of an arylstannane and its coupling with allylic... 

Simple alkyl and alkenyl ethers of pentaerythritol are produced on direct reaction of the polyol and the requited alkyl or alkenyl chloride in the presence of quaternary alkylamine bromide (44). AHyl chloride produces the pentaerythritol tetraHyl ether [1471 -18-7],... 

Organolithium reagents (Section 14.3) Lithium metal reacts with organic halides to produce organolithium compounds. The organic halide may be alkyl, alkenyl, or aryl. Iodides react most and fluorides least readily bromides are used most often. Suitable solvents include hexane, diethyl ether, and tetrahy-drofuran. 

With potassium /m-butoxide in tetrahydrofuran, the dibromodihydro-3//-l-benzazepines 7 (R1 = H, F, Cl) undergo syn dehydrobromination to synthetically useful alkenyl bromides, e.g. 8 (R1 = Cl), accompanied by small amounts of debrominated materials, e.g, 9 (R1 = Cl), and the 3-fcrf-butyl ethers, e.g. 10b(R1 = Cl, R2 = -Bu).78 In contrast, with sodium hydroxide, or with sodium methoxide in dioxane/methanol, the yields of bromo compounds 8 decrease, and significant amounts of the methyl ethers, e.g. 10a (R1 = Cl R2 = Me), arc produced. A mechanistic rationale for these reactions has been offered. 

---