Terminal arylation

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

Ionization methods leading to unstabilized cations can give pieparatively useful yields when the center is tertiary. In Scheme 17 a variety of examples is shown. Cyclohexene epoxides (example 2, Scheme 17) are generally useful initiators for monocyclizations. The cyclopropyl ketone is effective with aryl termination (example 4, Scheme 17), but in example 5 (Scheme 17) the ion obtained on cyclization is quenched by intramolecular attack of the enol. 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl... 

Couplings have also been afforded using trimethykilyl derivatives of aryl terminal alkynes of type 3 in one-pot Sonogashira reactions in excellent yields (see Scheme 2) [11]. 

An iV-phenyl-allylamine has been arylated terminally using phosphine-free conditions and a heteroaryl iodide in the synthesis of an H+/K+-ATPase inhibitor (Figure 3.31) [91]. This class of inhibitors has attracted the interest of many medicinal chemistry groups due to the large sales of the blockbuster Losec/Prilosec (Omeprazole). In the cited case, the allylic amine moiety was added at a late stage of the synthesis and the primary amine was protected by Boc to prevent formation of 7r-allyl palladium complexes. The deprotection was then performed with trifluoroacetic acid. 

Functionalization of polythiophenes with aryl groups has attracted much interest because aryl terminals can be further functionalized. A series of 3-phenyl- and 4-phenylthiophene substituted on the phenyl ring with donor or acceptor groups has been electropolymerized [208] in order to tune the potentials for p and n doping. Monomer oxidation potential and polymer redox potentials were found to follow a linear Hammett correlation. 

Siloxy dienes can be converted to bicyclo-[3.2.1]octane derivatives via 2-siloxy-2-alkenyl-l,l-dichlorocyclopropanes synthesized from the former. The dichlorocyclopropanes with aryl-terminated side chains undergo silver-assisted electrocyclic opening to furnish 2-siloxycyclopentenyl cations, which in turn are intercepted by the pendant arenes to furnish the product, that is, by Nazarov cyclization (Scheme 6.44) [49]. 

Domino Heck Reaction with Silane or Aryl Terminator... 

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

The terminal diyne 320 is prepared by coupling of the zinc acetylide 318 with /rfln.s-l-iodo-2-chloroethylenc (319), followed by elimination of HCI with sodium amide[231]. Similarly, terminal di- and triynes are prepared by using cw-l,2-dichloroethylene[232]. The 1-alkenyl or l-aryl-2-(perefluoroalkyl) acetylene 321 is prepared by the reaction of a zinc acetylide with halides[233]. 

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]. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Terminal alkynes undergo the above-mentioned substitution reaction with aryl and alkenyl groups to form arylalkynes and enynes in the presence of Cul as described in Section 1.1.2.1. In addition, the insertion of terminal alkynes also takes place in the absence of Cul, and the alkenylpalladium complex 362 is formed as an intermediate, which cannot terminate by itself and must undergo further reactions such as alkene insertion or anion capture. These reactions of terminal alkynes are also treated in this section. 

Many examples of insertions of internal alkynes are known. Internal alkynes react with aryl halides in the presence of formate to afford the trisubstituted alkenes[271,272]. In the reaction of the terminal alkyne 388 with two molecules of iodobenzene. the first step is the formation of the phenylacetylene 389. Then the internal alkyne bond, thus produced, inserts into the phenyl-Pd bond to give 390. Finally, hydrogenolysis with formic acid yields the trisubstituted alkene 391(273,274], This sequence of reactions is a good preparative method for trisubstituted alkenes from terminal alkynes. 

The carbonylation of aryl iodides in the presence of terminal alkynes affords the acyl alkynes 565. Bidentate ligands such as dppf give good results. When PhjP is used, phenylacetylene is converted into diphenylacetylene as a main product[4l5]. Triflates react similarly to give the alkynyl ketones 566[4I6], In... 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

The terminal amino group of 2-hydrazino-4-phenylthiazole is also the reactive center in reactions with activated aryl halides such as 288. A solution of the product (289) obtained from this reaction when shaken with PbOj gives a deeply colored radical, whose structure has been studied by ESR (Scheme 173) (532. 533). 

Antioxidants markedly retard the rate of autoxidation throughout the useful life of the polymer. Chain-terminating antioxidants have a reactive —NH or —OH functional group and include compounds such as secondary aryl amines or hindered phenols. They function by transfer of hydrogen to free radicals, principally to peroxy radicals. Butylated hydroxytoluene is a widely used example. 

Materials that are comprised of small fragments of (SN) with organic terminal groups, e.g., ArSsNaAr and ArS5N4Ar (Ar = aryl), are of potential interest as molecular wires in the development of nanoscale technology. Consistent with simple band theory, the energy gap... 

Salts of mono-alkylated or arylated sulfur diimide anion [RNSN] (R = aryl, Bu, SiMcs) are prepared by Si-N cleavage of RNSNSiMcs with [(Me2N)3S][Mc3SiF2]. ° ° These anions adopt cis configurations with very short terminal S-N bond lengths (1.44 - 1.49 A) indicative of a thiazylamide anion, [RNS N] (5.21). ... 

Transannular Te N interactions have also been employed to stabilize compounds of the type 15.24 with terminal Te=E (E = S, Se) bonds.The Te=Se bond length in 15.24b is 2.44 A (cf. 2.54 A for a Te-S single bond) and d(Te N) = 2.62 A. Intramolecular coordination was also employed in the isolation of the first aryl-selenenium and -tellurenium cations 15.25a,b as [PEg] salts. 

It was found recently that the cyclization requires the application of 2 moles of alkaline hydroxide in practice, a small excess was used. It was demonstrated that the cyclization is termined wdthin 15 min, and even sooner with a-aryl or 2-A -aIkyl derivatives." ... 

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