Triple bond formation intramolecular cyclization

A plausible mechanism was proposed in Scheme 7.10. Firstly, 2- alkynyl-benzaldehydes 20 could be easily obtained via a Sonogashira reaction of 2-bromobenzaldehyde with alkyne. After condensation with sulfonohydrazide, N -(2-alk50iylbenzylidene)hydrazide I would be afforded. Subsequently, the 6-endo-cyclization would occur to generate the isoquinolinium-2-yl amide II in the presence of suitable Lewis acid. In this step, the formation of a p-complex via coordination of the alkynyl moiety of 20 to the Lewis acid would be involved, thus activating the triple bond for further cyclization. Meanwhile, die in situ formed enolate (derived from ketone or aldehyde in the presence of base) would attack the isoquinolinium-2-yl amide II to produce intermediate III. Subsequent intramolecular condensation and aromatization would give rise to the desired product 22. 

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

Acylpalladium intermediates can be involved in intramolecular processes leading to the formation of carbo- or heterocycles. In this chapter we discuss the cyclizations via the attack of acylpalladium intemediates at carbon centers and formation of new G-G bonds. The basic scheme (Scheme 7) of such processes includes the oxidative addition of Pd(0) to G(j )-X bonds (X = halogen or triflate), migratory insertion of GO, and subsequent intramolecular addition of acylpalladium intermediate to double or triple bonds to yield cyclic ketones. 

The rather unusual precatalyst silver(i) isocyanate was found to efficiently catalyze the cyclization of propargyl carbamates 420 to 4-alkylideneoxazolidin-2-ones 421 in good to high yields (Scheme 123).348 The presence of a base such as potassium /-butoxide or triethylamine is required for formation of the amide nucleophile which undergoes a stereoselective intramolecular attack at the activated triple bond (/rstereo-isomer 421 exclusively. Likewise, homopropargyl carbamates are converted into six-membered (Z)-4-alkylidene-l,3-oxazinane-2-ones under the same conditions. 

A one-pot procedure for the palladium-catalyzed allylation/cyclization of o-alkynyltrifluoroacetanilides 57a [57] and o-alkynylphenols 57b [58] was developed by Cacchi et al. (Scheme 20). This method provides a valuable tool for the synthesis of 2-substituted-3-allylindoles 58a and 2-substituted-3-allylbenzofurans 58b. It was reported that reaction proceeded through the formation of X-allyl derivatives, which form 7r-allylpalladium species 59. A subsequent rearrangement of 59 would then lead to the 7r-allylpalladium species 60. Intramolecular nucleophilic attack of the hetero atom across the activated carbon-carbon triple bond in 60, followed by reductive elimination of Pd(0) gives the products 58. A similar reaction was reported by Balme et al. [59]. 

Nickel(0)-catalyzed hydrosilylation of 1,7-diynes allows intramolecular carbosilylation of one triple bond and formation of bis-alkylidene cyclohexanes with stereoselective formation of a (Z)-vinylsilane subunit60. This reaction resembles reductive cyclization of diynes catalyzed by palladium complexes (see Section 1.5.8.2.6.). 

The carbopalladation is a central reaction in organopalladium chemistry and is extensively presented in Part IV. hi most reactions, a discrete organopalladium intermediate adds to a donble or triple bond. In this section, the reaction of an alkyl iodide with di-ethylzinc in the presence of a palladium(O) catalyst is presented. Such reaction conditions generate an alkyl radical that readily adds intramolecularly to a double bond, leading to an organozinc derivative (Scheme 1). The combination of a radical cyclization with the formation of an organometallic product allows new synthetic applications that will be discnssed. Closely related Ni-catalyzed cyclizations will also be briefly presented. 

As described above, nickel is liable to form Ti-coordination with unsaturated hydrocarbons as shown in Figures 19.3—19.6. By taking advantage of the readiness of these r-coordination formation reactions, oligomerizations such as dimerization and trimerization, cyclizations, polymerizations and coupling reactions of nickel compounds with unsaturated compounds are liable to proceed as shown in eqs. (19.36)-( 19.38). For example, the coupling reaction, coupling cyclization and intramolecular cyclization are shown in eqs. (19.46)-( 19.49). These reactions are considered to proceed via -coordination of unsaturated bonds such as double bonds, tripled bonds and allyl bonds [49,65, 86-91]. 

It is assumed that cyclization proceeds by Cu-promoted intramolecular nucleophilic addition of the imine moiety to the triple bond (77 —78) with loss of the tBu group by formation of isobutene. The imines 77 are accessible from (2-halogeno)benzaldehydes 80 (X = Br, I) by Sonogashira coupling with terminal alkynes and imine formation with (CH3)3C-NH2 or vice versa. 

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