Palladium catalyzed cyclocarbonylation

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

These results were obtained by performing the reactions in slightly different conditions than those used by Torii and coworkers. For instance, they reported the palladium-catalyzed cyclocarbonylation of allyl phosphate with imines in a stereoselective manner, depending on the imine used for the coupling, (Scheme 66), but they could not obtain any reaction product starting from allyl halides [161]. 

Scheme 66 Palladium-catalyzed cyclocarbonylation of allyl phosphate with imines...

C-3 of the naphthalene nucleus that controls the electrophilic ring-closure of the vinyl ketene intermediate moreover, the degree of aromaticity of the angular rings in the phenanthrene skeleton exceeds that in the anthracene analogues. This regioselectivity observed in the benzannulation of chromium carbenes is paralleled by results observed for 2-naphthyl cyclo-butenones [77] and for the palladium-catalyzed cyclocarbonylation of 2-naphthyl allyl acetates [78]. 

The palladium-catalyzed cyclocarbonylation reaction of o-iodoanilines with allenes and CO in l-butyl-3-methylimidazolium hexafluorophosphate [bmimJPFg afforded 3-methylene-2,3-dihydro-lH-quinolin-4-ones in yields of up to 90% under a low pressure (5 atm) of CO (Scheme 17.2). The ionic liquid, as the solvent and promoter, enhanced the efficiency of the cyclocarbonylation reaction. In this work. Ye and group demonstrated the recyclability of the system of ionic liquids and their use as catalysts [44]. 

A similar palladium-catalyzed cyclocarbonylation reaction with norbornene and norbornadi-ene gives products of cis-exo attack with an E configuration at the exocyclic double bond, independent of the stereochemistry of the starting allylic compound52. 

Palladium-catalyzed cyclocarbonylation of 3-(2-thienyl)allyl acetate (632) and 3-(3-thienyl)allyl acetate (634) produces acetoxybenzothiophenes (633) and (635), respectively, in good yields (Equations (115) and (116)) <89TL95>. 

Since Watanabe s synthesis of 4(3H)-quinazolinones in 1993 via transition-metal catalyzed reductive N-heterocychzation [ 181 ], several catalytic methods for quinazoline synthesis have been developed [182-186]. For example, palladium-catalyzed cyclocarbonylations of halides with appropriate reactants provided regioselective synthesis of 4(3H)-quinazolinone derivatives [182] and indoloquinazolines [184]. Also selenium-catalyzed reductive N-heterocyclization to quinazolinones has been developed by Sonoda et al. [183]. Copper-catalyzed heteroannulation with alkynes has been developed as highly region- and stereoselective route to 2-(2-arylvinyl)-l,2,3,4-tetrahydroquinazolin-4-ones 64 by Kimdu et al. [ 185] (Scheme 12). Recently, condensation of anthranylamide with various aldehydes to 4-quinazotinones has been found to give excellent yields in the presence of cupric chloride [186]. 

Quinazolinones are an important class of fused heterocycles that have been reported with remarkable activities in biology and pharmacology such as anticancer, antiinflammatory, anticonvulsant, antibacterial, antidiabetic, hypolipidemic, and protein tyrosine kinase inhibitors. Alper and Zheng reported a palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in 2008. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields (Scheme 3.27a). The reaction is believed to proceed via in situ formation of an amidine, followed by oxidative addition, CO insertion, and intramolecular cyclization to give the substituted quinazolin-4(3H)-ones. Later on, a procedure was established based on generating the amidine in situ by a copper-catalyzed reaction of terminal allq nes, sulfonyl azide and o-iodo-anilines. The desired quinazolinones can be produced by carbonylation with Pd(OAc)2-DPPB-NEt3-THF as the reaction system. In the same year, Alper s group developed a procedure for 2,3-dihydro-4(lH)-quinazolinone preparation. The reaction started with the reaction of 2-iodoanilines and N-toluenesulfonyl aldimines followed by palladium-catalyzed intramolecular... 

BMIPFfiOr BMINTf2 ILs were successfully employed for the palladium-catalyzed cyclocarbonylation of 2-allylphenols or anilines (Scheme 6.11) [93]. High yields of lactones or lactams are obtained with good selectivities. Moreover, the recovered IL catalytic solution can be reused without any significant changes in activity and selectivity. 

Substituted-3-acylindoles have been prepared through the palladium-catalyzed carbonylative cyclization of 2 -alkynyltrifluoroacetanylides with vinyl triflates [102,106]. Analogously, the palladium-catalyzed cyclocarbonylation of bis(o-trifluoroacetamido-phenyl)acetylene 59 with vinyl halides and triflates afforded 12-acyUndolo[l,2-c] quinazoline derivatives in high yields. The palladium-catalyzed reaction of 59 with the vinyl triflates 60 at 50 ° C under 5 bar of carbon monoxide allowed the synthesis of the corresponding quinazoline derivative 61 in 98% yield (Scheme 9.29) [107]. 

In contrast, o-ethynyl-phenols 68 undergo a palladium-catalyzed cyclocarbonylation to afford 3-alkylidene-2-coumaranone 69 (Scheme 9.32). The reaction is envisioned to involve the key intermediate 70. The carbonylpaHadium fragment of 70 adds intra-molecularly to the triple bond. The addition proceeds with syn stereochemistry. The resulting a-vinylpalladium intermediate 71 underlies the reductive elimination of Pd (0) to give the 2-coumaranone derivative and the active catalyst Thermal isomerization of the 7. isomer can occur to some extent under the reaction conditions. 

Some examples in which carbonylative and cychzation steps work separately in a one-pot procedure dealing with the synthesis of oxadiazoles 34 [43,44], quinolines, and naphthyridines 35 [45] have been reported. Oxadiazoles were prepared via palladium-catalyzed cyclocarbonylation of aryliodides or diaryliodonium salts with amidoximes (Scheme 13.16). The acylpalladium complex generated from oxidative addition-insertion reaction between aryliodide/iodonium salt, Pd(0), and carbon monoxide reacts with the amidoxime giving rise, after reductive elimination of Pd(0), to an O-acyl-amidoxime, which in turn undergoes cydodehydratation to oxadiazole in moderate to good yields. 

Larksarp, C. and Alper, H. (1999) Palladium-catalyzed cyclocarbonylation of o-iodophenols and 2-hydroxy-3-iodopyridine with heterocumulenes regioselective synthesis of benzo(e]-l,3-oxazin-4-one and pyrido[3,2-e]-l,3-oxazin-4-one derivatives. The Journal of Organic Chemistry, 64. 9194—9200. 

Allylic halogenides containing an additional internal functional group in a suitable position, e. g., an alkene moiety or a hydroxy group, produce the corresponding cyclopentenone derivatives or lactones, respectively, via palladium-catalyzed carbonylation [43]. Related cyclocarbonylations of cinnamyl halides or acetates to form polycyclic aromatics such as naphthol derivatives have been reported (eq. (15)). Moreover, the synthetic utility of the method was demonstrated by the synthesis of acetoxybenzofurans, acetoxyindoles, and acetoxycarbazoles [44]. 

In a more complicated way, stereospcdfic palladium(II)-catalyzed cyclocarbonylation is achieved with 3-aryl-1-propynes and iodoarenes or acid chlorides, leading to ( >2-arylidenebutenolides S25. This conversion is interpreted as a 1,2-dicarbonylative addition to the corresponding allene. with one of the two newly formed carbonyl groups acting as an ester enolate function. 

Larksarp and Alper used a palladium(II) catalyzed cyclocarbonylation reaction to generate a series of more complex and biologically relevant 4(3 0-Penicillium chrysogenum), have been shown to exhibit PTK inhibition and cholecystokinin inhibition as well as antimicrobial, anti-convulsant, anti-depressant and anti-inflammatory properties. Reaction of o-iodoaniline, a substituted ketenimine, and carbon monoxide with palladium(II) acetate and l,l -bis-diphenylphosphino-ferrocene (dppf) under thermal conditions gave the desired quinazolinone in near quantitative yield. In the same report, the authors showed that similar reactions could also be conducted with isocyanates and carbodiimides (not shown). 

An interesting palladium-catalyzed synthesis of l,2,3,4-tetrahydro-5i/-2-benzazepin-5-ones was developed in 2012 by Alper and Okuro. The reaction proceeded via palladium-catalyzed intermolecular cyclocarbonylation of 2-iodobenzylamines with Michael acceptors. The desired products were isolated in moderate to good yields (Scheme 4.22). This methodology enables the direct preparation of highly functionalized 1,2,3,4-tetrahydro-5H-2-benzazepin-5-ones from readily available starting materials. 

Carbonylation and Related Reactions. The first stereoselective, palladium-catalyzed and reductive cyclocarbonylation of 8,/-substituted allylic alcohols has heen reported. Thus, -allylic alcohols are converted, with high diastereoselectivity, into trans-2,3-disubstituted /-lactones (eq 97). ... 

The reaction of heterocumulenes or alkynes with ortho-iodoanilines under a carbon monoxide atmosphere has been shown to give4(3ff)-quinazolinones or 2-quinolones, respectively. A related cyclocarbonylation reaction has been used to synthesize new cardanol and cardol derivatives in a regioselective manner. Versatile and efficient routes to various spirocyclic compounds, including [5,5]-, [5,6]- and [5,7]-spiroindolines, have been established by exploiting a sequence of palladium-catalyzed cyclization processes (eq 105). ... 

Under oxidative conditions, acyclic [75a,b] and cyclic [75c] 4-yn-l-ols react via a cyclization-methoxycarbonylation pathway to afford ( )-cyclic-P-alkoxyacrylates 2E-[(methoxycarbonyl)methylene]tetrahydrofurans in good yields under mild conditions (Equations 10.37 and 10.38). The stereochemical outcome is entirely consistent with a reaction initiated by intramolecular nucleophilic attack of the hydroxy group on the palladium-coordinated triple bond to generate a vinylpalladiumiodide intermediate that undergoes methoxycarbonylation to afford the P-alkoxyacrylate. The ketopyranose subunit can also be constructed via a palladium-catalyzed oxidative cyclocarbonylation of substituted 5-yn-l-ols, which occurs with excellent stereose-... 

However, cyclocarbonylation of 2-bromo-3,5-dimethoxybenzyl alcohol 22 was successfully achieved by Shimizu and coworkers in the synthesis of mycophenolic acid 23, a fermentation product produced by a number of penicillum species (Scheme 13.11) [34]. The synthesis was carried out using palladium-catalyzed carbonylation and Heck olefination. Thus, the reaction of 2-bromo-3,... 

As an improved alternative to the direct cyclocarbonylation of allylic halides and acetylene derivatives, a two-step procedure has been reported49. Thus, the addition of allylic halides to acetylenic derivatives is catalyzed by palladium(II) complexes, such as bis(acetonitrile)bromo-palladium(ll), followed by cyclocarbonylalion of the resulting cfs-adducts of the alkyne with tetracarbonylnickel in acetonitrile containing precise amounts of methanol and triethylamine. This is a better procedure for the preparation of cyclopentenones than direct cyclocarbonyla-tion mediated by tetracarbonylnickel, especially for monosubstituted or weakly polarized, disubstituted acetylenes. 

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