Carbonylative annulation

Thiourea was used as stabilising agent for zerovalent Pd species [117]. The Pd-thiourea (H2NCSNH2) catalysed carbonylation of terminal alkynes and allylic alcohols has been described by Chiusoh [118]. More recently, Pd-thiourea-catalysed carbonylative annulation was studied. The reaction proceeds between alkynes, iodophenol acetates and carbon monoxide, in the presence of dppp, thiourea (H2NCSNH2) and base at 40 °C. Flavones have been obtained in good yields (Scheme 30) [119]. 

The insertion of alkynes into arylpalladium complexes might also be accompanied by the insertion of carbon monoxide into the resulting vinylpalladium intermediate. The carbonylative annulation of TV-protected 2-iodoanilines and internal alkynes under an ambient pressure of carbon monoxide resulted in the formation of 2-quinolones (4.14.), The protection of the nitrogen atom in the aniline is crucial to the success of the reaction. 

A general synthetic methodology and mechanistic details for the palladium-catalyzed carbonylative annulation of the o-alkynylphenol to construct 2-substituted-3-arylcarbonyl-benzo[fo]furans was reported <02JOC2365>. 

The palladium-catalyzed carbonylative annulation of 3-(2-iodophenyl)-benzo[ ]furan 125 provided benzo[/5]-indeno[l,2-4 furan-6-one 126 in 81% yield, as can be seen in Equation (107) <2002JOC5616>. 

The palladium-catalyzed carbonylative annulation of o-hydroxyphenylacetylene was employed to generate methyl benzo[h]furan-3-carboxylate, a key intermediate for the total synthesis of the natural product wedelolactone <03JOC8500>. 

As depicted below, a procedure for the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisole and subsequent direct palladium-catalyzed earbonylatiori/lactonization was reported as an efficient entry to naturally occurring eoumestan and coumestrol <05IOC9985>. A novel Pd(II)-mediated cascade carbonylative annulation of substituted o-hydroxyphenylacetylenes to give benzo[fo]furan-3-carboxylie adds was achieved in a one-pot reaction <050L2707>. 

An efficient synthetic methodology was developed in which the palladium-mediated intramolecular carbonylative annulation of o-alkynylphenols was employed to construct benzo[l>]furo[3,4-d]furan-l-ones by a tandem reaction. Several densely functionalized alkynyl- phenols were cyclized into their respective substituted benzo[fc]furo[3,4-d]furan-l-ones in good yields under conditions of a combination of PdCljfPPh,), dppp and CsOAc in acetonitrile at 55°C under a balloon pressure of CO. An example is depicted below <01OL1387>. 

The reactive double bond, recreated after a chemo- and regioselective a-arylation of enamides, can be further manipulated via a carbonylative annulation, furnishing attractive l-(3-indanonyl)pyrrolidin-2-one structures as exemplified by Wu et al. [67]. In its simplicity, this sequence constitutes an illustrative example of the synthetic versatility of arylated enamides (Figure 3.15). 

Figure 3.15 Synthesis of branched aryl enamides and their use in carbonylative annulations.

In 2000 Yang and Miao reported a novel method for the preparation of flavones [64]. Various flavones are easily synthesized via palladium-catalyzed carbonylative annulation of iodophenol acetates with terminal acetylenes in high yields (Scheme 5.29). This novel reaction provides the possibility of a combinatorial synthesis of flavones on solid supports. 

Hu, Y, Zhang, Y, Yang, Z. and Fathi, R. 2002. Palladium-catalyzed carbonylative annulation of o-alkynylphenols Syntheses of 2-substituted-3-aroyl-benzo[h]furans. J. Org. Ghem. 67 2365-2368. 

Disubstituted coumarins were obtained by a Pd-catalyzed carbonylative annulation of 2-iodophenols with internal aUcynes [40] (without formation of chromones). 

Allenylcyclopropane 51 generated in situ from 3-cyclopropylprop-2-yn-l-yl ester 52 via rhodium-catalyzed 1,3-acyloxy migration underwent carbonylative annulation to give the six-membered ketone 53 (Scheme 2.42) [61]. The [5+1] annulation reaction proceeds via a mechanism analogous to that described for iridium-catalyzed carbonylation of allenylcyclopropanes [62]. 

When the rhodium-catalyzed reaction of bicyclopropyl 56 was performed under latm of CO, carbonylative annulation occurred, producing a seven-membered ketone ring (Scheme 2.45) [65]. 

Carbonylative annulation of cyclopropenes with an alkynyl chain at the sp carbon occurred under CO atmosphere in the presence of a rhodiumfl) catalyst to yield pentasubstituted phenols (Scheme 2.99) [153]. 

Scheme 2.99 Rh(l)-catalyzed carbonylative annulation of cyclopropene-ynes.

A related carbonylative annulation provides 3-(bromomethy-lene)indolin-2-ones stereoselectively (eq 29). ... 

Under the same conditions, o-iodophenol and aniline derivatives also undergo carbonylative annulation with terminal alkynes in the presence of carbon monoxide to form the corresponding coumarins and 2-quinolines, respectively [80]. This is a particularly interesting discovery because analogous palladiumreactions between a terminal alkyne, o-iodophenol, and CO have previously been reported to afford either aurones or chromones, whereas the corresponding reaction with o-iodoanilines generates six-membered ring 4-quinolines. 

More recently, an efficient strategy for these carbonylative annulations has been developed starting from o-iodophenol acetates, instead of o-iodophenols, and terminal acetylenes (Scheme 13.8, path c) [33], The reaction, mediated by a palladium-thiourea complex under a balloon pressure of CO, generates diversified flavones 15 in high yields and in a regiospecific fashion (Scheme 13.9). 

Kadnikov, D.V. and Larock, R.C. (2000) Synthesis of coumarins via palladium-catalyzed carbonylative annulation of internal alkynes by o-iodophenols. Organic Letters, 2, 3643—3646. 

Nan, Y., Miao, H. and Yang, Z. (2000) A new complex of palladium-thiourea and carbon tetrabromide catalyzed carbonylative annulation of o-hydroxylarylacetylenes efficient new synthetic technology for the synthesis of 2,3-disubstituted... 

An important further development came from the group of Yang et al., who reported on a catalytic variant of the carbonylative annulation of benzyl alcohols (Scheme 15.14). The best results were achieved by generating the Pd-complex in situ from the reaction of Pd(OAc)2 with tetramethyl thiourea in the presence of ammonium acetate and propene oxide in tetrahydro-furan. The feasibility of Pd-thiourea as a unique catalyst has been demonstrated in the construction of a fused pyran y-lactones 45 and 46 (Scheme 15.14), the key intermediate in the total syntheses of micrandilactone A" and crisamicin A . 

SCHEME 15.13. Cis-stereoselectivity of Pd-mediated carbonylative annulation of allyl alcohols. 

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