Alkynols cyclocarbonylation

Scheme 9.25 Possible mechanism for Pd-catalyzed alkynol cyclocarbonylation.

In 1991, El-Ali and Alper reported the cyclocarbonylation reaction of terminal propargyl alcohols with formation of 5,5-disubstituted 2(5//)-furanones using Pd(dba)2 and l,4-bis(diphenylphosphino)butane (dppb) (91JOC4099). However, this reaction was not applicable to internal alkynols. 

Substituted propargylic alcohols were found to undergo direct carbonylation to the corresponding butenolides in 67-98% yield (Eq. 9.120) [86]. This reaction requires a catalytic amount of Pd2(dba)3-CHC13 (4%) and l,4-bis(diphenylphosphi-no)butane (8%) in CH2C12 under an atmosphere of CO (600 psi) and H2 (200 psi) at 95 °C for 36 h. The cyclocarbonylation reaction is believed to proceed via an allenyl-palladium intermediate, which is formed by initial insertion of Pd(0) into the C-O bond of the alkynol followed by rearrangement (Scheme 9.25). 

Additionally, when Pd-catalyzed cyclocarbonylation of alkynols is carried out in the presence of a large excess of CuCl2 (5 equivalents), (Z)-a-chloroalkylidene-/Mactones are obtained as depicted in Scheme 26 [146,147]. As previously mentioned concerning the intermolecular alkoxycarbonyla-... 

A review on ynolates, including the synthesis of p-lactones, has appeared <03S2275>. Morita-Baylis-Hillman-type adducts have been converted into a-alkylidene-p-lactones 65, which on reaction with dimethyltitanocene can be transformed into 3-alkylidene-2-methyleneoxetanes <03OL399>. Lactones 66 have been obtained via the cinchona alkaloid-catalyzed dimerization of monosubstituted ketenes <03OL4745>. The PdCh-promoted synthesis of P-lactones 67 have been achieved via cyclocarbonylation of 2-alkynols <03OL4429>. 

Pd-catalyzed carbonylation of unsaturated substrates incorporating a nucleophilic function in a suitable position may result in ring formation with CO incorporation into the ring (cyclocar-bonylation). In the absence of external nucleophiles, the cyclocarbonylation process usually results in intramolecular hydroalkoxycarbonylation of the unsaturated bond, both exo and endo cychzation modes being possible, as shown in Scheme 10 for a generic alkynol. 

The reaction of alkenols and alkynols with carbon monoxide in the absence of external nucleophiles results in additive cyclocarbonylation and has been employed for... 

Oxidative cyclocarbonylation-alkoxycarbonylation is usually observed when the reaction of alkenols and alkynols is carried out in the presence of external nucleophiles such as alcohols. /3-Lactones and /3-lactams bearing an exocyclic (Z)-(alkoxycar-bonyl)methylene moiety can be prepared according to a very simple oxidative technique starting from propynyl alcohols or amines. Geminal groups have been found to exert a powerful effect on cyclization. 

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