Propargylated furanones

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. 

Tertiary propargylic alcohols reacted with carbon monoxide in the presence of a cationic palladium(II) complex, [Pd(NCMe)2(PPh3)2](BF4)2, to afford mixtures of 2(5H)-furanones and 2,3-dienoic acids (Scheme 3.23). Control experiments demonstrated that the latter products were converted into the former quantitatively with a trace amount of acid [58],... 

Cyclohydrocarbonylation of 3-TMS-propargyl alcohols cleanly gives the corresponding 2(5//)-furanones. For instance, the reaction of 102 catalyzed by Rh4(CO)i2 yielded spirobicyclic furanone 103 almost exclusively in 97% yield (Equation (4)). " ... 

For the synthesis of furanones, Kirsch et al. studied the gold-catalyzed hetero-cyclization/1,2-migration cascade reaction of a-hydroxy propargyl ketones [139]. 

Terminal and internal propargylic alcohols 73 are carbonylated using DPPB under CO-H2 pressure, and 2(5H)-furanones 75 are obtained via the lactonization of 2,3-dienecarboxylic acids 74. Hydrogen pressure is claimed to be essential [17]. 

Propargyl alcohol was first monoaminocarbonylated leading to 4-hydroxy-2-ynamide 111. This first stage is followed in situ by conjugate addition of dialkylamine to the triple bond of the ynamide to yield 112 which gives spontaneously an intramolecular lactonization to afford the furanone 113. Similarly, lactams have been prepared using propargyl amines [99]. 

Optically active aliphatic propargylic alcohols are converted to corticoids (90% ee) via biomimetic polyene cyclization, and to 5-octyl-2(5ii)-furanone. The ee s of propargylic alcohols obtained by this method are comparable with those of the enantioselective reduction of alkynyl ketones with metal hydrides, catalytic enantioselective alkylation of alkynyl aldehydes with dialkyIzincs using a chiral catalyst ((S)-Diphenyl(l-methylpyrrolidin-2-yl)methanol) (DPMPM), and the enantioselective alkynylation of aldehydes with alkynylzinc reagents using A(A-dialkylnorephedrines. °... 

Propargyl alcohols are less reactive than their esters. Carbonylation of the tertiary propargyl alcohol 68 at 95 °C under pressure of CO and H2 and neutral conditions using DPPB provided the 2(5//)-furanone 69. It was claimed that H2 was required for this reaction [16]. 

In 2006, the group of Artok showed that 5-aryl-2(5H)-furanones could be prepared in moderate to good yields by a rhodium-catalyzed carbonylative arylation of internal alkynes with aryl boronic acids (Scheme 1.9a) [22]. a,P-Unsaturated ketones (chal-cone derivatives) were formed as the major product when some TFA (trifluoroacetic acid) was added under the same reaction conditions [23a]. By varying the catalytic system, indanones could be produced as the main product [23b]. The chemical behavior of terminal alkynes is different, and either a,P-unsaturated ketones or furans starting from propargylic alcohols can be achieved (Scheme 1.9b) [24, 25]. In the case of vinyl ketones, 1,4-diketones were obtained by rhodium-catalyzed coupling of arylboronic acids in the presence of 20-40 bar of CO [26]. In 2007, Chatani demonstrated that indenones could be accessed by a carbonylative rhodium-catalyzed cyclization of alkynes with 2-bromophenylboronic adds (Scheme 1.9c) [27]. Here, the key intermediate is a vinylrhodium(I) spedes that is formed by transmetaUation of RhCl with 2-bromophenylboronic acid followed by insertion of... 

Soon afterwards, the same group developed methodologies for the oxidative carbonylation of 4-yn-l-ones and propargylic esters (Scheme 8.22). While 2-cyclopentenone carboxylates were obtained from appropriate carbonyl-substituted alkynes [96], cyclic orthoesters and furanones were successfully synthesized starting from corresponding propargylic compounds [97]. More recently, they also realized the asymmetric version of this reaction [98], which has also been applied in the total synthesis of (—)-AL-2 by Mukai and Miyakoshi [99]. 

Treatment of 4-pentynoic acids with propargyl acetates in the presence of palladium diacetate, tri(2-furyl)phosphine and potassium carbonate in DMSO affords 5- E)- 2-allenylidene)-tetrahydro-2-furanones (Scheme 30). Employment of potassium carboxy-lates generated by the reaction of 4-pentynoic acids with KOBu-t produces lower yields. 

A Pd-catalyzed carbonylative coupling reaction of propargyl alcohols and thiols has been developed by using different reaction conditions. Monothioesters, dithioesters, or sulfur-containing furanones can be produced in good to excellent yield and selectivity. This methodology is attractive for the preparation of thioesters and sulfur-substituted... 

Alternatively, 5-allyl-2(5/f)-furanones can be obtained from TMSOF and allylic acetates using lithium perchlorate in ether. 5-Propargyl-2(5//)-furanones are prepared by coupling with bex-acarbonyldicobalt complexes of propargylium cations (eq 5). Reaction of the intermediate complex with cerium(TV) ammonium nitrate removes the cobalt Fluoroalkylation is acbieved by using bis(fluoroalkanoyl) peroxides in 1,1,2-tricbloro-1,2,2-trifluoroethane (Freon 113) (eq 6). This process is believed to involve combination of a fluoroalkyl radical with the furan-derived radical cation. 

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