Double cyclization carbonylation

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

The presence of strongly electron-withdrawing substituents, such as the nitro group, inhibits cycliza-tion when positioned ortho or para, but, remarkably, the presence of a carbonyl group has less influence and double cyclizations of dicarboxylic acids are not uncommon, as exemplified in equation (6). 

Benzoyl-l-phenyl-5-methoxycarbonyl-2,3-dihydro-pyrrole-2,3-dione was reacted with 5/5-dimethyl-3-p-methoxyphenylamino-2-cyclohexen-l-one in boiling benzene to afford 6,6-d imethyl-1 -p-methoxyphenyl-2,4-dioxo-2,3,4,5,6,7-hexahydro-lH-indole-3-spiro-2-(3-benzoyl-5-oxo-4-phenyl-amino-2,5-dihydrofuran) in high yield. The reaction proceeded by the enamine addition to the 2-carbonyl group with ring opening, followed by double cyclization (06RJOC772). 

On the other hand, the triflate 254 was treated with sodium azide, followed by reduction of the lactone carbonyl function, and subsequent mesylation, complete removal of the protecting groups and reprotection by EtsSiCl, to afford 259 (Scheme 25). Sodium hydrogen telluride reduction of the azide function in 259 followed by intramolecular double cyclization with sodium acetate afforded the bicycle 260, which on deprotection furnished 261 in 45% overall yield from the triflate 254. 

Another interesting double cyclization process was reported to occur from the carbonylation of o-bis(l-hydroxy-2-propynyl)benzene in the presence of complex [Pd(tu)4]l2 (tu = thiourea) at 25 °C and 30 atm of CO, with selective formation of a naph-thofuranoneacetic ester (Scheme 26). In this case, the process may be viewed as a combination of oxidative dialkoxycarbonylation and reduction of one of the hydroxyl group, the net result being additive dicarbonylation. 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

Allyl methylcarbonate reacts with norbornene following a ruthenium-catalyzed carbonylative cyclization under carbon monoxide pressure to give cyclopentenone derivatives 12 (Scheme 4).32 Catalyst loading, amine and CO pressure have been optimized to give the cyclopentenone compound in 80% yield and a total control of the stereoselectivity (exo 100%). Aromatic or bidentate amines inhibit the reaction certainly by a too strong interaction with ruthenium. A plausible mechanism is proposed. Stereoselective CM-carboruthenation of norbornene with allyl-ruthenium complex 13 followed by carbon monoxide insertion generates an acylruthenium intermediate 15. Intramolecular carboruthenation and /3-hydride elimination of 16 afford the -olefin 17. Isomerization of the double bond under experimental conditions allows formation of the cyclopentenone derivative 12. 

Reinstallation of the fractured spiro ring can be accomplished either directly at the enone level or, more interestingly, after the ketone carbonyl has been capped as in 36. When 36 and stereoisomers thereof are individually subjected to intramolecular oxymercuration, the stereochemical course of the cyclization is dictated by the approach of Hg2+ to that surface of the double bond where coordination to a proximal axially oriented ether oxygen can operate. [31] Where 37 and 40 are concerned,... 

In the latter compounds, the cross-conjugated dienone is replaced by a fu-ran ring conjugated to an E double bond. Biosynthetically, it is not known if these compounds arise from 1,4-dione precursors such as 138 by a Paal-Knorr type cyclization (Scheme 2) or from the a-angelica lactones 134 by reduction of the lactone carbonyl followed by loss of water. 

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