Ketene trapping, intramolecular

Recently, Boeckman and Pruitt [58] demonstrated the use of dioxolenones as precursors of P-acyl ketenes, which can be thermally generated under mild neutral conditions in the absence of other nucleophiles and trapped intramolecularly by the hydroxy group to afford good yields of macrocyclic lactones. The 16-membered macrolide (—)-kromycin 102) has been synthesized in this way by thermolysis of the P-acyl ketene precursor 101 in toluene at high dilution (0.0001 M) in 70% yield (Scheme 34). 

The reaction proceeds through a vinylketene (54) formed via a vinylcarbene (53) the product of ring-opening of the cyclopropene ring. Then, the ketene undergoes intramolecular cycloaddition in benzene or is trapped by methanol (equation 35) °. 

The intramolecular insertion into the N—H bond of j8-lactams was used successfully in the synthesis of bicyclic ring systems. Photochemical, in contrast to Rh(II)-catalyzed, decomposition of diazo ester 62 was found to occur far less selectively. In the photolytic reaction, the imide 63 is the major product. It presumably arises by a photolytic Wolff rearrangement to a ketene intermediate, which is trapped intramolecularly. With Rh2(AcO)4 catalyst the Wolff rearrangement is suppressed and 62 undergoes ring closure to 64 nearly quantitatively (80TL31). 

Barrett s group [59b] exploited the intramolecular ketene trapping-transaimular aromatization sequence firstly developed for (S)-zearalenone (Scheme 7.5) to prepare LL-Z1640-2 starting from 2-deoxy-D-ribose. Thomas and collaborators... 

SCHEME 53. Microwave-assisted diastereoselective synthesis of a a-spiro-8-lactone via a WoUf rearrangement/a-oxo ketene trapping/cross-metathesis/intramolecular Michael addition consecutive sequence. 

A variety of a-spirolactones and lactams from 2-diazo-l,3-dicarbonyl compounds, (homo)allylic alcohols or amines and acrylic derivatives, in a single synthetic operation by a Wolff rearrangement/a-oxo ketene trapping/cross metathesis/ intramolecular Michael addition sequence has been obtained by Boddaert et al. (2011). 

Claisen rearrangement. As for the mechanism, the reaction begins with intramolecular cyclopropanation the resulting bicyclo[2.1.0]pentan-2-one then undergoes fragmentation to a p,y-unsaturated ketene which finally is trapped by the added alcohol to afford a p,y-unsaturated ester (Scheme 41). The intermediates could be observed in selected cases. 

A reasonable mechanism for their formation starts with the primary adduct 339, which is capable of ring-opening to the ketene 340 this can either be trapped by addition of water (337) or undergo intramolecular acylation followed by dehydrogenation (338). 

With 0,-y-unsaturated a -diazo ketones, the resulting [2.1.0]-bicyclic systems (40) were quite unstable and underwent a [2 + 2] cycloreversion to generate ketenes (41), which were then trapped by nucleophiles (Scheme 7). The overall scheme has been named a vinylogous Wolff rearrangement and offers a novel entry to products usually derived from a Claisen rearrangement.102 A recent report describes its application for functionalized angular alkylation in fused ring systems.103 In contrast, the intramolecular re-... 

An intermediate epoxy ketene (39) from a-cleavage of 2,5-diphenyl-3(2H)-furanone (40) has been proposed by Padwa and co-workers to explain photoisomerization to 4,5-diphenyl-2(5H)-furanone (47)38. The epoxy ketene was not observed when the irradiation was monitored by infrared spectroscopy and was not trapped by methanol. The authors suggest that the intermediate may be formed with excess vibrational energy and as a result undergo very rapid intramolecular reaction. 

Intramolecular insertion of carbon monoxide into the metal-carbene bond of the (Ej-isomer of D leads to the t/4-vinyl ketene complex intermediate E. Experimental support for this type of intermediate has been provided by the isolation of Cr( CO) 3-coordinated dienyl ketenes related to 5 (Scheme 4) [15a], and by trapping the vinyl ketene intermediates as vinyl lactone derivatives in the course of the reaction of chromium carbene complexes with 1-alkynols [15b]. 

Intramolecular disproportionation of [1] could conceivably result in the formation of unsaturated aldehyde or ester. Both paths are well known to occur with cyclic alkanones (la). Abstraction of H by the acyl radical portion of [1] would produce alkenal [3] while abstraction of by the alkyl radical portion of [1] would produce ketene [4] which may be efficiently trapped in nucleophilic alcoholic solvents to yield ester [5]. The intramolecular nature of alkenal formation is supported by deuterium labeling experiments (5), while the intramolecular nature of ketene formation is supported by (a) deuterium labeling experiments (6,7), and (b) the observed decrease in ketene formation with decreasing ring size (8). 

An interesting route to a-carboxy-8-lactones (81) and a-methylenelactones (80), based on hydrolysis of Knoevenagel products (79) of Meldrum s acid with cyclic aliphatic ketones (78), has been developed (Scheme 14). Reduction of 5-methylene derivatives of Meldrum s acid has been performed catalyti-caiiyi30 or by use of LAH. Imidoylation reaction of Meldrum s acid and subsequent solvolysis of the resulting (82) yields -enamino esters (83) in good yields.Flash vacuum pyrolysis of alkylidene derivatives of Meldrum s acid can be used to prepare methylene ketenes (84), a class of compounds difficult to prepare by conventional methods. By this procedure, methylene ketenes are obtained from aromatic aldehydes and ketones and from aliphatic ketones in only two steps. Intramolecular trapping of the methylene ketene obtained from the ketone (85) has been used successfully in the synthesis of the naphthol (86). ... 

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