Domino reactions decarboxylative

The first iodine-catalyzed synthesis of 2-alkyl substituted oxazoles 130 by a decarboxylative domino reaction was reported. Aryl methyl ketones 128 were transformed in situ into a-iodo ketones and then, by the Kornblum oxidation, into 1,2-diketones. After the addition of the a-amino acid 129, an l2-mediated cyclization/decarboxylation gave oxazoles 130. The reaction proceeds better if the Ar has electron-donating substituents and if the R group is a branched alkyl chain or phenyl residue. The reaction used oxone to regenerate iodine (13JOC6065). 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

In a similar way, carbocycles having a quaternary center could be obtained from acyclic unsaturated 1,3-dicarbonyl compounds [206]. Other combinations are the domino hydroformylation/Wittig olefmation/hydrogenation described by Breit and coworkers [207]. The same group also developed the useful domino hydroformyla-tion/Knoevenagel/hydrogenation/decarboxylation process (Scheme 6/2.14) [208] a typical example is the reaction of 6/2-66 in the presence of a monoester of malonic acid to give 6/2-67 in 41 % yield in a syn anti-ratio of 96 4. Compounds 6/2-68 and 6/2-69 can be assumed as intermediates. 

The first diastereoselective synthesis of methyl (3R,7R)-jasmonate is attributed to Gerhard Quinkert. [94] In the initial step, starting from bis-(8-phenyhnen-thyl) malonate, a vinylcydopropane is constructed. After removal of the chiral auxiliary, the cyclopentanone is built up by means of a domino homo-Michael reaction / Dieckmann cydisation. Attack of dimethyl pent-2-ynylmalonate leads to inversion at the stereogenic centre at the vinyl cyclopropane. After decarboxylation, the vinyl residue is transformed into an ester group and the triple bond hydrogenated with a Lindlar catalyst. 

An intermolecular approach to carbazoles 273 was reported via an inverse electron-demand Diels-Alder reaction between 3-chloroindoles 271 and pyrones 272. This reaction proceeds through a thermally induced Diels-Alder, decarboxylation, elimination-domino process. Heating the two components under microwave irradiation generates carbazoles with methyl esters in the 3-position in a completely regioselective manner (140L1124). 

A related 1,3-rearrangement, also studied by Jorgensen, is the decarboxylative rearrangement of O-carbamates derived from MBH adducts, an aminereaction that also takes place via a domino Sn2-Sn2 mechanism (Scheme 40.27). 

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