Michael Dieckmann domino reaction

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

The synthesis of these compounds using a domino Michael/Dieckmann process has been developed by Tatsuta [58], Muller [59], and Mori [60]. The reaction schemes are shown in Scheme 2.29. 

Besides the Michael addition-initiated domino reactions presented here, a multitude of other anionic domino reactions exist. Many of these take advantage of an incipient SN-type reaction (for a discussion, see above). In addition to the presented SN/Michael transformations [97, 98, 100], a SN/retro-Dieckmann condensation was described by Rodriguez and coworkers, which can be used for the construction of substituted cycloheptanes as well as octanes [123]. Various twofold SN-type domino... 

Scheme 7.46 Domino Michael/aldol/retro-Dieckmann (MARDi) reaction.

Reagent-based and substrate-based approaches can also be combined in a single two-directional synthesis in which different symmetrical substrates can be used under different reaction conditions to achieve predictable scaffold diversity [23]. In an example by Spring et al, two domino reactions were used to synthesize polycyclic alkaloids from a common substrate 147. A Boc-removal/bicyclization process using AlClj as Lewis acid from 147 was used to produce 5-5, 5-6, and 6-6 bicyclic compounds (148-153), and a domino Michael addition/Dieckmann process/Michael addition reaction yielded 6-6-6, 6-6-5 tricyclic compounds (154-156). The 6-5-5 tricyclic scaffold 156 could not be synthesized by means of the same domino... 

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]. 

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. 

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