Domino reactions Michael reactions

Scheme 10.4. Domino HWE/Michael reaction under high pressure.

Thus, a domino-Heck-Michael reaction has been reported by Yamada and co-workers [87]. This transformation allowed the formation of three contiguous cycles in one single operation. The mechanism involves first a Heck alkenylation of the iodide 95 which after a /1-hydride elimination step leads to intermediate 96 which undergoes attack of the a-nitro group carbanion to produce the tricyclic compound 97 (Scheme 37). 

Zhong et al. also developed a domino double Michael reaction to access multi-substituted cyclopetanes 20 with excellent enantioselectivities (90-99% ee) and high diastereoselectivities (95 5->99 1) catalyzed by 9-amino-9-deoxyepiquinine lo (Scheme 10.24). A similar concerted activation mode was proposed [32],... 

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. 

Scheme 2.44 Three-component domino Heniy/Michael reaction catalysed by a combination of a chiral preformed nickel catalyst and a microencapsulated amine catalyst.

Scheme 4.34 Multicatalysed three-component domino Henry/Michael reaction.

In the same area, an asymmetric domino double Michael reaction was initiated by this catalyst, providing an expedited access to chiral multi-functionalised live-membered rings. This time, the reaction occurred between a nitroalkene and ethyl 2-acetyl-5-oxohexanoate, yielding the desired double Michael adducts in high yields and excellent diastereo- and enantio-selectivities (Scheme 1.66). An immense potential of synthetic versatility of the... 

The domino Henry-Michael reaction of CH3NO2 with 7-oxo-hept-5-en-l-als RC0CH=CH(CH2)3CH=0, catalysed by the quinine-derived thiourea (288b) (<96% ee), followed by the tetramethyl guanidine (TMG)-catalysed retro-Henry-Henry reaction of the initially formed disubstituted cyclohexanols, led to a refinement of diastereoselectivity (to >99 1 dr) ... 

In 2011, Wang et al disclosed a highly enantioselective domino double Michael reaction of dienones with 3-nonsubstituted oxindoles to access chiral spirocyclic oxindoles in high yields of up to 98% and excellent dia-stereo- and enantioselectivities of up to >90% de and 98% ee, respectively. This novel reaction was performed in the presence of a cinchona-based... 

In 2012, a chiral cinchona alkaloid-derived primary amine was associated by Wang et al. to a (R)-BINOL-derived phosphoric acid to induce a three-component domino Knoevenagel-Michael reaction between isatins, malononitrile, and acetone, providing the corresponding domino products in generally excellent yields and enantioselectivities, as shown in Scheme 2.13. A hypothetic cooperative catalysis can be envisaged to explain these excellent results. 

In another context, Frechet et al. have described a polarity-directed three-component domino Henry-Michael reaction of two aliphatic aldehydes with different polarities and nitromethane catalysed by a combination of chiral diphenylprolinol trimethylsilyl ether and L-proline. In this original process. 

Scheme 7.48 Domino oxidation-Michael reaction catalysed by chiral amine catalysis and manganese catalysis.

Scheme 7.55 Three-component domino Henry-Michael reaction catalysed by microencapsulated amine catalysis and chiral nickel catatysis.

With regard to aldol chemistry, Mannich or domino-Mannich-Michael reactions can also be promoted by N-arylsulfonyl-substituted prolinamide catalysts such as 17 with high levels of enantioselectivity [82, 83). 

Anionic domino processes are the most often encountered domino reactions in the chemical literature. The well-known Robinson annulation, double Michael reaction, Pictet-Spengler cyclization, reductive amination, etc., all fall into this category. The primary step in this process is the attack of either an anion (e. g., a carban-ion, an enolate, or an alkoxide) or a pseudo anion as an uncharged nucleophile (e. g., an amine, or an alcohol) onto an electrophilic center. A bond formation takes place with the creation of a new real or pseudo-anionic functionality, which can undergo further transformations. The sequence can then be terminated either by the addition of a proton or by the elimination of an X group. 

Scheme 2.1. Twofold anionic domino reaction initiated by a Michael addition.

Scheme 2.7. Domino Mukaiyama/Michael/aldol reactions catalyzed by Sml2(THF)2.

Alkenones were used by Rao and coworkers [40] to prepare cyclohexane derivatives which, for example, can be transformed into substituted arenes in a single step. Another interesting intermolecular Michael/intramolecular aldol reaction sequence for the construction of the highly substituted 2-hydroxybicy-clo[3.2.1]octan-8-one framework has been described by Rodriguez group [41]. This process can be extended to a three- and even a fourfold domino reaction [41a, 42, 43],... 

A novel cyclopropanation method based on a domino l,4-addition/SN sequence has recently been described by Florio and coworkers [95]. A diastereoselective Michael reaction of lithiated aryloxiranes 2-174, obtained from 2-173, onto an a,(3-un-... 

It should be noted that several domino reactions exist where the Michael/SN-type... 

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... 

Yamamoto s group recently published a highly enantioselective chiral amine-catalyzed domino O-nitroso aldol/Michael reaction of 2-268 and 2-269 (Scheme 2.63) [141]. As products, the formal Diels-Alder adducts 2-271 were obtained with >98% 66, which is probably due to the selective attack of an enamine, temporarily formed from amine 2-270 and enone 2-268, onto the nitroso functionality. 

Scheme 2.63. Organocatalytic synthesis of 2-271 by a domino O-nitroso-aldol/Michael reaction.

Scheme 2.70. Asymetric domino Knoevenagel/Michael addition reaction.

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