Domino Michael/intramolecular

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

Application of this work to a domino process using 51 involves Michael addition of P-ketoesters [91], p-diketones or P-ketosulfones [92] to a,P-unsaturated ketones followed by an intramolecular aldol reaction provides highly functionalised cyclohexanone building blocks with up to four contiguous chiral centres. Gryko has also reported examples of this domino Michael/intramolecular aldol reaction in the coupling of 1,3-diketones and methyl vinyl ketone using L-proUne as catalyst [93],... 

Fig. 10 Catalytic cycle for the organocatalytic domino Michael/intramolecular aldol condensation...

A large number of enantioselective domino Michael/intramolecular heterocyclization reactions have been successfully developed in the last years, using three... 

SCHEME 16.19. Enantioselective domino Michael/intramolecular cylization reaction. 

Scheme 2.17. Intramolecular domino Michael/aldol process initiated by the addition of halide to an enone.

Besides this unique above-described process, there a numerous examples of inter- and intramolecular domino Michael/aldol processes in which the sequence is initiated by the addition of a metalorganic compound to an enone moiety. The Kamimura group [30] synthesized several five- to seven-membered thio- and hy-... 

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],... 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

Using diarylprolinol ether 55 in conjunction with an additional base, a domino Michael/aldol/intramolecular Sj 2 process has been developed that led to highly functionalised epoxy cyclohexanones 110, with excellent control of three of the chiral centres generated (Scheme 42) [169]. Despite the apparent complexity, these reactions proceed at room temperature in less than 24 h and the products contain significant potential for a host of further transformations. 

Scheme 42 Organocatalytic domino Michael/aldol/intramolecular S 2 reactions...

A stereoselective synthesis of substituted pyrrolidines has been achieved by a sequential domino Michael addition and intramolecular carbozincation. The intermediate zinc-copper reagent obtained after cyclization can be trapped with an electrophile such as allyl bromide (Scheme 18).180 Addition of zincated hydrazones 52 on alkenyl boronates, followed by a trapping with an electrophile, provides adduct of type 53 with good yield and high diastereoselectivity (Scheme 19).181 By this addition/trapping sequence, several contiguous stereogenic centers are created in one step. 

A variety of a,a-dicyanoalkenes derived from aryl ketones have also been extensively explored under the same catalytic conditions, and in general the vinylogous Michael adducts were obtained due to the steric hindrance in the following enamine catalysis by primary amine lo [28]. Nevertheless, an interesting domino Michael-Michael-retro-Michael reaction was observed for a,a-dicyanoalkenes derived from acetophenone and propiophenone, giving a facile process to chiral 2-cyclohexen-l-one derivatives. It was noteworthy that a kinetic resolution was observed in the intramolecular Michael addition step (Scheme 10.22). 

The Baylis-Hillman reaction of pyran-4-ones and chromones with aldehydes is efficiently catalysed by NaOMe or DBU <04JOC8413> and when applied to salicylaldehyde and cyclohexenone a tetrahydroxanthen-l-one results possibly via a domino Michael addition and intramolecular aldol condensation <04AG(E)115>. 

Scheme 3.85 Organocatalytic one-pot asymmetric synthesis of bicyclic isoxazolidines by domino Michael addition/in situ condensation/intramolecular nitrone [3-1-2] cycloaddition sequence...

An intramolecular domino Michael/aldol reaction starting from the chiral Cope products 58 was developed by the group of Schneider [27], After 1,4-addition of... 

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