Domino reactions allylic substitution

Tu, Li, and coworkers also developed a new allylic functionalization without the use of metal catalysts [59-61]. Efficient annulation of enaminones 57 with arylglyoxal monohydrates 58 and the subsequent allylic functionalization with aliphatic carboxylic acids 38 as nucleophile reagents provided multifunctionalized indoles 98 with 75-89% yields (Scheme 12.38) [59]. To further explore the scope of this domino reaction, N-substituted 3-aminocyclohex-2-enones were employed. Interestingly, two molecules of arylglyoxal mono hydrate and N-substituted... 

Most studies on nickel-catalyzed domino reactions have been performed by Ikeda and colleagues [287], who observed that alkenyl nickel species, obtained from alkynes 6/4-41 and a (jr-allyl) nickel complex, can react with organometallics as 6/4-42. If this reaction is carried out in the presence of enones 6/4-43 and TM SCI, then coupling products such as 6/4-44 are obtained. After hydrolysis, substituted ketones 6/4-45 are obtained (Scheme 6/4.12). With cyclic and (5-substituted enones the use of pyridine is essential. Usually, the regioselectivity and stereoselectivity of the reactions is very high. On occasion, alkenes can be used instead of alkynes, though this is rather restricted as only norbornene gave reasonable results [288]. 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

Keywords Allylic substitution CH activation Cross-coupling Cycloisomerization Domino reactions Metallation Multicomponent reactions Palladium catalysis... 

An intriguing showcase for polycyclizations based upon hetero-domino reactions is outlined in Scheme 30, where the catalyst 89 gives rise to the formation of a mixture of indolone skeletons 92-94 with a preference for the generation of tetracycle 94 as a result of an intramolecular allylic substitution-Heck sequence. 

Domino reactions have attracted significant attention given that this methodology enables multistep synthesis to be completed in one pot. The early work done by Jeong et al. used a dual-catalyst system for the preparation of bicyclopentenone 339. A palladium complex was used to catalyze the allylic substitution of 556 to form the enyne intermediate 338. Subsequent Rh-catalyzed Pauson-Khand reaction furnished the desired product 339 in high yield (Scheme 2-91). ... 

Scheme 2-91. Reductive domino allylic substitution and Pauson-Khand reaction.

The bicyclization commences with the hydroformylation of an appropriate N-substituted allyl amide, producing the linear aldehyde as the main product. The compound undergoes spontaneous intramolecular cyclization. The final product of this domino reaction is formed by the reaction with the solvent (AcOH). Subsequent oxidation of the acylic keto group to the corresponding ester and reduction with LiAlH produced the targeted racemic natural compound with 33% overall yield over four steps. 

In an effort to further evaluate the generality of this concept, we were particularly attracted to evaluate novel methods for the synthesis of chiral 1,3-diamine motifs and of 1,3-aminoalcohol functionahties, both of which constitute particularly important structural elements in various bioactive natural products and medicinal compounds. Because of their prevalence, a number of strategies for the construction of such systems have been reported. Inspired by our domino concept in combination with certain hmitations of existing methods, in particular, with respect to modularity and convergence, a more direct and flexible procedure for 1,3-diamine and 1,3-amino alcohol synthesis based on stereoselective intramolecular allylic substitution reaction seemed desirable. 

The most important ruthenium-catalyzed domino process is based on a metathesis reaction. Nonetheless, a few other ruthenium-catalyzed processes have been employed for the synthesis of substituted 3,y-unsaturated ketones, as well as unsaturated y-lactams and allylic amines. 

Plumet et al. described domino metathesis of propargyl (2-endo-7-oxanorborn-5-enyl) ethers 62a-62c with allyl acetate in the presence of Grubbs ruthenium catalyst Ic (Scheme 22). The reaction proceeds stereoselectively to produce substituted m-fused bicyclic ethers 63a-63c. In a similar manner, indolizidinone derivative 64 is obtained from compound 62d instead of pyrrolizidine derivative 63d. ... 

Chen and coworkers published a formal [3 + 3]-type reaction to give highly substituted cyclohexenes 8. This domino process consists of an allylic-allylic alkylation of an a,a-dicyanoalkene derived from 1-indanone and Morita-Baylis-Hillman carbonates, following an intramolecular Michael addition, by employing dual orga-nocatalysis of commercially available modified cinchona alkaloid (DHQD)2AQN If (hydroquinidine (anthraquinone-l,4-diyl) diether) and (S)-BINOL. The cyclic adducts... 

Coupling of CM and intramolecular substitution to domino processes leading to tetrahydrofurans is feasible as well [38]. However, a corresponding combination to give tetrahydropyrans is better carried out as a sequential process [38d]. Reaction of the terminal olefin 184 with allyl chloride catalyzed by ruthenium complex 2 led to tetrahydrofuran 185 by a completely diastereoseleclive cyclization of the intermediate CM product (Scieme 2.65) [38a,b]. Compound 185 was then successfully advanced to the immunosuppressive diterpenoid pyrone subglutinol B. 

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