Organocatalysts and sequential asymmetric cascade reactions in the synthesis of functionalized isoindolinones and benzoindolizidinones

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…[168] Massa andc o-workers devisedadomino strategyt o synthesize isoindolinones 436 from the reactiono f 402 and 379 using the quinine-derivedt hiourea 438 and urea 439 as the chiral catalysts ando btained benzoindolizidinones 437 from 436 via as equential Michael reaction( Scheme 112). [169] They also demonstrated that this strategy may be further extended to produce ent-436 and ent-437 by using 440 (Scheme 112) as ac hiral phase-transfer catalyst. [170] Enders and co-workers reported as tereoselective synthesiso fe nantioenriched tetrahydropyridines 442 with high yields and excellent stereoselectivities from the intermediates 441,which were formed via Michael addition reactions between nitroalkenes 76 and1 ,3-diketones 379,c atalyzed by aq uinine-derived squaramide 443 (Scheme 113).…”

3-Carboxylate-Substituted Isoindolinones in K2CO3-Catalyzed Michael Reactions

“…It is worthy to note that the developed new method, in comparison to others multi-steps reported in literature for the construction of related aza-tricyclic derivatives, [18] is particularly convenient in terms of efficiency and step-economy. Moreover, the concomitant formation of the hemi-aminal functionality, which could be subjected to other transformations as reported for the analogues benzolizidines, [13][14][15] is useful for further elaboration of the tricyclic scaffold. Depending on the tested unsaturated aldehydes, the methodology allows the obtaining derivatives with two or more stereocenters diastereoselectively.…”

“…To that purpose we exploit previous findings on the oxidation of hemi-aminal group of benzoindolizidines. [13][14][15] The removing of the stereocenter at the hemi-aminal functionality by PCC oxidation, led to the interesting imide derivative 5 with an unchanged dr with respect to 3b (Scheme 2).…”

“…[6][7][8][9][10][11][12] Surprisingly, at the best of our knowledge, isoindolinones, substituted in 3-position with an electron withdrawing group, have not been attractive as nucleophiles in this fundamental reaction. As part of our ongoing studies on the synthesis of biologically relevant heterocycles, [13][14][15] we describe herein an unprecedented Michael reaction of activated isoindolinones for the construction of 3,3-disubstituted derivatives. Furthermore, among the efforts in this area [16] and in connection with our findings in the preparation of tricyclic benzoindolizidines via K 2 CO 3 -catalyzed cascade Michael/cyclization reactions, [14,15] we report a very convenient approach for the synthesis of structurally related pyrrolizidines.…”

Palladium‐Catalyzed Carbonylation of 2‐Bromoanilines with 2‐Formylbenzoic Acid and 2‐Halobenzaldehydes: Efficient Synthesis of Functionalized Isoindolinones

“…[16] Massa and co-workers reported the first organocatalytic asymmetric synthesis of 3-substituted isoindolinones. [17] Recently, Lin and co-workers reported an efficient three-component reaction of 2-formylbenzoic acid, ammonia, and 4-hydroxycoumarin or indole in water, which leads to the formation of 3-heterocyclic-substituted isoindolinones in good yields. [18] [a] Dr. K. Natte, J.…”