Toward a Symphony of Reactivity: Cascades Involving Catalysis and Sigmatropic Rearrangements

Abstract

Catalysis and synthesis are intimately linked in modern organic chemistry. The synthesis of complex molecules is an ever evolving area of science. In many regards, the inherent beauty associated with a synthetic sequence can be linked to a certain combination of the creativity with which a sequence is designed and the overall efficiency with which the ultimate process is performed. In synthesis, as in other endeavors, beauty is very much in the eyes of the beholder.[**] It is with this in mind that we will attempt to review an area of synthesis that has fascinated us and that we find extraordinarily beautiful, namely the combination of catalysis and sigmatropic rearrangements in consecutive and cascade sequences.

Development of a Phase-Transfer-Catalyzed, [2,3]-Wittig Rearrangement

“…The crystals were ground using a glass stir rod then dried in a drying pistol (over P 2 O 5 /refluxing dichloromethane) under vacuum (0.1 mmHg) for 18 h, then at rt for 24 h. Data for 1-isopropylisatin: mp 57−58°C; 1 H NMR (500 MHz, CDCl 3 ) 7.61 (dd, J = 7.4, 0.7 Hz, 1 H, HC (5)), 7.56 (td, J = 7.9, 1.4 Hz, 1 H, HC(7)), 7.09 (t, J = 7. 5 Hz, 1 H, HC (6)), 7.03 (dd, J = 8.1, 0.9 Hz, 1 H, HC (8) (2)), 150.6 (C(4)), 138.2 (HC (7)), 125.7 (HC (6)), 123.4 (HC (5)), 118.0 (C(9)), 111.4 (HC (8)), 44.9 ((H 3 C) 2 HC (1) Preparation of 3-Diazo-1-isopropylindolin-2-one. To a 250-mL, single-neck, round-bottomed flask with Ar inlet and stir bar was added 1-isopropylindoline-2,3-dione (7.18 g, 37.21 mmol, 1.0 equiv).…”

“…Two additional substrates were prepared that contained additional substituents on the alkene (12b) or a different N-protecting group (12c). These substrates were also tested under the standard reaction conditions (5 M aq KOH/toluene,(3)(4)(5). Dimethyl substitution at the terminus of the alkene was well tolerated and this substrate showed similar reactivity to the parent substrate 12a (entries [13][14][15].…”

“…H), 8.33 (d, J = 8.5 Hz, 1 H), 8.17 (dd, J = 6.6, 2.3 Hz, 1 H), 8.14− 8.10 (m, 2 H), 7.96 (dd, J = 4.6, 0.9 Hz, 1 H), 7.85 (ddd, J = 8.4, 6.9, 1.5 Hz), 7.81 (ddd, J = 8.3, 6.9, 1.5 Hz, 1 H), 7.57 (dd, J = 10.3, 8.5 Hz, 1 H), 6.64 (br s, 1 H), 5.68 (ddd, J = 17.2, 10.5, 6.7 Hz, 1 H), 5.29 (d, J = 12.6 Hz, 1 H), 5.18 (d, J = 12.6 Hz, 1 H), 5.17 (d, J = 17.2 Hz, 1 H), 5.00 (dt, J= 10.5, 1.2 Hz, 1 H), 4.50 (ddp, J = 10.8, 8.4, 2.9 Hz, 1 H), 4.03 (ddt, J = 10.5, 8.4, 2.1 Hz, 1 H), 3.73 (ddd, J = 12.6, 4.9, 3.1 Hz, 1 H), 3.47 (dd, J = 12.6, 10.6 Hz, 1 H), 3.38 (tdd, J = 11.4,5.0, 1.8 Hz, 1 H), 2.77−2.69 (m, 1 H), 2.33−2.19 (m, 2 H), 2.08 (q, J = 3.1…”

Tandem Claisen Rearrangement/6‐endo Cyclization Approach to Allylated and Pren­ylated Chromones

“…[26] Recently, approaches to Cprenylated or -allylated flavonoids and isoflavonoids have emerged that rely on a tandem (or domino) prenylation (or allylation) and cyclization sequence. [27][28][29] Examples are the syntheses of 3-allyl-substituted chromones [30,31] and isochromones [32] in which a metal-catalysed or electrophilic alkynone cyclization and a concomitant allyl migration are combined. Motivated by the discovery of two new 8-substituted chroman-4-ones, tabchromones A and B, from the tobacco plant nicotiana tabacum, [33] we have very recently developed a synthesis [34] based on a microwave-promoted allyl aryl ether Claisen rearrangement and subsequent 6-endotrig cyclization.…”

Enantioselective synthesis of decalin structures with all-carbon quaternary centers via one-pot sequential Cope/Rauhut–Currier reaction

“…Tandem or sequential reactions have been an important tool in this regard 1–12 . Herein we report a one-pot intramolecular Cope/Rauhut-Currier sequence which illustrates the potential for the efficient enantioselective construction of functionalized decalin structures ( 3 , Scheme 1).…”