Acid-catalyzed [4+3] cycloaddition reaction of N-nosyl pyrroles

Direct Synthesis of Polycyclic Tropinones by a Condensation–[4+3]‐Cycloaddition Cascade Reaction

“…have just reported first intramolecular [4+3] cycloaddition reaction of pyrroles by using epoxy enolsilanes as a source of the oxyallyl cation . On the other hand, we have recently found that N ‐nosyl pyrrole is an efficient four‐carbon unit for [4+3] cycloaddition reaction, and the reaction with 2‐(silyloxy)‐acrolein 2 a as a three‐carbon unit is smoothly catalyzed by Cu(OTf) 2 or Sc(OTf) 3 . Therefore, we expected that an intramolecular [4+3] cycloaddition would be possible by the generation of an oxyallyl cation from some precursor possessing both N ‐nosyl pyrrole and 2‐(silyloxy)‐acrolein units as shown by A in Scheme .…”

“…We first attempted the reaction of N ‐nosyl‐2‐hydroxypropyl pyrrole 1 a to investigate whether the hydroxypropyl group could serve as the tether for the proposed cascade reaction (Table ). Thus, we initially applied the conditions of the intermolecular [4+3] cycloaddition reaction of N ‐nosyl pyrroles to 1 a , that is, 1 a was treated with 2 a in the presence of a catalytic amount of Cu(OTf) 2 in nitromethane at 0 °C . As we expected, the use of 20 mol % of Cu(OTf) 2 afforded the desired tricyclic tropinone 3 a in 58 % yield as a single diastereomer (entry 1).…”

“…[7] On the other hand, we have recently found that N-nosyl pyrrole is an efficient four-carbon unit for [4+ +3] cycloaddition reaction, [8] and the reactionw ith 2-(silyloxy)-acrolein 2a as a three-carbon unit is smoothly catalyzed by Cu(OTf) 2 or Sc(OTf) 3 . [9,10] Therefore, we expected that an intramolecular [4+ +3] cycloaddition would be possible by the generation of an oxyallyl cation from somep recursor possessing both N-nosyl pyrrole and 2-(silyloxy)-acrolein units as shown by A in Scheme1.Furthermore, since the preparation of such aprecursor might be troublesome due to the high reactivity of pyrroles, we planned to generate an oxyallylc ation in situ by the condensation of the aldehyde of 2-(silyloxy)-acrolein with nucleophiles such as hydroxyl, amino,a nd thiol groups that are tethered by the N-nosyl pyrrole. This method would provide easier access to ac ycloaddition precursor,w hich is expected to be amenable to aw ide range of substrates.…”

“…Thus, we initially applied the conditions of the intermolecular [4+ +3] cycloaddition reaction of N-nosyl pyrroles to 1a,t hat is, 1a was treated with 2a in the presence of ac atalytic amount of Cu(OTf) 2 in nitromethane at 0 8C. [9] As we ex-pected, the use of 20 mol %o fC u(OTf) 2 afforded the desired tricyclict ropinone 3a in 58 %y ield as as ingle diastereomer (entry 1). The structure of 3a was unambiguously confirmed by X-ray crystallographic analysis( see Supporting Information).…”

Pyrroles as Dienes in (4+3) Cycloadditions

“…Namba, Tanino and co-workers designed sulfur-and oxygen-substituted siloxyallylic alcohol derivatives 47a and 47b, respectively, to generate heteroatom-stabilized siloxyallylic cations upon acid-induced dehydration (Scheme 11). 51,52 N-Acetyl-, N-benzyl-, and N-Cbz-protected, and unprotected pyrroles all failed to undergo cycloaddition; only N-sulfonylated pyrroles reacted, of which the most electron-deficient nosyl-protected 1f reacted with the highest cycloaddition yields. These results suggested that electronwithdrawing effect of the pyrrole protecting group, rather than its steric bulkiness, exerted a greater impact to facilitate the (4+3) cycloaddition.…”