Construction of 8-Azabicyclo[3.2.1]octanes via Sequential DDQ-Mediated Oxidative Mannich Reactions of N-Aryl Pyrrolidines

Abstract

A concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative Mannich reactions is described. This approach involves an intermolecular oxidative Mannich coupling reaction between N-aryl pyrrolidines with TMS enol ether and a subsequent intramolecular oxidative Mannich cyclization of the corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.

Green and Efficient Esterification Method Using Dried Dowex H+/NaI Approach

“…Only three examples to prepare acetylated tropic acid ( 41 ) from tropic acid ( 1 ) were found in the literature, according to SciFinder search, all utilizing acetyl chloride. 26 The isobutyl derivative ( 42 ) was totally unknown. By adopting the Dowex H + /NaI approach with tropic acid ( 1 ) and acetic or isobutyric acid, 99 and 44% isolated yields (99 and 88% conversions; see Table 2) were achieved for compounds 41 and 42 , respectively.…”

DDQ as a versatile and easily recyclable oxidant: a systematic review

“…The key oxidant utilized for these reactions was DDQ. 39 The ether moiety is well known of its inertness, justifying the use of tetrahydrofuran and diethyl ether, among others, as solvents in organic synthesis. Thus, the selective oxidation of ethers is challenging in synthetic chemistry, oen resulting in low yield and selectivity.…”

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…The synthesis of 1-(pyrrolidin-2-yl)propan-2-one derivatives described in this section is based mainly on different variants of the Michael reaction. Thus, the Mannich oxidative reaction between N-arylpyrrolidines 21 and trimethyl(prop-1-en-2-yloxy)silane, leading to norhygrine derivatives 22, is described in the works of Cho and Min and of Klussmann (Scheme 6,a), [36,37] the oxidizing agent in this reaction is 2,3-dichloro-5,6dicyanoquinone (DDQ). The authors note that the low reaction temperature is of great importance for the formation of the target product in high yield.…”