C−C versus C−O Anionic Domino Cycloalkylation of Stabilized Carbanions: Facile One-Pot Stereoselective Preparation of Functionalized Bridged Bicycloalkanones and Cyclic Enol Ethers

Abstract

alpha,alpha'-Diactivated cyclic- or acyclic ketones undergo a chemoselective base promoted (K2CO3, DBU) one-pot C-C cycloalkylation, with 1,3- and 1,4-dihalides having a cis-like fixed configuration. This reaction gives highly functionalized bicyclo[3.2.1]octan-9-one and bicyclo[4.2.1]nonan-9-one derivatives, which are easily transformed to seven- and eight-membered rings through a high yield retro-Dieckmann cleavage. Starting from trans-1,4-dibromo-2-butenes, the transformation is governed by stereoelectronic factors and leads, through a chemo- and stereoselective C-O cycloalkylation, to synthetically valuable monocyclic or fused polycyclic functionalized enol ethers of high synthetic value. Semiempirical calculations showed a small difference in energy and the late character of the transition states leading to cis and trans isomers of the corresponding fused polycyclic enol ethers. These results, although minimizing the influence of a destabilizing 1,3-interaction on the outcome of the reaction, are qualitatively in agreement with the experimental results.

Selective Construction of Carbocyclic Eight‐Membered Rings by Ring‐Closing Metathesis of Acyclic Precursors

“…Two indirect approaches were proposed as alternative routes for the synthesis of eight-membered rings through RCM. The concept is based on the formation of a temporary bridge [75][76][77] in correctly functionalized bridged bicyclic derivatives followed by selective strategic bond fragmentations of these strained intermediates. Mascareaeas and co-workers [78] introduced the selective formation/fragmentation of bicyclo-[3.3.1]nonanones with a hydroxy group at the bridgehead (Scheme 40).…”

Syntheses and Applications of Functionalized Bicyclo[3.2.1]octanes: Thirteen Years of Progress

“…55 For example, the cyclopentanone derivative 96 reacted with the 1,3-bishalides 97a−c to give the 3-alkyl-(or aryl)-idene bicyclo[3.2.1]octan-8-ones 98a,b in good yields (Scheme 35). The method has found more applications for the preparation of bicyclo[4.2.1]octan-9-one derivatives due to better availability of cis-1,4-dihalides.…”

“…Some of the recent examples include the fragmentation of substrates 85a−c with formic acid, 51b 98a,b 55 and 137a,b 73a with methanol, and a series of quinone−styrene [5 + 2]-cycloadducts with primary amines. 167 Coquerel, Rodriguez, and co-workers have developed a three-component approach to seven-membered rings from activated cyclopentanones, acrylic derivatives, and methanol, based on a domino Michael−aldolization−retroDieckmann (MARDi) cascade.…”

Consecutive reactions with sulfoximines: a direct access to 2-sulfonimidoylylidene tetrahydrofurans and 6-sulfonimidoylmethyl-3,4-dihydro-2H-pyrans

“…16 Several methods 17 have been developed for the construction of these useful building blocks 18 but there is still an interest in the development of an efficient, convenient and stereoselective approach. The regio-and diastereoselective synthesis of 2-ylidene tetrahydrofurans via anionic domino or consecutive reactions has been developed in the past few years independently in our group 8,19 and the groups of Zhao, 20 Hagiwara 21 and Langer. 17c In this context, chiral sulfoximines particularly turned our attention due to the presence of a modulable stereogenic sulfur atom and their use in asymmetric synthesis is well-established.…”