Enantioselective Synthesis and X‐ray Structure of (+)((4aS,5S,8aS)‐5,8a‐Dimethyl‐7‐methyleneoctahydro‐2H‐spiro[naphthalene‐1,2′‐[1,3]dioxolan]‐5‐yl)methyl‐4‐iodobenzoate

Abstract

The d and l amino acid mediated enantioselective intramolecular aldol reaction of 4‐((1‐methyl‐2,6‐dioxo‐cyclohexyl)methyl)‐pent‐4‐enal 1 leading, after dehydration, to (‐)‐(R) and (+)‐(S) 4a‐methyl‐3‐methylene‐5‐oxo‐2,3,4,4a,5,6,7,8‐octahydro‐naphthalene‐1‐carbaldehyde 2 was explored. It was found that (‐)‐(R) carbaldehyde 2 is enantioselectively formed in the presence of l‐amino acids while (+)‐(S) carbaldehyde 2 is enantioselectively formed in the presence of d‐amino acids. (‐)‐(R) Carbaldehyde 2 was then transformed into (+)‐22. The absolute configuration and relative stereochemistry of the latter was established by single‐crystal X‐ray diffraction analysis of p‐iodobenzoate (+)‐23.

Organocatalyst Design for the Stereoselective Annulation towards Bicyclic Diketones and Analogues

“…In the proposed mechanism, the organocatalyst reacts with the aldehyde moiety of 99a to generate the enamine 101, which then reacts with one of the carbonyl groups via the transition state 102 to give iminium 103; the hydrolysis of the iminium ion generates the aldol product 104 with regeneration of the organocatalyst (Scheme 8). Subsequently, in 2019 Leonelli and co-workers reported the asymmetrical synthesis of 106, proposing it as useful starting material for the preparation of different diterpenes (Scheme 9) [100]. For this purpose, they tested different amino acids as organocatalysts of the intramolecular aldol reaction of the diketoaldehyde 105, and the best results were obtained with L-tyrosine C-3 or its enantiomer (1.1 eq), in DMSO, 1M HClO 4 , at 10 • C for 20 h, giving (R)-106 or (S)-106, respectively (80% yield, 86% ee).…”

Stemarane Diterpenes and Diterpenoids

“…Recently, the synthesis of the bicyclic intermediate 94 , necessary for the enantioselective obtaining of (+)-oryzalexin S 11 was described by our group (Scheme 15) [96].…”

Phosphonium Ion-Tethered Secondary Amines for Chemospecific 5-Enolexo Aldol Condensations of 6-Ketoaldehydes

“…The addition of either an acid or a base to the reaction is imperative to facilitate the removal of water to produce a C-C double bond. , Our study introduces the synthesis of a novel class of proline-derived alkylphosphonium salt (catalyst 1 ) as a catalyst, which serves as a powerful tool for enabling the direct, additive-free, and highly selective 5- enolexo aldol condensation of 6-ketoaldehydes. In this particular context, both carbonyl groups exhibit enolizability, devoid of any geometric constraints, and are capable of accessing distinct reaction pathways that include an intermolecular aldol reaction (Scheme ). Nonetheless, employing 1 predominantly leads to the kinetically favored aldol condensation product a .…”