1,4-Dioxamacrolides: Preparation and Sensory Properties

Abstract

The synthesis of 3-methyl-1,4-dioxacylopentadecan-2one (12c) and 3-methyl-1,4-dioxacylohexadecan-2-one (12d), two new musk odorants, is described starting from methyl 2-bromopropionic acid (6b) and allylic alcohol, respectively. The key step of the synthesis is the ring-closing olefin metathesis (RCM) to the unsaturated 1,4-dioxamacrolides. Insight into the structure-odor relationship (SOR) is provided by the synthesis of ten related unsubstituted or methyl substituted oxamacrolides. Finally, a four step enantioselective synthesis of both (3R)-(+)-and (3S)-(-)-3-methyl-1,4-dioxacyclopentadecan-2-one as well as (3R)-(+)-and (3S)-(-)-3-methyl-1,4-dioxacyclohexadecan-2-one reveals that mainly the (3R)-(+) enantiomers are responsible for the powerful musky odor characteristic. Their synthesis starts from ethyl (2S)-2hydroxypropanoate (14) or isobutyl (2R)-2-hydroxypropanoate (15) which were treated under acidic conditions with allyl trichloroacetimidate (16), followed by titanate mediated transesterification, ring-closing olefin metathesis and hydrogenation.

Direct Decarboxylative Allylation and Arylation of Aliphatic Carboxylic Acids Using Flavin‐Mediated Photoredox Catalysis

“…General Procedure for the Synthesis of 3qa and 7: 2-(but-3-en-1-yloxy)propanoic acid [40] (1q) (28.8 mg, 0.2 mmol, 1 equiv.) was added to a 2 dram vial equipped with a stirring magnetic bar, followed by RFTA (5.44 mg, 0.01 mmol, 5 mol-%), and a solution of 2a (0.22 mmol, 56.4 mg, 1.1 equiv.)…”

Metátese de olefinas aplicada ao fechamento de anéis: uma ferramenta poderosa para a síntese de macrociclos naturais

“…Nestas condições, o ácido de Lewis entra em competição com as espécies rutênio-carbenos pela coordenação com os sítios básicos do substrato, permitindo a formação dos produtos ciclizados. Como exemplos de uso de Ti(Oi-Pr) 4 , pode ser citada a síntese das molécu-las odorantes de estrutura dioxa-macrocíclica 20 realizada por Eh, onde foi observada a influência negativa da função éter na conversão da reação de RCM (Esquema 6) 40 . Os produtos cíclicos 19 só foram obtidos, em excelentes rendimentos, utilizando o catalisador de rutênio 3 em presença de quantidade catalítica de Ti(Oi-Pr) 4 .…”