Synthese makrocyclischer Ketone durch Ringerweiterung; ein neuer Weg zu(±)‐Muscon

Abstract

Synthesis of Macrocyclic Ketones by Ring-Enlargement Reactions; a New Path to (+)-MusconeA new synthetic route to macrocyclic ketones is described. Starting from 2-nitrocycloalkanones, the ring-enlarged compounds of the type 4 and 5 were prepared in three steps. Reduction of the NOz group with Bu,SnH and azobisisobutyronitrile led in moderate yields to simple 8-keto-esters which were quantitatively hydrolyzed and decarboxylated to the ketones of the type 8 and 9. The interesting fragrances Exdfone@ @a) and (+)-muscone (9a) were prepared in this way in overall yields of 22 and 18 %, respectively.In [ 11 haben wir die Synthese a$ -ungesattigter y -0xolactone ausgehend von 2-Nitrocycloalkanon-Derivaten beschrieben. Als Zwischenprodukte wurden dabei nach einer Ringerweiterung 5-Nitro-2-oxocycloalkancarbonsaure-ester

A one-pot sequence for the efficient synthesis of highly functionalized macrocarbocycles or bridged 2,8-dioxabicyclo[3.2.1]octanes from 1-nitrobicyclic compounds

“…At this stage, we reasoned that it should be possible to combine the ring-opening process with a Nef reaction, 7 potentially leading to a one-pot synthesis of diastereomerically pure macrocarbocycles with a high degree of substitution and functionalization. To this end, we chose the sodium borohydride conditions, which we expected to be more amenable to combination with acidic conditions in a one-pot procedure, for safety reasons.…”

A Novel NO2/OH Exchange in α‐Nitro Ketones: A mechanistic investigation

“…-The syntheses of the compounds of the type 7-10 used as the starting materials for our mechanistic investigations are straightforward [3] [7][10] [I91 [25]. Michael addition of the CH-acidic a-nitro ketones 25a-f [26] to acrylaldehyde provided the aldehydes 26a -f, which were cyclized by base-catalyzed intramolecular aldol reactions to the p-hydroxy ketones 9 and 27b-f (Scheme 8).…”

“…In particular, a-nitro cycloalkanones have been thoroughly studied as substrates for the preparation of ring-enlarged carbocycles, lactones, and lactams. They have been used for the synthesis of the ketone fragrances (+)-muscone and E.ualtone~"' [3] [4], the lactones phoracantholide I (racemic [5] and enantiomerically enriched [6]), ( f )-dihydrorecifeiolide and (*)-I 5-hexadecanolide [5], the lactone antibiotic A 26771 B [7], the macrocyclic spermidine alkaloids ( + )-inandenin-10-01, inandenin-10-one, and (f)-oncinotine [S], and analogs thereof [9], and for the preparation of other macrocyclic frameworks such as cyclophanes [lo-121 or benzolactones [13]. Two different ring-enlargement types have been applied in these investigations : the ZIP reaction that incorporates the side chains of a-substituted a-nitro ketones 1 into the ring (7j,pe A , Scheme I ) and the ring-enlargement reaction that cleaves the one-atom bridge of bicyclic a-nitro ketones 4 (Type B, Scheme I).…”

“…The results of a series of relevant experiments are summarized in Scheme 2 and Table 1. The experiments were performed under standardi7ed conditions using four types of compounds: with 7a, the enol form of an a-nitro 1 J-dione and some homologs (compounds 7b, c), some analogs (8a-c; a-nitro 1, 3 …”

α-Nitration of Ketones via Enol Silyl Ethers. Radical Cations as Reactive Intermediates in Thermal and Photochemical Processes

“…Various α-nitro ketones are widely utilized as synthetic intermediates − since they are excellent precursors for carbon to carbon bond-forming reactions owing to the powerful activation of the α-hydrogen atom by the combined effect of the nitro and carbonyl groups. , Furthermore, the facile cleavage of the C−C bond between the carbonyl and the nitro-substituted carbon atom in α-nitro ketones can be exploited in the synthesis of ring-enlarged cycloalkanones. , Although general methods for the efficient preparation of α-nitro ketones are desirable, the most direct route involving the electrophilic nitration of ketones (with nitric acid) suffers from a variety of oxidative byproducts enol acetates, and enol ethers, coupled with milder nitrating agents such as alkyl nitrates, nitryl chloride, and acyl nitrates, etc ., does facilitate the α-nitration of ketones, but their use has generally met with limited success …”