Muscone synthesis

Interesting results have been obtained in intramolecular acylation reactions involving pyrrole and thiophene derivatives. A muscone synthesis involves selective intramolecular acylation at a vacant a-position (Scheme 18) (80JOC1906). In attempts to prepare 5,5-fused systems via intramolecular acylation reactions on to a jS-position of a thiophene or a pyrrole, in some cases ipso substitution occurs with the result that rearranged products are formed (Scheme 19) (82TH30200). 

With unsymmetrical cyclic ketones, however, mixtures due to similar migratory aptitudes of the different groups are obtained (Table 13, Nos. 2, 3). The rearrangement has also been used as key step in a d,/-muscone synthesis (Table 13, No. 4). 

Scheme 34 1,2-Rearrangement induced by the Non-Kolbe reaction as key step for a muscone synthesis.

Takahashi, T. Ebata, S. Doi,T. Solid Phase Approach to Muscone Synthesis Rh(I)-Catalysed Hydroformylation of a 1,1-Disubstituted Alkene on the Multipin1 System, Tetrahedron Lett. 1998, 39, 1369. 

Scheme IX/11. Part of a muscone synthesis in which the alcoholate acts as an internal leaving group [31].

Wolfgang Oppolzer s muscone synthesis is the first enantioselective macrocycli-sation. [195] It starts with pentadec-14-ynal, which is converted by hydro-boration and transmetaUation into the corresponding organozinc compound. The ring closure takes place in the presence of catalytic amounts of a diethylzinc/ (-)ejco-3-(diethylamino)bomeol adduct. After work-up, the cyclic allyl alcohol is obtained in 75 % yield and with an ee of 92 %. The hydroxy-group directs the diastereoselective cyclopropanation (Simmons-Smith reaction). The final steps are a Swern oxidation and selective ring-opening of the cyclopropane under Birch conditions. 

The high-dilution Dieckmann condensation of m-benzenedialkanoic esters (89 n = 2, 3,4) was found to give dimeric diketones for (89 n = 4) a minor monomeric product was obtained as well, but was not rigorously characterized. The ringforming step in a (+)-muscone synthesis is an acyloin condensation. ... 

Fig. 20 Asymmetric isomerization of allylic alcohol and its application to muscone synthesis...

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