Exaltone synthesis

The use of macrocyclic compounds of the thiophene series for the preparation of macrocyclic alicyclie ketones has been mentioned earlier. " A new synthesis of exaltone has been carried out using (136) as the starting material. ... 

Macrocyclic ketones. This reagent has been used for cycloolefination of acetylenic dialdehydes (Wittig-Horner reaction) as a route to muscone, exaltone, and civetone. A synthesis of the last ketone (3) is formulated (equation 1). 

In the synthesis of the following lactones, the oxygen atom has been introduced by Baeyer-Villiger rearrangement, e.g. ( )-phoracantholide I [137], ( )-lactone antibiotic A26771B [138], exaltone [139]. 

One step in a synthesis of d/-muscone (4) from exaltone (1) involved dehydiobromina-tion of (2). This was effected with l,5-diazabicyclo[4.3.0]noncne-5 in 70% yield. Treatment with pota.s.sium /-butoxide in t-butanol or DMSO afforded only the dioxine (5). ... 

Eschenmoser, A., Eelix, D., Ohioff, G. New fragmentation reaction of a,P-unsaturated carbonyls. Synthesis of exaltone and rac-muscone from cyclododecanone. Helv. Chim. Acta 1967, 50, 708-713. 

Eehr, C., Ohioff, G., Buchi, G. A new a,P-enone -> alkynone fragmentation. Synthesis of Exaltone and ( )-muscone. Helv. Chim. Acta 1979, 62, 2655-2660. 

The technical breakthrough was however only attained with the StoU-Hansley-Prelog procedure for the synthesis of exaltone. By reaction with sodium, dimethyl hexadecanedioate was converted into the acyloin, [174] the reduction of which with zinc and hydrochloric acid (Qemmensen reduction) gave exaltone. On the other hand, dehydration of the acyloin over hot aluminium oxide gave exaltenone, which could be converted by a copper(I)-catalysed reaction with methylmagnesium bromide into (+/-)-muscone. 

One of the first industrial muscone syntheses stems from work at BASF. [182] Analogous to the synthesis of exaltone, cyclododecanone is converted, by reaction with but-3-yn-2-ol, into a diol, which is further transformed by a Meyer-Schuster rearrangement and Nazarov cyclisation into a methyl-substituted bicycle. A very short route to the same product was described by Mitsui Petrochemical Industries a few years later this involved the direct conversion of cy-clododecene with crotonic acid in the presence of polyphosphoric acid, and resulted in a remarkable yield of 54 %. [183]... 

The formation of epoxy ketones from sterically crowded enones is often difficult. Avoiding the epoxi-dation step, fragmentation to give the alkynone (137 Scheme 47) occurs on treatment of the unsaturated hydrazones (145) (fiom 135) with an excess of I S in methanol. Ohloff and Bach used this sequence for a further synthesis of exaltone (118) and muscone (119). 

Similarly, in the synthesis of exaltone reported by Buchi and Wuest, " the yields in the key conversion of (226) into (227) are considerably enhanced by the presence of the internal double bonds. 

Scheme 32 Cycloalumination of cyclododecyne in the synthesis of Muscone and Exaltone...

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