Cyclododecanone, ring expansion

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

This hypoiodite reaction can also be used for ring expansion of cyclic ketones.2 Thus Barbier cyclization of a-(w-iodopropyl)cyclododecanone (3) furnishes the bicyclic alcohol 4, which undergoes regioselective cleavage to a 15-membered iodo... 

Production. The main industrial syntheses start from compounds produced from cyclododecatriene either by ring expansion of cyclododecanone or by depolymerization of polyesters of 15-hydroxypentadecanoic acid (from 1,12-dodecanediol). 

Preparation by Ring Expansion of Cyclododecanone. Radical addition of allyl alcohol to cyclododecanone, for example, with di-/cr/-butyl peroxide as a radical initiator, yields 2-(7-hydroxypropyl)cyclododecanone. This is converted into 13-oxabicyclo[10.4.0]hexadec-l(12)-ene by acid-catalyzed dehydration [202], Addition of hydrogen peroxide, in the presence of sulfuric acid, gives 12-hydroperoxy-13-oxabicyclo[10.4.0]hexadecane. Cleavage of the peroxide by heating in xylene gives 15-pentadecanolide as well as a small amount of 15-pentadec-l l(and 12)-enolide and 12-hydroxy-15-penta-decanolide [203]. 

A method of repetitive ring expansion of cyclic ketones was published based on the use of (phenylseleno)acetaldehyde on the siloxy-Cope rearrangement [29a], The authors were able to transform cyclododecanone into cycloeicosadec-5-en-l-one in 23 % yield. 

This ring expansion has been applied to the synthesis of the 15-membered ( )-muscone [37], First cyclododecanone was tranformed to cyclotridec-3-enone (V/67) in a five step synthesis [38]. The latter, treated with the Grignard reagent formed from prop-l-enyl bromide, generated a mixture of the isomeric compounds, V/68, in nearly 50 % yield. Obviously the methyl group sterically... 

Bicyclo[10.3.0]-A -pentadecen-14-one (25) was prepared from cyclododecanone. Allylation of the 3-keto ester (23) and the oxidation of the terminal alkenic bond afforded the 1,4-diketone (24) in 72% yield from the 3-keto ester. Base-catalyzed cyclization and deethoxycarbonylation gave die bicycloketone (25), which was converted to muscone (26 Scheme 7). Thus, this is a method for three-carbon ring expansion. 

One of the best examples for three-carbon ring expansion is the total synthesis of DL- and (/ )-muscone starting from a cyclododecanone derivative [5, 13], A good yield of ring expansion product is obtained by the use of selenide as the radical precursor (Scheme 8). 

A useful one-carbon ring-expansion reaction which has been developed involves treatment of l-(dibromomethyl)-cycloalkan-l-ols with n-butyl-lithium in hexane to give the ring-expanded ketones, usually in excellent yield e.g. l-(dibromomethyl)-cyclododecan-l-ol, which was obtained by treating cyclododecanone with dibromo-methyl-lithium, gave cyclotridecanone in 89% isolated yield. ... 

Photolysis of 2-(2 -cyclopropylcyclopropyl)cycloalkanones (108 n = 1, 2) gave ring-expanded products e.g. (108 n = 1) gave a mixture of cyclododecanone (61 %) and 2-cyclopropylcyclononanone (20%). Ring expansion of cyclic mono- and diacetylenes by 4, 8 or 12 carbon atoms can be achieved by nickel-catalysed cyclooligomerization with buta-1,3-diene, followed by oxidative cleavage thus cyclo-tetradec-l,8-diyne was converted into cyclotriacontane. ... 

Cyclododecanone, which became the most accessible of medium-ring ketones following Wilke s discovery of the butadiene-cyclotrimerization process, is an important starting point for manufacture of the valuable musk ketones. Two syntheses of muscone, commencing from cyclododecanone are outlined below. The first synthesis, which emanated jointly from Eshenmoser s group in Zurich and laboratories of the Swiss perfume firm, Firmenich Cie., illustrates a three-carbon ring expansion reaction based on the widely applicable tosylhydrazone version of the oxidoketone— alkynone fragmentation. ... 

---