P r e p a r a t i o n o f 1 , 2 -D i k e t o n e s a n d t h e i r M o n o x i m e A n a l o g s Abstract: Treatment of a-methylene ketones with excess sodium nitrite and aqueous HCl in THF at reduced temperatures provides an effective tool for the preparation of a variety of 1,2-diketones. The diastereoselective synthesis of the corresponding (Z)-1,2-dione monoximes could be accomplished under similar conditions, but by using only one equivalent of nitrosating reagent.

A thermal three-carbon ring expansion based on side chain ring insertion of a cyclopropane moiety is described. Flash vacuum pyrolysis (FVP) of 1-cyclopropyl-cycloalk-3-enol derivatives leads to the three-carbon ring expanded enones with clean retention of double bond geometry. Substrates bearing methyl groups on the cyclopropane ring undergo regioselective bond cleavage, allowing for the systematic preparation of selectively substituted macrocyclic musks from low-priced C-12 starting compounds.

The substituted isoborneols 1a ± 1g and 5,6-dehydroisoborneols 6a ± 6c, readily prepared in excellent yields from ()-camphor and ()-5,6-dehydrocamphor (2) by aryl, vinyl, or alkyl Grignard addition in the presence of stoichiometric amounts of CeCl 3 , were thermally isomerized in a flow reactor system under DGPTI (dynamic gas-phase thermo-isomerization) conditions at temperatures between 480 and 6308 to give the enantiomerically pure monocyclic carbonyl compounds 7a ± 7d, 19a, b, 23, and 24. In all cases, product formation proceeded highly regio-as well as stereoselectively. The absolute configurations of the new stereogenic centers were determined by 1 H-NOE measurements. DGPTI of the aryl substrates 1a ± 1d is proposed to effect initial cleavage of the weakest single bond in the molecule under formation of a diradical intermediate state followed by intramolecular H-abstraction to afford the acetophenone derivatives 7a ± 7d. This reaction path was further supported by a 2 H-labeling study showing the OH group to be the exclusive H-source. In contrast, DGPTI of the vinyl substrates 1e and 6b allowed concerted retro-ene and oxy-Cope rearrangements. In the case of 5,6-dehydro-2-phenylisoborneol (6a), concomitant diradical and retro-DielsÀAlder reaction pathways could be observed. In addition, a new route to ()-trans-a-campholanic acid (9) and ()-trans-a-dihydrocampholytic acid (14) is presented by regioselective BaeyerÀVilliger oxidation and subsequent hydrolysis of 7c and 7d, respectively.

A new method for the smooth and highly efficient preparation of functionalized macrocyclic ketones has been developed. Pyrolysis of medium‐ and large‐ring 3‐vinylcycloalkanones by dynamic gas‐phase thermo‐isomerization (DGPTI) at 600–630° yielded, under insertion of a previously attached vinyl side chain by means of a 1,3‐C shift, the corresponding γ,δ‐unsaturated cycloalkanones. The yield of the two‐carbon ring‐expanded ketones greatly depended on the relative ring strains of substrate and product (5–87%, cf. Table 5). The formation of minor amounts of one‐carbon ring‐expanded cycloalkenes (<10%) can be ascribed to a subsequent decarbonylation step. A reaction mechanism involving initial cleavage of the weakest single bond in the molecule has been established (cf. Scheme 6). Recombination within the generated diradical intermediate in terminal vinylogous position led to the observed products, while reclosure gave recovered starting material. Substituents on the vinyl moiety were transferred locospecifically into the ring‐expanded products. An isopropenyl group did not significantly affect the isomerization process, whereas substrates bearing a prop‐1‐enyl group in β‐position enabled competing intramolecular H‐abstraction reactions, leading to acyclic dienones (cf. Schemes 9–11). DGPTI of the 13‐membered analogue directly yielded 4‐muscenone, which, upon hydrogenation, led to the valuable musk odorant (±)‐muscone. Increasing the steric hindrance on the vinyl moiety gave rise to diminishing amounts of the desired γ,δ‐unsaturated cycloalkanones. This novel two‐carbon ring‐expansion protocol was also successfully applied to 3‐ethynylcycloalkanones, giving rise to the corresponding ring‐expanded cyclic allenes (cf. Scheme 13).