Regio‐ and Diastereoselective Conjugate Addition to 4,4‐Dimethylcyclohexadienones

Abstract

Conjugate addition of vinyl cuprate and dimethyl malonate to 4,4‐dimethylcyclohexa‐2,5‐dienones has allowed facile access to mono‐ and bis‐adducts in satisfactory yields. While the high diastereoselectivity of such processes to afford trans‐bis‐adducts was predictable, an unprecedented regioselectivity was observed with 2,4,4‐trimethylcyclohexa‐2,5‐dienone, with the first addition occurring exclusively at the C‐5 carbon atom (distal from the methyl group) and with the second addition of a bulky nucleophile such as dimethyl malonate even prevented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Regioselective and stereoselective cyclizations of cyclohexadienones tethered to active methylene groups

“…This is in agreement with an observation made by Giomi and coworkers concerning the addition of diethyl malonate to an orthomethyl-substituted dienone. 22 Higher regioselectivity (12 : 1) was observed in the cyclization of 4l to 9l, where the methyl group is in the b position. This dependence could easily be attributed to steric effects; however, an electronic argument involving the weakly electron-donating nature of methyl substituents should not be discounted.…”

“…This was initially accomplished with a trifluoroacetic anhydride-mediated coupling of the tertiary alcohol with the malonic acid monoester; 13 however, the use of DCC was later found to be more convenient and cost effective, particularly on larger scales. These reactions are applicable to a wide range of substrates (Table 1), including those with sterically demanding R 3 substituents (entries 7,9,11,22,23). Malonates with orthogonal protecting groups are tolerated (entries 1, 2, 3) as well as other electron-withdrawing groups such as amides (entry 4) and sulfones (entry 5).…”

Unusual Ring Opening of Bicyclic Terpenes During Pd‐Catalyzed Coupling with Aromatic Halides

“…[22] Numerous functional groups can be inserted into the 2-position of 4,4dimethylcyclohexa-2,5-dienone by methods of transition metal catalysis. [29] Moreover, related derivatives of 4,4-dimethylcyclohexa-2,5-dienone are used as dienophiles in Diels-Alder reactions, [30][31][32] form Michael adducts with various C-nucleophiles, [33][34][35] form anionic radicals under the action of reducing agents [36,37] and can undergo aromatization with the formation of substituted derivatives of o-xylene due to dienonephenol type rearrangement. [38,39] Having summarized numerous perspectives, we began to study the discovered reaction and its mechanism.…”