Cyclohexenone analogues

From the facts that on irradiation of the same thiinone in furan/methanol only the furan cycloadducts are formed, and that the formation of these cycloadducts is quenched on addition of -stilbene, it was stated [58] that the thiinone represents the first monocyclic cyclohexenone analogue undergoing... 

Unsaturated lactone 74 (Scheme 7.21) can be viewed as an oxygen heterocyclic analogue of 2-cyclohexenone, and it has recently been reported that catalytic 1,4-additions of Et2Zn to 74 can indeed be accomplished with high enantioselectivity. For adduct 76, Reetz achieved a remarkable 98% ee when employing ferrocene-based diphosphonate ligand 23 [48]. Using diphosphite 24, Chan et al. achieved an ee of 92% for the six-membered lactone 74 and a 56% ee for the five-membered lactone 25 [49c]. 

The intrinsic basicities of cyclopentenone and cyclohexenone (59), and their lactone analogues (60), have been accessed via measurement of their gas-phase proton affinities, and compared with the saturated carbonyl compounds in both cases. The results... 

Cyclohexanediamine-derived amine thiourea 70, which provided high enantio-selectivities for the Michael addition [77] and aza-Henry reactions [78], showed poor activity in the MBH reaction. This fact is not surprising when one considers that a chiral urea catalyst functions by fundamentally different stereoinduction mechanisms in the MBH reaction, and in the activation of related imine substrates in Mannich or Streclcer reactions [80]. In contrast, the binaph-thylamine thiourea 71 mediated the addition of dihydrocinnamaldehyde 74 to cyclohexenone 75 in high yield (83%) and enantioselectivity (71% ee) (Table 5.6, entry 2) [79]. The more bulky diethyl analogue 72 displayed similar enantioselectivity (73% ee) while affording a lower yield (56%, entry 3). Catalyst 73 showed only low catalytic activity in the MBH reaction (18%, entry 4). 

Synthetic work on the mesembrane group will no doubt be further stimulated by reports on their central nervous system activity and somewhat surprising biosynthesis. An interesting asymmetric synthesis of unnatural (+ )-mesembrine (38) has been announced (Scheme 4). The key intermediate (35), prepared in nine steps from 1,2-dimethoxybenzene, was treated with L-proline pyrrolidide (36) under conditions typical for the preparation of enamines. The product was not isolated but subjected to reaction with methyl vinyl ketone followed by acid treatment to give the cyclohexenone (37) in 38 % overall yield. The last step in the synthesis [(37) — (38)] was based on previous synthetic work on mesembrine alkaloids. The synthetic (+ )-mesembrine (38) was shown to exhibit a positive Cotton effect and thus an antipodal relationship to natural (— )-mesembrine. The mesembrine analogues (40 = H or OMe, = H, Me, or CHjPh) have... 

Elaboration of simple "aglycones" has led to the thiophene analogue (71) of the antiviral compound pyrazofurln and, from 2,5-anhydro-3, -0-lsopropylldene-D-arablnose, the splro-compound (72) and the cyclohexenone (73) by use of pentan-2,5-dlone and... 

The proposed reaction mechanism involves initially the activation of cyclohexenone by the thiourea group and subsequently a Michael addition of the tertiary amine at the p-position. The resulting enolate intermediate attacks the aldehyde performing an aldol reaction. Finally, a retro-Michael addition releases the catalyst to afford the product (Scheme 19.22). This mechanism supports the experimental results of the authors diethyl analogue 16b showed similar enantioselectivities, but significant lower yield for the reaction between 2-cyclohexen-l-one and 3-phenylpropionaldehyde, presumably because of the difficulty of the amine to perform the Michael addition due to confined space in the presence of the more flexible ethyl substituents. 

In 2007, Tsuji and co-workers showed NHC-Rh complexes 107 with dendrimer substituents were more active than Rh analogues in the hydrosilylation of 2-cyclohexenone (Figure 13.18). Furthermore, 107 gave the 1,4-adduct as major product, whereas Rh complexes 100 led preferentially to the 1,2-adduct instead. Alternatively, related complex 108 was fairly elfective for the hydrosilylation of ketones with diphenylsilane to give the corresponding alcohols in moderate to good yields (67-93... 

Reactions.—Various cyclohexenyl trimethylsilyl ethers react with a combination of 2,3-dichloro-5,6-dicyanoquinone (DDQ) and bis(trimethylsilyl)acetamide (BSA) to give the corresponding cyclohexenone [equation (39)] cyclopentenyl and cycloheptenyl analogues give lower yields. A combination of palladium(ii) acetate and p-benzoquinone will effect the same dehydrosilylation. ... 

Harding et aO have observed that acid treatment of cyclohexenone (186) results in cyclization to the tricyclic system (187), whereas, under the same conditions, cyclization of acetylenic analogue (188) halts at the bicyclic stage. 

Synthetic analogues have been prepared as exemplified in Scheme 14 [95]. A first Wittig-Homer olefination of aldehyde 107, followed by acidic treatment, generates cyclohexenone 108. Chemo- and stereoselective reduction of the latter with 9-BBN followed by sy -selective epoxidation of the allylic alcohol (lateral hydroxyl group control) by w-chloroperbenzoic acid gives 109. Selective tosylation of its secondary alcohol moiety (steric hindrance makes the tosylation of the tertiary alcoholic moiety difficult) and subsequent deprotonation of the tertiary alcohol with NaH provide an alcoholate that undergoes an intramolecular displacement reaction. 

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