Substitution effect enone formation

As with 1-substituted glycals, 2-substituted glycals are known to be useful substrates for C-glycosidations. In these cases, the final products are enones. As shown in Scheme 2.3.41, Ferrier, etal.,67 demonstrated the utility of these reactions by effecting the formation of a 75% yield of the product shown. The reaction proceeded utilizing borontrifluoride etherate as a catalyst and displayed a preference for the a anomer. The specific reaction was successfully used in the preparation of trichothecene-related compounds. 

In an attempt to determine whether peracid oxidation of cyclopropenes to enones proceeds by ct- or ic-bond oxidation, Friedrich and Fiato compared the second-order rate constant for allylically substituted cyclopropenes and cyclopentenes. The results (Table 1) indicate rather small allylic substitution effects in the cyclopentenes, but larger rate reductions in the cyclopropenes. The magnitude of the effect is not in line with an epoxidation-type transition state and may be more consistent with o attack, but insufficient background data are available to allow firm conclusions from these results. A comparison of oxidation rates of 1,2-diphenyl-cyclopropene, -cyclobutene, and -cyclopentene yielded data which were much more consistent with oxabicyclobutane formation, as did an examination of substituent effects at the vinylic positions in cyclopropene. ... 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

Kinetic resolution is operative in the reaction with 4-substituted cyclopent-2-en-l-ones. For instance, when 2 equiv. of racemic 4-(l-methyl-l-phenylethoxy)-2-cyclopentenone (79) is reacted with the carb-anion (78), (5)-(79) reacts to yield predominantly the product derived by approach of the carbanion from the si face of (79). The formation of the cis adduct probably results from the chelation of lithium counterion with the C-4 oxygen (equation 22). Kinetically selective resolution of a bicyclic enone (80) is also effected. On treatment of the carbanion of (/ )-(78) with racemic (80) (2 equiv.), an enantiomer of (82) and (5)-(80) are obtained in 80% and 45% yields respectively. Addition of the lithio derivative (2 equiv.) of... 

The dienophile may also be activated by hydrogen bonding of the carbonyl oxygen with suitable protic molecules and it has been observed that Diels-Alder reactions are accelerated when performed in protic solvents such as 2-butanol. Thus the opportunity exists for the development of an enantioselective alcohol-catalysed asymmetric Diels-Alder reaction. Indeed, Rawal and coworkers have recently discovered that the use of catalytic amounts of the enantiomerically pure diol a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) (8.113) in the Diels-Alder reaction of aminosilyloxydiene (8.114) with 2-substituted acroleins such as (8.24), results in the formation of the cycloadduct (8.115) with high ee. Simiharly, the strong Bronsted acid (8.116) effectively catalyses the Diels-Alder reaction of sUyloxydienes such as (8.117) with a,P-enone (8.105). ... 

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