Aminations enones

The direct photocyclization of another interesting acceptor-donor pair, the amine-enone system, has been reported by Mariano [224-226]. Direct irradiation of -(aminoethyl)cyclohexenones 281 leads to the excitation of the conjugated cyclohexenone chromophore. Intramolecular single-electron transfer from the amine donor to the cyclohexenone excited state results in the formation... 

U. C. Yoon u. P.S. Mariano, Acc. Chem. Res. 25, 233-240 (1992) . .Mechanistic and Synthetic Aspects of Amine-Enone Single Electron Transfer Photochemistry". 

The results of these studies were compared with those obtained earlier for the stilbene amine photoaddition [7, 11] and amine-enone photoelectron-transfer-catalyzed cyclizations (Table 7). The effects of a-substituents on the a-CH deprotonation rates of aminium radicals measured in the stilbene-amine photoaddition... 

Analogous to DPNH (144-146), 1,4-dihydropyridines (147) act as reducing agents. For instance, the conversion of aromatic nitro compounds to amines (148) and reduction of enones to ketones (749) has been achieved. 

A seven-membered fused ring system 66 (85-95%) has been built by variation of the amine component. Tliis example deals with the reaction of 33 with 3-(2-aminophenyl)amino-5,5-dimethylcyclohex-2-enone (65)... 

The net effect of the Stork reaction is the Michael addition of a ketone to an cn/3-unsaturated carbonyl compound. For example, cyclohexanone reacts with the. cyclic amine pyrrolidine to yield an enamine further reaction with an enone such as 3-buten-2-one yields a Michael adduct and aqueous hydrolysis completes the sequence to provide a 1,5-diketone (Figure 23.8). 

The amine-catalyzed Diels-Alder dimerization reaction of a, 3-unsaturated ketones in water was developed by Barbas et al. to form cyclohexanone derivatives (Eq. 12.12). They believe that the reaction proceeds via the in situ formation of 2-amino-1,3-butadiene and iminium-activated enone, as the diene and dienophile, respectively. 

Similarly, the addition of an amine to the enone moiety can initiate a domino process leading to substituted diaminocyclohexanes [34]. In this transformation an imino aldol reaction occurs. The observed stereoselectivity was again >95 5, and the yield between 51 % and 69% in all cases. 

Yamamoto s group recently published a highly enantioselective chiral amine-catalyzed domino O-nitroso aldol/Michael reaction of 2-268 and 2-269 (Scheme 2.63) [141]. As products, the formal Diels-Alder adducts 2-271 were obtained with >98% 66, which is probably due to the selective attack of an enamine, temporarily formed from amine 2-270 and enone 2-268, onto the nitroso functionality. 

In order to explore the generality of this new domino reaction the conversion of various primary amines with 2-341 and the cyclohexane analogue was investigated (Scheme 2.81). For example, the reaction proceeds with high yields when benzyl- or (2-phenylethyl)amine are used (entries 1 and 2). In comparison, sterically more hindered amines such as 2-butylamine produced much lower yield (entry 4) Furthermore, the reaction tolerates other functional groups, such as an unprotected hydroxyl group (entry 5), and variation of the enone ring size is possible (entries 6 and 7). More recent results have revealed that the addition of Sn(OTf)2 or In(OTf)2 makes the transformation more reliable. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

A series of 3-oxothiophene derivatives has been prepared by intramolecular thia-anti-Michael addition of a thiol anion to an enone functionality, resulting for instance in preparation of the target 20 by treatment of the precursor 21 with an amine <06JOC8006>. 

CF3-Enones 131 showed different reactivity in amination reactions to nosyloxycarbamates. In particular, 4-oxazolines 133 were synthesized operating in the... 

A similar strategy has been used for the Biginelli condensation reaction to synthesize a set of pyrimidinones (65-95%) in a household MW oven [152]. This MW approach has been successfully applied to combinatorial synthesis [153]. Yet another example is the convenient synthesis of pyrroles (60-72 %) on silica gel using readily available enones, amines and nitro compounds [154]. 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Dieter developed a flexible two step synthesis of substituted pyrroles involving initial Beak deprotonation of /ert-butoxycarbonyl (Boc) amines 36 followed by addition of CuX-2LiCl (X = -Cl, -CN) to afford a-aminoalkylcuprates. Such cuprates undergo conjugate addition reactions to a,(3-alkynyl ketones affording a,(3-enones 37, which upon treatment with PhOH/TMSCl undergo carbamate deprotection and intramolecular cyclization to afford the pyrroles 38 . 

The isoxazoles 184a and b were synthesized by Selvam et al., and the synthesis is described in Scheme 50 [87]. As with Scheme 49, this group utilized hydroxyl amine reacted with the /1-hydroxy enones (169 and 185) to form the isoxazoles (184a and b). 

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