Michael addition internal

Dien)olones, Michael addition, internal, of — 16, 758 Dienones... 

ISOC reaction was employed to synthesize substituted tetrahydrofurans 172 fused to isoxazolines (Scheme 21) [44b]. The silyl nitronates 170 resulted via the nitro ethers 169 from base-mediated Michael addition of allyl alcohols 168 to nitro olefins 167. Cycloaddition of 170 followed by elimination of silanol provided 172. Reactions were conducted in stepwise and one-pot tandem fashion (see Table 16). A terminal olefinic Me substituent increased the rate of cycloaddition (Entry 3), while an internal olefinic Me substituent decreased it (Entry 4). 

By contrast, L-phenylalanine methyl ester does not react with BENA generated from 1-nitropropane (R =H) due apparently to low nucleophilicity of the amino group. However, the N, C -coupling reaction of the ester of this amino acid with another internal BENA (R = CC>2Me) proceeds rather readily but is characterized by extremely low diastereoselectivity. Probably, the last N,C-coupling does not occur via an intermediate a-nitroso alkene but by a classical Michael addition to BENA MeCH=C(C02Me)N(05i )2 as to Michael substrate. 

At 673 K the product distribution over the palladium catalysts (Figure 4) was still highly selective to MIBK (> 80%) however further aldol condensation of acetone with MO to form the three intermediates, phorone, 4,4 -dimethyl hepta-2,6-dione and 2,4-dimethyl hept-2,4-dien-6-one was observed. These species were formed by aldol condensation of acetone with MO at different points in the molecule (10). All can continue to react either by subsequent aldol condensation, Michael addition, or hydrogenation as per Figure 1. There was no detectable isophorone produced, the product of internal 1,6-aldol reaction of... 

It Is of Interest to note that the preparation of dimethyldihydroresorcinol (also named dimed one and methone Section VII, 15) Involves an initial Michael addition to mesityl oxide, followed by an internal Claisen condensation. 

The heterobimetallic multifunctional complexes LnSB developed by Shibasaki and Sasai described above are excellent catalysts for the Michael addition of thiols [40]. Thus, phenyl-methanethiol reacted with cycloalkenones in the presence of (R)-LSB (LaNa3tris(binaphthox-ide)) (10 mol %) in toluene-THF (60 1) at -40°C, to give the adduct with up to 90% ee. A proposed catalytic cycle for this reaction is shown in Figure 8D.9. Because the multifunctional catalyst still has the internal naphthol proton after deprotonation of the thiol (bold-H in I and II), this acidic proton in the chiral environment can serve as the source of asymmetric protonation of the intermediary enolate, which is coordinated to the catalyst II. In fact, the Michael addition of 4-/en-butylbenzcnethiol to ethyl thiomethacrylate afforded the product with up to 93% ee using (R)-SmSB as catalyst. The catalyst loading could be reduced to 2 mol % without affecting enantioselectivity of the reaction. 

Irie and co-workers (37) have recently observed that the double Michael reaction of dimethyl acetone dicarboxylate on dienone 104 gave the cis decal-in product 106. This result indicates that intermediate 105 underwent a stereoelectronically controlled internal Michael addition to give 106. Without stereoelectronic control in the Michael reaction, there is no apparent reason to prevent the formation of the trans isomer 107. However, if this factor is taken into consideration, examination of molecular models indicates that it seems impossible to obtain isomer 107. 

After Michael addition of 17 to 2-methyl-1,3-cyclohexanedione (19) and the first aldol condensation, the double bond in 20 is reduced to give 21. The acetoxy group in 21 is unmasked by hydrolysis and oxidation, and subsequent aldol condensation gives 22. Again, the terminal double bond in 22 is oxidized with PdCk to methyl ketone, and subsequent hydrogenation of the internal double bond affords the trione 23, from which the steroid A-ring 24 is formed by aldol condensation [34],... 

An oxidatively induced ring closure occurs during the oxidation of various catecholamines (33)72 at a carbon paste electrode. Whereas the oxidation in 1 M H2SO4 yielded the 1,2-benzoquinone (34), sufficient free amine of 34 was present at pH 3 to allow an internal Michael addition of the adrenaline quinone. As would be expected, the resulting catechol (35) is more easily oxidizable than adrenaline and is converted into the quinone adrenochrome (36) by chemical oxidation by adrenaline quinone. 

Reaction of benzylaminouracil with DAD affords xanthines via a Michael addition and internal disproportionation reaction [75CC146 77JCS(P1 )1754]. The Michael adduct of 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD) is easily converted into xanthines on heating with aromatic aldehydes [74CC551 77JCS(P1)2285]. Insoferevenulin can be pre-... 

With fluoride ion under aprotic conditions alkylating ring-opening can be performed (equation 94). Similarly, a clever [3 -I- 2] annulation combines a fluoride-induced Michael addition to vinyl phosphonium salts with a subsequent internal Wittig reaction (equation 95) . ... 

Addition of the a,3-unsaturated anion (21) to the Michael acceptor (22), in which either alkylation or 1,4-addition is possible, affords only the Michael product. Internal alkylation of the interme ate ester enolates leads to cyclopropyl derivatives (equation 7). Terpenoid polyenes are prepared through conjugate addition of the lithiat protected cyanohydrins (23) to dienyl sulfoxide (24 equation 8). ... 

The important intermediate 66 of the steroid synthesis has been prepared by the application of the same reaction sequence to 2-methyl-1,3-cyclohexanedione (65) (Scheme 22). A synthesis of (+) 19-nortestosterone (69) starts with the Michael addition of the optically active oxo ester 67 to 1,7-octadien-3-one (59) catalyzed by sodium hydride, the ester group being removed by heating in aqueous HMPA with sodium iodide to give the dione 68. The aldol condensation catalyzed by sodium hydroxide proceeds in 90% yield. The terminal double bond is oxidized with PdCl2/CuCl to the methyl ketone and the internal olefinic double bond subsequently hydrogenated. The final reaction step involves aldol condensation in refluxing... 

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