Baylis-Hillman reaction Subject

Jauch achieved the short and elegant total synthesis of mniopetals during almost the same period in which our total syntheses were reported [36-41]. We briefly introduce Jauch s achievements on this subject. The key step of his synthesis was the IMDA reaction of 2-substituted butenolide 124 (Scheme 20), which was prepared by the diastereoselective PhSeLi-induced Baylis-Hillman reaction of 122 and Feringa s butenolide 123 [99]. The cycloadduct of this IMDA reaction 125 was transformed into kuehneromycin A and mniopetals E and F, respectively. 

Genisson et al. also prepared two diastereomers of 2 -hydroxymethyl analogs through an asymmetric Baylis-Hillman reaction-like sequence to prepare a A-substimted 2 -methylene C-13 side chain (Scheme 3-3). After incorporation of the side chain to C-13 of 7,10-ii/-Troc-10-DAB, the product was then subjected to osmylation to yield 2 (R)- and 2 (5)-hydroxymethyl docetaxel 7a-b analogs stereoselectively. Both taxoids displayed less tubulin polymerization abilities than did paclitaxel, but the major product 2 / -isomer 7a is more active than the minor one 2 5-isomer 7b. ... 

In order to access isoxazole-based potential antithrombotic agents [409], acrylic acid was loaded onto 2-chlorotrityl resin and then subjected to Baylis-Hillman reaction -with a variety of 3-substituted phenyl-5-isoxazolecarboxaldehydes (pre-... 

Benzpyloxymethyl-2-alkenoic esters. These esters are formed when the Baylis-Hillman reaction products are subjected to the reaction of Pl P-DEAD and a carboxylic acid. An Sj 2 pathway is followed. The addition of EtjN is beneficial, because it undergoes quatemization. Thus, the subsequent displacement by the carboxylate ion affords much more rearranged (S 2 ) products. 

Barrett and Kamimura have developed a stepwise asymmetric catalytic variant of the Baylis-Hillman reaction. A stoichiometric amoimt of nucleophile, MesSi-SPh or MesSi-SePh (7.174) is added, but only a catalytic amount of Lewis acid (7.175) in the reaction between methyl vinyl ketone (7.168) and acetaldehyde (7.176). The aldol adduct (7.177) was subjected to oxidation and selenoxide elimination to give the product (7.178), which is the same as the product from a Baylis-Hillman reaction. 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

The basic nature of N-heterocyclic carbenes, stabilized by the presence of two adjacent N atoms, has been emphasized by several authors [38], Therefore, the yield and the selectivity of any organic synthesis (driven by the reactivity of a substrate vs. appropriate bases and carried out in imidazohum salts as solvents) can be affected by side reactions related to the acidity of C2-H unit in 1,3-dialkylimidazo-lium cation and to the basicity and nucleophilicity of the resulting N-heterocychc carbene. On this subject, noticeable work (related to the Baylis-Hillman, Knoevenagel and Claisen condensation, Homer reaction, etc.) carried out in RTlLs has been reported and discussed [37]. 

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