Intramolecular oxa-Michael reaction

Scheme 4.62 Enantioselective intramolecular oxa-Michael reactions for the synthesis of chromanes.

Scheme 4.63 Enantioselective intramolecular oxa-Michael reaction for the synthesis of chromanones and flavanones.

The synthesis of the as-fused butyrolactone tetrahydropyran core of (-b)-Greek tobacco lactone involves an intramolecular oxa-Michael reaction of a furan-3-en-2-one bearing a propanediol chain at C-5 (14SL1888). Prins cyclization of ( /Z)-6-mercaptohex-3-en-l-ol with aliphatic and aromatic aldehydes is condition-controlled stoichiometric amounts of strong Lewis or Bronsted acids afford mainly thiophen[c]-fused tetrahydropyrans whereas catalytic amounts of weak Lewis or Bronsted acids provide furan[c]-fiised tetrahydrothiopyrans as major products (Scheme 13)... 

Intramolecular oxa-Michael reaction of 2 -hydroxychalcones promoted by an organocatalyst based on aminoquinoline and pyrrolidine leads to 2-aryl-4ff-chroman-4-ones, in good yields with high enantioselectivity (14TL3255). A wide range of 3-aryl-4H-chroman-4-ones are readily... 

Scheme 15.27 Highly enantioselective intramolecular oxa-Michael reaction of alkojg boronate employing squaramide eatalyst.

Recendy, we described a useful sequence where Michael-acceptor sulfoxides 30 were obtained in two steps from homopropargylic alcohols 29 by radical addition of thiophenol and oxidation with sodium periodate. The unsaturated sulfoxides were used in a highly stereoselective intramolecular oxa-Michael reaction. The sequence provided stereoselective functionalization of the sulfoxide moiety, and the products 31 proved to be useful in the synthesis of modified furanosides 32. This represents a good exanple where sugars are prepared from acyclic precursors. The Michael addition was followed by a hydrolytic Pummerer reaction, yielding protected a-hydroxy aldehydes tScheme 20.8) that upon acidic treatment afforded 3-substituted ribofuranoses. 

The synthesis of unique seven-membered ring sultams has been reported, by an intramolecular oxa-Michael addition reaction from vinyl sulfonamides 248 via a one-step or two-step method, both of which give similar yields of sultams, 249 (13T2369).The intramolecular oxa-Michael reaction was initiated by either TBS-deprotection (with TBAF) to form alkoxide intermediates (Method A), or by removal of the protecting group by HCl to give vinyl sulfonamide alcohols which, upon reaction with NaH, the oxa-Michael reaction is initiated (Method B). 

Alternatively, a ruthenium catalyst could be applied in phthalide preparation. In 2011, Ackermann s group developed a ruthenium-catalyzed cross-dehydrogenative C-H bond alkenylation reaction. The methodology used water as a solvent, benzoic acids and terminal alkenes as substrates good yields of the desired phthalides were isolated (Scheme 2.164). The reaction sequence consisted of cross-dehydrogenative alkenylation and a subsequent intramolecular oxa-Michael reaction. Mechanistic studies provided strong evidence that the oxidative alkenylation proceeds by an irreversible C-H bond metalation via acetate assistance. 

In 2011, Ackermann and Pospech [67] reported the Ru-catalyzed C-H bond activation on aromatic acids with olefins to give cyclic phthalides (Figure 4.33). What was notable about this procedure was that it showed very good functional group tolerance, scope, and yields, not to mention that it was conducted in water. The reaction mechanism involves a cross-dehydrogenative alkenylation and subsequent intramolecular oxa-Michael reaction. 

Based on the concept of tandem reaction, a series of synthetic routes have been developed, including an intramolecular Aldol/Oxa-Michael/Aldol/Lactonization synthetic strategy (see Fig. 1.17). The retrosynthetic analysis indicated that the synthesis starts from compound 1.7.21, which first undergoes an intramolecular Aldol reaction then immediately intramolecular Oxa-Michael reaction to form the tricyclic system. Finally through the intermolecular Aldol reaction and intramolecular esterification reaction, the tetracyclic skeleton of Maoecrystal V can be constructed. And 1.7.21 can be provided by the relatively simple materials 1.7.22 and 1.7.23 through Suzuki cross-coupling reaction. 

Oxa-bridge/IMDA Strategy Intramolecular Oxa-Michael Reaction... 

Vicinal diamines (ent-247) and (249) have been shown to catalyse the intramolecular oxa-Michael reaction of (277) via iminium activation, affording 1,4-dioxanes (278) with <98% ee ... 

After the seminal work reported by Satoh and Miura in early 2011 on ruthenium-catalyzed oxidative vinylation of heteroarene carboxylic acids with alkenes [17], Ackermann demonstrated a ruthenium(ll)-catalyzed cross-dehydrogenative C-H bond alkenylations of benzoic acid derivatives with acrylonitrile or alkyl acrylates. Following the oxidative C—H bond alkenylation reaction, subsequent intramolecular oxa-Michael reaction occurred leading to phthalides in good yields (Eq. (7.12)) [18]. The reactions took place with water as an environmentally benign medium under mild conditions. 

In 2007, Scheidt reported an intramolecular oxa-Michael reaction of a-substituted chalcones 114 catalyzed by cinchona alkaloid derived thiourea 113. Chromanones 115 were efficiently produced after an acid-promoted decarboxylation process (Scheme 36.31) [39a]. 

An alternative access to C-glycosides is given by Wittig or Horner olefina-tion of unprotected carbohydrates with the corresponding phosphonate. Subsequent intramolecular oxa-Michael reaction gives an access to glycoside 8 of acetone. A big excess of base is necessary for the reaction (see the example of xylose in Eq. 3 Scheme 2.1) [7],... 

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