Methylene groups, activated Michael-type addition

Approaches of type (i) include the Michael type addition of ester activated methylene groups to a,( -unsaturated carbonyls with subsequent cyclization to afford 277-pyran-2-ones <1984CHEC, 1996CHEC-II>. In this manner, 3-acylamino-277-pyran-2-ones are prepared by the reaction of (3-ethoxyvinyl ketones or P-(dimethylamino)vinyl ketones with iV-acylglycines (Scheme 138) <2005S1269, 2004HAC85>. 

Fillipone reported a solid phase synthesis of pyrroles from 1,2-diaza-1,3-butadienes 43 and 3-ketoamides 44 in the presence of copper(II) dichloride <01T5855>. It is envisaged that Michael-type addition of the activated methylene on the 1,2-diazaheterodiene moiety is followed by an intramolecular addition of the nitrogen atom of the C=N group to the carbonyl in 5-position yielding the pyrroles 45. 

Formation of the 1 1 or 1 2 adducts is determined by the structure of the Michael acceptor. The presence of substituents on the a-carbon at the double bond favors almost exclusive formation of the 1 1 adduct. To a lesser extent, the product ratio depends both on the reactant ratio and on the amount of base. By a careful choice of conditions, either compound can be favored. The addition of a-substituted compounds containing active methylene groups to acrylonitrile or methacrylonitrile gives 1 1 Michael-type adducts. The yields are fair to good in the first case and rather modest in the second. 

Barbituric acids have been employed as the active methylene compounds in the Michael addition to 4-vhiylpyridine to yield the barbiturates XI-33. A variety of 3-vinylpyridyl ketones of the type XI-34 were treated with esters containing active methylene groups to form the 6-keto esters (XI-35). ... 

The formal addition of a C-H bond at activated methylenes and methynes (pronucleophiles) to activated alkenes in the presence of a base is well known as the Michael reaction (Scheme 1, Type A) [1]. In modem organic syntheses, the use of transition metal (TM) catalysts enables the C-H addition of activated methylenes and methynes to activated alkenes perfectly under neutral conditions (Scheme 1, Type B) [2]. In general, the nonfunctionalized carbon-carbon multiple bonds (for example, EWG2 = H in Scheme 1) are unreactive toward carbon nucleophiles because of their electron rich Jt-orbitals. The pioneering efforts by various research groups resulted in the development of transition metal-catalyzed addition of a C-H bond at active alkanes to such unactivated C-C multiple bonds. This reaction consists of the formal addition of a C-H bond across the C-C multiple bonds and is called a hydrocarbonation reaction. As a milestone in this hydro-carbonation area, early in the 1970s, Takahashi et al. reported the Pd-catalyzed addition of the C-H bond of pronucleophiles to 1,3-dienes [3], The first Pd-catalyzed reaction of activated methylenes with unsubstituted allenes was apparently reported by Coulson [4]. The synthetic applications of this reaction were very limited. In the last decade, the Pd-catalyzed addition of C-H bonds to various unacti-... 

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