Alkylidene lactams, from

A one-pot cascade approach to 4-alkylidene-(3-lactams from aryl azides and aryloxyacetyl chlorides has been reported. (4-Methyloxyphenyl)azides reacted with triphenylphosphine in 1,2-dichloroethane to form triphenylphosphazene, which was treated with phenoxyacetyl chloride and Et3N to afford 4-phenoxy-methylene-(3-lactam (Scheme 45), [122]. 

Insertion into Si-H bonds. a-Silyl esters are similarly obtained. From R2Si(Cl)H the products are readily converted into o-(alkoxysilyl)alkanoic esters. Heterocyclization. Formation of a-alkylidene lactams by carbonylation of alkynyl amines and cyclization of 2-allyloxybenzylamines with allylic rearrangement are reported. 

Nay B, Riache N, Evanno L. Chemistry and biology of non-tetramic y-hydroxy-y-lactams and y-alkylidene-y-lactams from natural sources. Nat. Prod. Rep. 2009 26 1044-1062. 

Stang etal. (94JA93) have developed another alkynyliodonium salt mediated approach for the synthesis of y-lactams including bicyclic systems containing the pyrrole moiety. This method is based on the formation of 2-cyclopentenones 114 via intramolecular 1,5-carbon-hydrogen insertion reactions of [/3-(p-toluenesulfonyl)alkylidene]carbenes 113 derived from Michael addition of sodium p-toluenesulfinate to /3-ketoethynyl(phenyl) iodonium triflates 112 (Scheme 32). Replacing 112 by j8-amidoethynyl (phenyl)iodonium triflates 115-119 provides various y-lactams as outlined in Eqs. (26)-(30). 

The most reactive Michael acceptors, such as alkylidene malonates, gem-dicyanoalkenes and nitroalkenes, react with a-halozinc esters in a conjugate fashion. Beautiful examples were offered by two stereocontrolled conjugate additions to piperidinone 102 and pyrro-lidinone 104 leading to optically active bicyclic lactams 103147 (equation 60) and 105 (equation 61)148. With these electron-poor alkenes a Grignard two-step protocol is to be adopted in order to avoid the single electron transfer reactions from the metal to the Michael acceptor, which should afford olefin dimers. The best solvent is found to be a... 

Cainelli and coworkers have reported in 2006, some further advances in the preparation of 4-alkyliden-(3-lactams starting from 4-acetoxy azetidinones and diazoesters [294]. 

Chiral alkoxy allenes derived from 1,3-alkylidene-L-erythritol and -D-threitol have been used in cycloaddition reactions to provide the 4-substituted /3-lactams 418 (R = Me, Ph). Intramolecular alkylation at nitrogen was achieved by the action of potassium carbonate and tetrabutylammonium bromide in dry acetonitrile. The absolute stereochemistry of the product 419 (R = Me, Ph) was assigned on the basis of the CD helicity rule (see Section 2.04.3.5) and NMR spectroscopy. The [2+2] cycloaddition of CSI to threitol vinyl ethers was found to have low stereoselectivity in contrast to the findings with erythritol derivatives <2004CH414, 2005EJ0429>. 

Several other transannular lactonizations and reductions have been reported to proceed in high overall yields. Also other acid derivatives, such as amides and esters, cyclize to form lactones. Alkynoic acids have been lactonized to y-alkylidene-y-lactones in good yield, e.g. the conversion of (31) to (32 equation 29). Unfortunately the vinyl selenide product can isomerize from ( ) to (Z) in a secondary process. Analogous lactam formation is also known. Unsaturated amides, when cyclized with benzenese-lenenyl halides, produce good yields of lactams or iminolactones depending upon the alkene utilized. The amide (33) cyclizes to the iminolactone (34), producing a mixture of stereoisomers (65 35 Scheme 5). The amide (35) is cyclized to lactam (36) in moderate yield. 

A series of alkenes 20, derived from amino acids, react with the dienol 21a to give adducts 22. Formation of the additional lactone and lactam rings occurs prior to isolation of the product. A complete facial selectivity, but only moderate (22a) to low (22b and 22c) yields are obtained9. To prevent lactone ring formation several protected derivatives of dienol 21 were reacted with alkylidene malonic ester 20a. Only diene 21g reacts in an acceptable yield and selectivity10. 

C. From Rings with an Endocyclic Keto Group Adjacent to an Exocyclic Ester, Ketone, or Methide (Alkylidene) Substituent or from Lactones or Lactams... 

Similarly, y-lactams are prepared from 2-alkynamides bearing an allyl acetate moiety on nitrogen. The last step is deacetoxypadladation to generate Pd(II) [153], The a-alkylidene-y-butyrolactam 388 was obtained by cyclization of the A -allylic 2-alkynamide 387 using Pd(OAc)2 and LiBr, and the reaction has been applied to the synthesis of isocynometrine (389) [154], The aldehyde 392 was obtained by cyclization of the alkynic a -unsaturated aldehyde 390, followed by protonolysis of the insertion product 391 with AcOH [155],... 

EtAlCl2). The reaction is highly diastereoselectlve at C(8) and selectivity for formation of (E)-alkylidene products increases with the size of the R substituent as would be expected from a concerted mechanism involving an AlCl complex of (297) H transfer occurs from a conformation in which the R substituent of (297) occupies the least hindered position. Two useful additions to acyliminium ion cyclization methodology have appeared. Firstly, hydroxy-lactams (299) can be cyclized in excellent yields to the exomethylene cyclic lactams (300) by using an allyl-silane as the 192... 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

In 2006, Janecki et al [67] reported that when 2-diethoxyphosphoryl-4-oxoaUcanoates 137 are treated with primary amines, such as benzylamine and hexylamine, the formation of y-alkylidene-a-diethoxyphosphoryl-y-lactams 140 as the only products is observed (Scheme 4.37). 2-Diethoxyphosphoryl-4-aminoalkanoates 139 necessary for the cyclization reaction were formed from the initially formed imines 138 via imine-enamine tautomerization. Interestingly, the reaction sequence proceeded in a highly stereoselective manner as E-configured products (EfZ >95 5) predominated in the reaction mixtures. Subsequent HWE olefination of formaldehyde with phosphonates 140 yielded y-alkylidene-a-methylene-y-Iactams 141 in moderate to good yields with unchanged E/Z ratio with respect to the starting phosphonates 140. 

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