A-Methylene-p-lactams

N-(n-Butyl)-a>methylene-p-lactam (2). CO was bubbled through Pd(OAc)a or Pd(Pt)3P)4 (0.136 mmol) in CHJCI2 (4 mL) After 2 nwi PhaP (0 54 mmoO CHjCIa (2 mL) is added tollowed by azindine 1 in CHaCIa After 40 h, the solvent was removed in vacuum and the residue porilied by prep tic (silica gel, hexane -EtOAc 8 1) to yield 2 (79%)... 

Lactams, a-Methylene-p-lactams can be prepared by carbonylation of 2-bromoallylamines catalyzed by Pd(OAc)2 or Pd(acac)2 and P(C6H5)3. ... 

A more conventional carbonylation route to -lactams involves the palladium-catalyzed conversion of various 2-bromo-3-aminopropene derivatives into the corresponding a-methylene-P-lactams (equation... 

Liebscher and Anklam [100] have introduced a facile access to novel optically active spiro-p-lactams 112-113,115-116 through cycloaddition reaction of diazomethane to a-alkylidene-p-lactams (Scheme 29). Diazomethane gave a clean reaction to a-methylene-p-lactam 111 affording spiroazetidin-2-ones 112, 113 (d.r. 87 13, 93%) with preference of anti-addition with respect to the CH2OTBS substituent. The a-ethylene-p-lactam 114 reacted slowly with diazomethane and... 

Electron-poor a-methylene-p-lactams were reported to undergo cross-metathesis more rapidly and efficiently than more electron-rich analogs. Significantly, tetrasubstituted alkenes have for the first time been accessed by cross-metathesis reactions (III, Fig. 27), [308]. 

Wassermann has reported (19—21) the synthesis of ( )-3-ANA by way of the P-lactam (25). Various methods were used to prepare (25), such as cyclopropane ring expansion of (24), cyclisation of (26) or acylation of the azetidine carboxylate (27). In another approach (22) the a-methylene P-lactam (28) has also been elaborated to 3-ANA via the use of (29). 

A new and facile synthesis of various 2[alkylamino(diethoxyphosphonyl)me-thyl] acrylic esters (335) has been developed. They constitute intermediates of choice to each a-methylene-p-functional azetidinones (336) through a tandem hydrolysis-intramolecular lactamization (Figure 53). °... 

A one-pot cascade approach to 4-alkylidene-p-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 EtsN to afford 4-phenoxy-methylene-p-lactam (Scheme 45), [122]. 

In a similar manner, simple Baylis-Hillman alcohols 62 were transformed into P,y-disubstituted-a-methylene-y-lactams 29b (Scheme 4.16) [48]. The sequential treatment of alcohols 62 with HBr, DABCO (l,4-diazabicyclo(2.2.2]octane), and a nitroalkane 51 afforded the requisite 2-methylene-4-nitroalkanoates 63 as two diastereoisomers in a 1 1 ratio. Subsequent standard transformations involving reduction of the nitro group and lactamization gave the final products 29b as mixtures of two diastereoisomers with the ratio originating from the substitution... 

Scheme 4.16 Synthesis of p,y-disubstituted-a-methylene-y-lactams 29b from Baylis-Hillman alcohols 62.

In Entry 11 the dienophile is an a-methylene lactam. As noted for this class of dienophiles, the stereoselectivity results from preferred exo addition (see p. 471). The reaction in Entry 12 was used in an enantiospecific synthesis of estrone. The dienophile was used in enantiomerically pure form and the dioxolane ring imparts a high facial selectivity to the dienophile. The reaction occurs through an endo TS. 

Debenzylation of Ar-benzyl-6e/a-lactams 41 has been achieved by electrooxidative methoxylation of 41 at the benzylic position followed by hydrolysis with p-toluene-sulfonic acid in acetone 27>. For example, the electrolysis of A-benzyl-3-methylene-6e/fl-lactam 41 (R = OMe) in an MeOH E NClC —fPt) system in an undivided cell forms iV-methoxybenzyl-3-methylene-6efa-lactam 42 (R = MeO) in 54% yield (Scheme 2-14). The debenzylation of 42 is carried out on treatment with p-toluene-sulfonic acid in aqueous acetone to give 3-methylene-6e/a-lactam 43 in 50% yield. 

P-Lactams. Carbon monoxide inserts into 2-bromo-3-aminopropene derivatives in the presence of a catalytic amount of Pd(OAc)2 and triphenylphosphine to give a-methylene- -lactams in 38-89% yield. Pd(acac)j can be used instead of Pd(OAc)2 with similar results. ... 

A highly efficient cyclization of 2-chloro-4-sulfonamino-l-alkenes to 2-methylene-azetidines provides an avenue to P-lactams, e.g., on ozonolysis of the products. Pertinent to cyclization of bromoallyl bromohomoallyl carbinols is the chemo/regioselectivity. It is actually dependent on the nature of the promoter, Cul or Pd(OAc)2. ... 

In continuation to this, they used a,p-unsaturated p-lactams 79 for the construction of spirocyclic compounds 80-82 (Scheme 21) by the addition of a methylene... 

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