Y-butyrolactams

Bode and co-workers have used NHCs to form y-butyrolactams 34 from enals 27 and saccharin-derived cyclic sulfonylimines 32. A range of [3-alkyl and [3-aryl substituted enals, and a variety of substituted imines, are tolerated in this reaction,... 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

Similarly, the N-Boc-protected 3,4-methano-y-aminobutyric acid 141 and the 4-spiro-cyclopropane-y-butyrolactam 145 have been obtained in overall yields of 55% and 44%, respectively (Scheme 11.36) [109,110,119b]. 

Beckmann like rearrangements have not been extensively explored but should translate this spiroannulation into a y-butyrolactam synthesis108). 

Mahboobi et al. described a novel synthesis of staurosporinone (293) (791). The intermolecular Michael addition of l-(indol-3-yl)-2-nitroethene (1472) to methyl indol-3-ylacetate (1313) provided with high diastereoselectivity methyl 2,3-bis(indol-3-yl)-4-nitrobutanoate (1473). Catalytic hydrogenation and lactamization afforded 2,3-bis(indol-3-yl)-y-butyrolactam (1474) in 87% yield. Oxidative cyclization of the ds-lactam 1474 with DDQ in the presence of catalytic amounts of p-TsOH led to staurosporinone (293) (791) (Scheme 5.249). 

Lactams are named in several ways. They are named as alkanolactams by the IUPAC substitutive system, such as 3-propanolactam, 4-butanolactam, 5-pentanolactam, and 6-hexano-lactam, respectively, for the 4-, 5-, 6-, and 7-membered rings, respectively. An alternate IUPAC method, the specialist heterocyclic nomenclature system, names these lactams as 2-azetidinone, 2-pyrrolidinone, 2-piperidinone, and hexahydro-2f/-azepi n-2-one, respectively. These lactams are also known by the trivial names fl-propiolactam, a-pyrrolidone (y-butyrolactam), a-piperidone (8-valerolactam), and e-caprolactam, respectively. 

The first oxidation by a Ru complex of an amide was carried out by Berkowitz and Rylander in 1958, using stoich. RuOyCCl to convert y-butyrolactam to suc-cinimide [52]. 

Thus, the 1,4-addition of the lactams 72 to nitroolefins provided access to the Michael adducts 73 with good stereoselectivities, which could be improved by recrystallization or chromatography. After reduction and protection of the amino group the y-butyrolactams 74 were converted to the corresponding a-substituted lactams 75 in good overall yields (37-65%) and excellent diastereo- and enantio-... 

There are also a number of species for which a tetrahedral intermediate-like structure has been claimed but which require substantiation before the claims can be fully accepted. Thus, on the basis of infrared spectroscopic evidence it was claimed that y-butyrolactam, on treatment with concentrated (23%) potassium hydroxide solution, is converted into the ionized tetrahedral intermediate [52] characterized by a band at 1555 cm-1 (Vinnik and Moiseyev, 1963). However, this interpretation has been criticized (Robinson,... 

When /V-(2-hydroxyacetyl)-2-pyrrolidone (83) (Scheme 23) was dissolved in water at pH > 8, irreversible cleavage of the exocyclic and endocyclic amide C-N bond occurs. The former led to y-butyrolactam (87) and glycollic acid (88). The latter, a... 

For the corresponding cyclization of acetylenic amides 418, Nagasaka etal.347,347a used a mixture of silver(i) triflate and lithium hexamethyldisilazide as the precatalyst. The process is probably initiated by the coordination of AgN(SiMe3)2 (generated in situ from AgOTf and LHMDS) to the triple bond, followed by nucleophilic attack of the lithium amide at the activated alkyne which affords (ZVy-alkylidene-y-butyrolactams 419 in high yields (Scheme 122). 

A highly enantioselective and general rhodium(I)-catalysed intramolecular Alder-ene reaction has been developed. a-Methylene-y-butyrolactones, a-methyl-ene-y-butyrolactams, polyfunctional cyclopentanes, cyclopentanones, and functionalized tetrahydrofurans were formed in high yields and excellent enantiomeric... 

Recently, catalytic hetero-[2 + 2 + 1]-cycloaddition of a carbon—carbon multiple bond, a carbon—heteroatom bond, and carbon monoxide, the so-called hetero-Pauson—Khand reaction, has been used frequently for the synthesis of functionalized y-butyro-lactones and y-butyrolactams 381 (Scheme 120). 

Imhof et al. and Chatani et al. independently reported that the ruthenium-catalyzed reaction of the a,/3-unsaturated imines 483 with alkenes and carbon monoxide gave the / ,y-unsaturated y-butyrolactams... 

---