Pyrrolidinones, unsaturated

Selective 1,4-reduction of unsaturated aldehydes and ketones by 6 occurs smoothly in THF between —25 °C and room temperature within a few hours (Eq. 5.7). Particularly noteworthy is the realization that phosphines are noticeably absent from the reaction medium. The analogous combination of CuCl/BusSnH in N-methyl-2-pyrrolidinone (NMP) or DMF does not behave identically [22], failing to react with the hindered substrate isophorone, whereas a 72% yield of the corresponding reduced ketone is formed with reagents XCu(H)Li/Bu3SnH. Nonetheless, a form of CuH is being generated in this more polar medium, effectively utilized by Tanaka to arrive at 3-norcephalosporin 8 upon reaction with allenic ester 7 (Scheme 5.3). 

Scheme 6.68 Typical adducts obtained from the 12-catalyzed asymmetric Michael reaction between malononitrile and a.P-unsaturated N-acyl pyrrolidinones (cyclic imides) the values in parentheses refer to reactions at lower concentration (0.1 M).

Scheme 6.70 Mechanistic proposal for the 12-catalyzed asymmetric Michael addition of malononitrile to (J-aryl and alkyl substituted N-acyl pyrrolidinones (cyclic imide) (A) and to a,P-unsaturated N-aryl substituted 2-methoxybenzamides such as N-cinnamoyl-2-methoxybenzamide (acyclic imide) (B).

Flydroformylation A catalyst solution consisting of dicarbonylacetylacetonato rhodium (I) (0.063 g) and dicyclohexyl-(3-sulfonoylphenyl)phosphine mono sodium salt (1.10 g) in n-methyl pyrrolidinone (NMP) (16.0 g) was placed in a 100 mL stainless steel autoclave at 75 C under 200 psig synthesis gas. After 15 minutes soy methyl esters (34.05 g) were added and the synthesis gas pressure raised and maintained at 400 psig for 3 hrs resulting in the desired conversion of unsaturation. 

Pyrrolidinones with a chiral C-5 atom have been prepared in a very simple, one-pot synthesis, by treatment of TV-alkoxycarbamoyl y-amino a,/J-unsaturated carboxylates with Mg in methanol (equation 168)602. The products are formed in 87-95% yield, with high optical purity (96-99% ee). Since this y-lactam is very important, as an intermediate and target in the synthesis of natural products, this simple reaction is a very useful addition to the synthetic chemist s arsenal. Most other preparations of this target usually lead to racemic mixtures603-606. 

IBX-oxidations of unsaturated TV-aryl amides and urethanes proceed more efficiently and provide access to a substantial variety of pyrrolidinones and oxazolidinones, examples of which are shown in Scheme 92 (00AGE625, 01AGE202, 02JA2233). 

In the course of a study of structure-based design and synthesis of a potent matrix metallo-proteinase-13 inhibitor based on a pyrrolidinone scaffold, the Suzuki coupling reaction of a,/ -unsaturated /-lactam iodide (40) with 4-methoxyphenylboronic acid was carried out to give the corresponding coupling product in 77 % yield (Eq. (76)) [119]. 

The nucleophilic cleavage of aryl alkyl ethers gives the corresponding phenol with only 1 equiv. of thiophenol in the presence of N-methyl-2-pyrrolidinone (NMP) in a catalytic amount of potassium carbonate. The aromatic nitro and chloro substituents which are displaced with stoichiometric thiolates are preserved by this method. Moreover, a(B-unsaturated carbonyl compounds do not undergo Michael addition of thiolate under these conditions. 

Procedures have been developed for the phenylselenenylation and oxidative elimination of P-formyl ketones and aldehydes to form the corresponding a,p-unsaturated aldehydes (Schemes 29 and 30). Other P-dicarbonyl compounds have also been oxidized to the corresponding a,P-unsaturated compounds by phenylselenenylation and oxidative elimination including 3-(l-oxotrienyl)pyrrolidinones,... 

Many chiral phosphorus ligands with Ru complexes have achieved excellent enantioselectivity in the hydrogenation of a,P-unsaturated esters, amides, lactones, and ketones. The Ru-BINAP system is efficient for hydrogenation of 2-methylene-y-butyrolactone 64 and 2-methylene-cyclopentanone 66.56,57 With a dicationic (5)-di- -Bu-MeOBIPHEP-Ru complex under high hydrogen pressure, 3-ethoxy pyrrolidinone 68 is hydrogenated to give (/ )-4-ethoxy- -lactam 69 in 98% ee.58... 

In a related manner but at ambient presure, unsaturated esters have been derived by, for example in 85% yield, the reaction of N-vinyl-2-pyrrolidinone with... 

Dienes in which the double bonds are separated by 4, 5, or 6 bonds, and linked through amine or amide functions, readily undergo RCM in the presence of various initiators to yield substituted unsaturated cyclic amines or amides (pyrrolidinones, piperidinones, piperidines) see Table 8.4. 

Besides the above materials, imsaturated ultra low molecular weight (ULMW) poly (L-lactide) (PEA) (ULMW PLA), can also be used as an injectable in situ crosslinkable macromer for tissue engineering. Jabbari and He mixed ULMW PLA with fumaryl chloride to make unsaturated in situ crosslinkable poly (lactide fumarate) (PLAF) macromer. When this PLAF macromer was injected and crosslinked widi l-vinyl-2-pyrrolidinone (NVP) in the presence of NaCl crystals as porogen, porous scaffold was formed in situ (Jabbari and He, 2008). These porous scaffolds showed osteoconductive behavior and led to new bone formation when implanted in nude mice. 

Based on previously performed studies on p-turn peptides for asymmetric acylation reactions, the group of Miller expanded the application of such catalysts to the asymmetric conjugate addition of azides to a,p-unsaturated carbonyl compounds (Scheme 13.9a). A screening of several p-turn containing peptides disclosed catalyst 10 as the appropriate catalyst for the preparation of a series of p-azido-pyrrolidinone-derived imides in good yields and with enantioselectivities up to 85%. The obtained products can be further processed towards N-Boc-protected p-amino acids. Subsequent... 

Additionally, as pointed out earlier (Chapter 7, Section D7) with regard to vinyl halides, the Stille vide supra) reaction affords substitution of the leaving group by a carbon nucleophile at the site of unsaturation. Thus, as shown in the Equation 8.26, when the enol trifluorosulfonate (trillate, -OSO2CF3, -OTf) of 4-tert-butylcy-clohexanone (Chapter 9) is treated with tri-n-butylphenylstannane in the presence of a palladium catalyst (tris(dibenzylideneacetone)palladium, Pd2(dba)3) in a polar aprotic solvent (l-methyl-2-pyrrolidinone, A-methylpyrrolidinone [NMP]), substitution is readily affected. 

Likewise, 2-silyldihydropyrans and furans can be prepared by heating the corresponding bromo- or cbloroacylsilanes in Al-methyl-2-pyrrolidinone (NMP) in tbe presence of potassium iodide as shown in eqs 25 and 26, respectively. Treatment of unsaturated acylsilanes with either iodine or phenylselenenyl bromide generates the cyclized iodides or selenides (eqs 27 and 28). ... 

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