A,p-Unsaturated butyrolactones

Asymmetric aziridination of a,P-unsaturated esters by use of N-nitrenes was studied in great detail by Atkinson and co-workers [34, 35]. Here, lead tetraacetate-mediated oxidative addition of N-aminoquinazolone 30 (Scheme 3.10) to a-methy-lene-y-butyrolactone 32 was reported to proceed with complete asymmetric indue-... 

The intermediate a-sulfenyl carbonyl compounds may be alkylated prior to oxidative elimination. Phe-nylsulfenylation of the cw-fused butyrolactone (61), followed by methylation and oxidative elimination, gave the a-methylenebutyroiactone (62) because endocyclic elimination is stericaliy inhibited (Scheme 6). For the tran -fused butyrolactone (63), the alkylation was carried out first to ensure exocyclic elimination (Scheme 1). The intermediate a-sulfinylcarbonyl compounds may also be modified before elimination, the alkylation of keto sulfoxides (64) providing a useful synthesis of a,p-unsaturated -y-keto esters (65 Scheme In some cases the use of an excess of strong base provides a dimetaliated... 

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

NaBHj/NiC or Raney nickel, the menthyloxy group is removed with NaBH /KOH to give 3,4-disubstituted butyrolactones with a high diastereo- and enantioselectivity (Figure 7.69). Corey and Houpis [1458] have described asymmetric Michael reactions of ketone enolates with a 2-thiophenyl crotonate of 8-phenmenthol. Chirality has also been introduced on the amino group of 2-ami-nomethyiacrylates to perform the asymmetric addition of the anion of the tert-Bu ester of cyclopentanecarboxylate [1459], More important developments have been reported with chiral a,p-unsaturated sulfoxides and nitro compounds as Michael acceptors (see below). 

BINAPO (the bis-oxide of BINAP) can complex samarium and gives some stereocontrol in the formation of y-butyrolactones by reaction of ketones with a,p-unsaturated esters and Sml2 in THR Enantiomeric excesses (ee s) of up to 90% were obtained [106]. 

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... 

It is interesting that upon illumination, the complex RhCl(CO)(PMc3)2 catalyzes carbonylation of liquified propane at room temperature to yield butanal with high regioselectivity [48], The reaction of some C-H compounds with carbon monoxide and ethylene or other olefins in the presence of metal carbonyls results in carbonylation at a C-H bond [49] (Scheme IV-25). The carbonyl Ru3(CO)i2 catalyzes the cyclocarbonylation of yne-aldehydes to bicyclic a,p-unsaturated y-butyrolactones [49d],... 

The pivotal step associated with our approach to compounds 31-34 was an organocatalysed, enantioselective and intramolecular Michael addition reaction of the nucleophilic C-2 carbon of a pyrrole to an iV-tethered a,p-unsaturated aldehyde residue and thereby estabhshing the required CD-ring system. Full details of the reaction sequence are shown in Scheme 4 and this involves initial reaction of the potassium salt, 35, of pyrrole with butyrolactone (36) to give, after acidic workup, compound 37 (60-90%). Conversion of this last species into the corresponding Weinreb amide 38 (87%) followed by its reaction with ethylmagnesium bromide then afforded the ethyl ketone 39 (95%) that was subjected to standard Homer-Wadsworth-Emmons (HWE) conditions and thereby generating the... 

The first report concerning the additive Pummerer reaction of a,P-unsaturated sulfoxides with dichloroketene appeared in 1981 [220], and work in this area has recently been reviewed [221]. Simple a,P-unsaturated sulfoxides such as (282) react with dichloroketene (generated from the addition of trichloroacetyl chloride to zinc) to produce diastereoisomerically pure c -y-butyrolactones such as (283) (Scheme 5.93) [220]. 

P,P-Disubstituted alkylidene derivatives of oxindole, azlactone, and y-butyrolactone are used as precursors of vinylogous enolates, which are highly stabilized owing to the heteroaromatic nature of the enolate components. Although these a,p-unsaturated carbonyl systems can act as electrophilic Michael acceptors, the presence of two p-substituents seems to suppress nucleophilic attack on the P-carbon. 

This new method for the construction of a-hydroxy-y-lactones is quite general for a variety of alcohols and a,P-unsaturated esters (Figure 6.9). The preparation of a-hydroxy-y-spirolactones from cyclic alcohols is especially notable, because these spirolactones have been very difficult to synthesize until now. The reaction can be explained by Scheme 6.18 (i) in situ generation of an a-hydroxy carbon radical from an alcohol assisted by NHPI/Co(II)/02, (ii) the addition of the radical to methyl acrylate, (iii) trapping of the adduct radical by O2, and (iv) intramolecular cydization to give a-hydroxy-y-butyrolactone. Considering the low-cost material, reaction efficiency, and reaction simplicity, this method provides an innovative approach to a-hydroxy-y-lactones which has considerable industrial potential. 

A variant of these reactions was optimized based on the Hosomi-Miyaura borylation of a,P-unsaturated carbonyl compounds with nucleophilic boryl copper, providing 2-alkoxycarbonyl (as well as 2-acyl- and 2-cyano) allylboronates such as 40 in high stereoselectivity (Equation 22) [60]. The resulting 2-alkoxycarbonyl reagents react with aldehydes to provide a-methylene-y-butyrolactones. 

Procter and coworkers" have described a Sm(II)-mediated (106), asymmetric capture and release approach (Scheme 7.22) to y-butyrolactones (107) that involves intermolecular radical additions to a,[3-unsaturated esters (105) attached to resin through an ephedrine chiral linker (108). Resin capture-release is a hybrid technique that combines elements of traditional solid-phase synthesis and the use of supported reagents. Fukuzawa s Sm(II)-mediated, asymmetric method to y-butyrolactones was chosen to demonstrate the feasibility of such a process. y-Butyrolactones (107) were obtained by capture of a reactive intermediate from solution through an asymmetric transformation starting from a,p-unsaturated esters (105) immobilized on an ephedrine chiral resin. Lactone products were obtained in moderate yields with selectivities up to 96% ee. Nevertheless, the ephedrine resin can be efficiently reused for many cycles although in some cases lower yields were obtained on reuse of the chiral resin. 

Butyrolactones.—Cathodic crossed-coupling of a,p-unsaturated esters with... 

Burstein, C., Glorius, F. (2004). Organocatalyzed conjugate umpolung of a,p-unsaturated aldehydes for the synthesis of y-butyrolactones. Angewandte Chemie International Edition, 43,6205-6208. 

Rojo J, Garcia M, Carretero JC. Stereoselective synthesis of substituted y-butyrolactones from y-hydroxy-a,p-unsaturated phenyl sulfones. Tetrahedron 1993 49 (43) 9787-9800. 

Durchschein, K., Wallner, S., Macheroux, P., Zangger, K., Fabian, W.M.F., and Faber, K. (2012) Unusual C=C bond isomerization of an a, 3-unsaturated y-butyrolactone catalysed by flavoproteins from the old yellow enzyme family. ChemBioChem, 13, 2346-2351. 

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