Bis-y-butyrolactones

Bis--Y-butyrolactones can also be obtained in this way. An example is the synthesis of canadensolide (1). 

It is interesting that unsaturated polyesters can actually be prepared by anionic alternating copolymerization of an epoxide and bicyclic bis(y-butyrolactone) bearing an isopropenyl group [34]. The reaction was illustrated as follows ... 

As part of a syndietic q>proach to squalestatin 1,1,6-anhydrogalactose has been converted to intermediate isomeric butenolides and thence to the spirolactone 65, an intermediate towards the natural product (For other synthetic approaches see Section 4). The l,7-dioxaspiro[4.4]nonane bis-y-butyrolactone 67 has been prepared as a rigid diacylglycetol analogue starting from L-xylose and... 

Allerheiligen, S. and Bruckner, R. (1997) Total synthesis of the Tolypothrix pentaether via a bis(y-butyrolactone)- — 1,3,7,9-tetraol route. Liebigs Ann. Chem., 1667-1676. 

Several procedures for making glutaric acid have been described in Organic Syntheses starting with trimethylene cyanide (28), methylene bis (malonic acid) (29), y-butyrolactone (30), and dihydropyran (31). Oxidation of cyclopentane with air at 140° and 2.7 MPa (400 psi) gives cyclopentanone and cyclopentanol, which when oxidized further with nitric acid at 65—75° gives mixtures of glutaric acid and succinic acid (32). 

The chiral acrylate 164 was used in a 1,3-dipolar cycloaddition with a nitrile imine. Bis(trityl)nitrile imine was found to undergo a diastereoselective 1,3-dipolar cycloaddition with (f )-a-(acyloxy)-p,p-dimethyl-y-butyrolactone 164 to give the 2-pyrazoline product with a de of 50% (Scheme 12.51) (275). 

The method has been extended to other polyfunctionnal systems, such as O-ethyl S-(tetrahydro-2-oxo-3-furanyl)dithiocarbonate. Treatment of y-butyrolactone with bis [methoxy(thiocarbonyl)]disulfide in the presence of 2.2 equivalents of lithium diisopropy-lamide at —78 °C in THF provides the lithium enolate which reacts with MgCla to furnish the magnesium enolate (equation 17). 

Only three constituents have been reported from Broussonetia zeylanica, all by a group at the University of Peradeniya in Sri Lanka [89-91]. A major alkaloid, 8-hydroxyquinoline-4-carbaldehyde (55), was identified as an antimicrobial agent active against Staphyllococus aureus and Candida albicans (the levels of activity were not specified) [89] and then two minor compounds, 3,4 -dihydroxy-2,3 -bipyridine (56) and 3,4-bis(8-hydroxyquinolin-4-yl)-y-butyrolactone (broussonetine, 57), were reported, Fig. (10) [90,91]. However, the structure of 3,4 -dihydroxy-2,3 -bipyridine (56) was revised to 8-hydroxyquinoline-4-carbaldehyde oxime (58) by synthesis [92,93]. Also, it was noted that an artefactual origin of this oxime (58) could not be ruled out due to the presence of the corresponding aldehyde (55) [93]. 

A new Y solvolysis scale has been developed for benzylic species with extensive charge delocalization, based upon the solvolyses of some benzhydryl bromides and /-butyl(2-naphthyl)methyl bromides.39 Chlorides have negative salt effects on the ionization of benzhydryl bromide in y-butyrolactone.40 The X-ray structure of the dimerization product of l,8-bis(dimethylammonio)-4-naphthyl(phenyl)methyl carbocation has been determined it appears to be formed via a 4n + 271-cycloaddition mechanism.41... 

Stable /V-phosphino- and /V-phosphonio-nitrilimines undergo 3 + 2-cycloaddition with electron-poor and electron-rich dipolarophiles, respectively, to produce substituted pyrazolines.101 The first diastereoselective 3 + 2-cycloaddition between bis(trityl)ni-trilimine and an acrylate, (R)-a-(acryloxy)-/f, jS-dimethyl-y-butyrolactone, has been reported.102 The 1,3-dipolar cycloaddition of A, A -diarylbisnitrile imides with cinnamonitriles produces exclusively 5, 5 -dicyano-4,4, 5, 5 -tetrahydro[3, 3 -di-l//-pyrazoles] which yield the corresponding 3,3 -di-l//-pyrazoles on thermal aromatization.103... 

Intramolecular cyclopropanation of allyl diazoacetates gives rise to interesting cyclopropane-fused y-butyrolactones. A chiral ruthenium bis(oxa-zolinyl)pyridine complex 85 was employed for the catalytic cyclization of trans-cinnamyl diazoacetate 83 at room temperature to obtain an optically active lactone 84 in 93% yield with 86% ee (Eq. 34, Fig. 2) [85]. Chiral porphyrin and salen complexes of ruthenium 86 [86] and 87 [87] also catalyzed the asymmetric intramolecular cyclopropanation of 83 to afford 84 in similar yields and enantiomeric excess. 

A wide variety of substituted y-butyrolactones can be prepared directly from olefins and aliphatic carboxylic acids by treatment with manganic acetate. This procedure is illustrated in the preparation of 7-( -OCTYL)-y-BUTYROLACTONE. Methods for the synthesis of chiral molecules are presently the target of intensive investigation. One such general method developed recently is the employment of certain chiral solvents as auxiliary agents in asymmetric synthesis. The preparation of (S.SM+H, 4-BIS(DIMETHYLAMINO)-2,3-DIMETHOXY-BUTANE FROM TARTARIC ACID DIETHYL ESTER provides a detailed procedure for the production of this useful chiral media an example of its utility in the synthesis of (+)-(/ )-l-PHENYL-l-PEN-TANOL from benzaldehyde and butyllithium is provided. 

As noted in the discussion of ( )-selective alkene formation, Kishi has found that a-substituted aldehydes reacted with trimethylphosphonopropionate and KOBu to produce the (Z)-alkene selectively. A strongly dissociating base is critical to this approach. In addition to the examples already presented in the discussion of ( )-alkene formation, the (Z)-selective reaction has recently been applied to the synthesis of macrolide antibiotics. In this example, a trisubstituted alkene was formed and closed to the lactone (148 equation 33). In an application to diterpenoids. Piers encountered an example of how substrate-specific the alkene formation can be. With a-dimethoxyphosphonyl-y-butyrolactone (150), the reactions with simple aldehydes proceeded with very high selectivity [(Z) ( ) = 99 1]. On application of the reaction to the more complex aldehyde (149) the (Z) ( ) stereoselectivity dropped to 3 1 in 58% yield (equation 34). No selectivity was observed on reaction with benzaldehyde. Although for hindered substrates, strongly basic conditions with a dimethyl phosphonate can be a simple and effective method for the synthesis of (Z)-isomers, the reaction is not general. In 1983, Still and coworkers introduced methodology that used bis(trifluoroethyl)phosphonoesters (153) to provide a facile approach to (Z)-aIkenes (154) when reacted with aldehydes (equation 35). " ... 

There have again been a number of reports relating to the use of O2 in non-traditional environments. Thus the O2 oxidation of electron-rich substrates such as quinol, 1-naphthol and anthracene with bentonite-bound methylene blue and hydrotalcite-bound rose Bengal has been described. These clay-bound sensitizers have been recovered and reused up to three times with only a small loss in efficiency, and, it is claimed, are more stable with respect to bleaching. The fullerene-coated beads already described (Scheme 7) have been used to promote the conversion of 1-naphthol to 1,4-naphthoquinone. The conventional methylene blue sensitized oxidation of 3-bromo-2,5-bis-(thio)furans affords thiomaleates (Scheme 16) which have synthetic potential as dienophiles and Michael acceptors. The 3-bromo-2-thiofuran (105), in a similar fashion, gives a 4-oxobutanethioate whereas the 2,3-bis-(thio)furan (106) gives a y-butyrolactone. 

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