Y-Butyrolac tones

From ethyl 2-bromomethyl-8-oxo-2-octenoate, a d.v-fused bicyclic a-methylene-y-butyrolac-tone 7 is obtained in one synthetic step16. 

As mentioned above, several syntheses of optically active y8-benzyl-y-bu-tyrolactones have been reported in the literature [1, 2]. A comprehensive overview of the methods available for the synthesis of / -benzyl-y-butyrolac-tones is displayed in Scheme 6. Asymmetry was introduced involving either... 

Zhang has applied the cyclization of esters to the formation of a-methylene-y-butyrolac-tones, providing a novel and enantioselective entry to these substructures. The importance of this type of unsaturated lactone is evident by its ubiquitous presence in nearly one-third of all naturally occurring secondary metabolites. The Alder-ene reaction has been applied to a formal total synthesis of (+)-pilocarpine [26], a leading therapeutic reagent for the treatment of narrow and wide glaucoma. Zhang intersected Biichi s synthetic intermediate (i )-10a [27] in only two steps with 99% enantiomeric excess in 91% overall yield (Eq. 13). In comparison, Biichi synthesized (il)-lOa in five steps with 92% enantiomeric excess and 20% overall yield. 

Recently, the influence of y-butyrolac-tone cyclohexanone [357] and propanal... 

Pohmakotr, M. Sampaongoen, L. Issaree, A. Tuchinda, P. Reutrakul, V. Vicinal dianions of diethyl a-aroylsucdnates a general synthetic route to a-aroyl- and a-arylidene-y-butyrolac-tones. Tetrahedron Lett. 2003, 44, 6717—6720. 

Hydroxy-y-butyrolactone 5-Ethoxy-5-hydroxy-y-butyrolac tone + +... 

Enantiomer separation of various compounds such as barbituric acids, benzoin, MTH-proline, glutethimide, a-methyl-oc-phenyl-succinimide, y-phenyl-y-butyrolac-tone, methyl-mandelate, l-(2-naphthyl)ethanol, mecoprop methyl, diclofop methyl and fenoxaprop methyl by pressure supported CEC on a permethyl-P-cyclodextrin modified stationary phase was described by Wistuba and Schurig [42-44]. Three different separation beds were used (i) permethyl-P-cyclodextrin was covalently attached via a thioether to silica (Chira-Dex-silica) [42], permethyl-P-cyclodextrin was linked to a dimethylpolysiloxane and thermally immobilized (ii) on silica (Chirasil-Dex-silica) [43] or (iii) on a silica monolith (Chirasil-Dex-monolith) [44], respectively. 

In the newest method of synthesis, which allows the large-scale production of SeMet, L-Met is first converted to the methyl-methionium derivative, which is hydrolyzed to homoserine and converted to a-amino-y-butyrolac-tone. The latter is reacted with HBr to 2-amino-4-bromobutanoic acid, from which L-SeMet is obtained on reaction with LiSeCH3 (Koch and Burchardt, 1993 Krief et al., 1994). 

PC = propylene carbonate EC = ethylene carbonate DMC = dimethyl carbonate DEC = dimethyl carbonate MF = methyl formate y-BL = y-butyrolac-tone THF = tetrahydrofuran 2Me-THF = 2-methyltetrahydrofuran DME = dimethoxyethane 1,3-DN = 1,3-dioxolane EMC = ethyl methyl carbonate ... 

Figure 7. Vapor phase FTIR spectra taken from HRGC-FTIR study of fermentation byproducts (12). Top 2-methyl-l-propanol (left) 2-phenylethanol (right). Bottom ethyl lactate (left) Y-butyrolac-tone (right).

Alternate Name (R)- and (5)-y-hydroxymethyl-y-butyrolac-tones 5-oxotetrahydrofuran-2-methanol 5-hydroxymethylpenta nolide. 

While the reaction of 2-aminobenzylamine with 3-hydroxy-y-butyrolac-tone (265) at 200 C under a nitrogen atmosphere gave 3-hydroxytetrahy-dropyrrolo[2,l-6]quinazoline (184) directly, the reaction with y-butyrolac-tone yielded 2-(3-hydroxypropyl)-3,4-dihydroquinazoline (122). Compound 122 was cyclized with phosphoryl chloride to a 1 2 mixture of the linear isomer 124 and the angular isomer 123 (see Section IV,A, 1). 

Additions are found in the aminogermanation ring-opening of y-butyrolac-tone or the anhydride of succinic maleic", or o-phthalic acid ... 

Carboxyl groups were also introduced at the a-end of poly(methacrylate)s134 235 320 and polystyrene330-331 by using unprotected and protected initiators. 2-Bro-moisobutyric acid (FI-7) was employed for MMA coupled with CuBr/L-9 (R = n-Pen)235 and with Ni-2134 to give narrow MWDs (Mw/Mn = 1.1 —1.3) but Mn values higher than the calculated values. This unprotected initiator, on the other hand, has poor efficiency = 0.10) for styrene, probably because of the intramolecular cyclization into a y-butyrolac-tone after addition of one styrene unit.330 Protection... 

The same cluster catalyzes in the presence of HI the reaction of isoprene with CO and H20 to give pyroterebic acid and y,y-dimethyl-y-butyrolac-tone [Rh4(CO)12, HI, H20, THF, 50-bar CO, 120°C, yield 88%, CT44, acid/lactone 0.05] the stoichiometry of the overall reaction is not clear... 

Treatment of diethyltrichloromethylphosphonate with butyllithium followed by an aldehyde or cycloalkenone leads to a-chlorovinylphosphonates (89). Pyranosic 3,4-enuloses exhibit anomalous behaviour when treated with the enolate of dimethyl(methoxycarbonyl)-methylphosphonate, leading to phos-phorylated products. The synthesis of a-(alkyl)methylene-Y-iodo-Y-butyrolac-tones has been accomplished in high yields, but with poor selectivity, from the reaction of a-phosphono-y-iodo-Y-butyrolactones and aldehydes. ... 

Addition of sulfur nucleophiles such as phenylthiolate to diethyl l-(ethoxycarbonyl)vinylphos-phonate has been used in the synthesis of P-acetoxy- and p-hydroxy-a-methylene-y-butyrolac-tones Similarly, addition of isopropylthiolate to diethyl l-(ethoxycarbonyl)vinylphosphonate represents a key step in the synthesis of a-methylidenebutyrolactones such as confertin (Scheme arteannuin B, - - rhopaloic acid and hippospongic acid A Addition... 

Optically active products formed by such reductions may serve as useful intermediates in organic syntheses. A concept for a new total synthesis of natural a-tocopherol has been proposed27 where the optically active C5 units, (5)-3-methyl-y-butyrolactone or (5)-2-methyl-y-butyrolac-tone, were used to build up the side chain. Both compounds are broadly applicable optically active building blocks for the syntheses of chiral compounds and have been prepared by stereospecific reduction of suitable unsaturated precursors. 

Haddad, M. Molines, H. Wakselman, C. Preparation of P-Trifluoromethyl-Y-butyrolac-tones via Claisen Rearrangement. Synthesis 1994, 167-169. 

In this reaction, the 7r-bond of the ketone or aldehyde, the jr-bond of the alkene, and the carbon atom of CO are integrated into compounds with a five-membered ring, such as y-butyrolac tones. ... 

Maleic anhydride is also used, in competition with acetylene, as a starting material for the production of 1,4-butanediol. Partial hydrogenation of maleic anhydride in the liquid phase (250 °C, 140 bar) on a nickel catalyst yields y-butyrolac-tone, a starting material for Vitamin Bi. 

SETCHELL, K.D.R., A.M. LAWSON, E. CONWAY, N.F. TAYLOR, D.N. KIRK, G. COOLEY, R.D. FARRANT, S. WYNN, M. AXELSON. 1981. The definite identification of the lignans trans-2,3-bis(3-hydroxybenzyl)-Y-butyrolac-tone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol in human and animal urine. Biochem. J. 197 447-458. AXELSON, M., K.D.R. SETCHELL. 1981. The excretion of lignans in rats - evidence for an intestinal bacterial source for this new group of compounds. 

Zhou, J. Lu, G. Wu, S. (1992) A new approach for the synthesis of a-methylene-y-butyrolac-tones from a-bromomethylacrylic acid (or esters), Synth. Commun., 22,481-7. 

A different behavior is correlated with the use of y-butyrolac-tone, which does not homopolymerize and acts as a classical activator leading to a slower polymerization, lower polymer yield, and lower degrees of polymerization, mainly due to the presence of side reactions and the absence of transacylation reactions. ... 

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