Y-butyrolactone derivative

When (R,R)-Me-Duphos, (R,R,R,R)-BICPO [9] or BINAP [10] is used, the rhodium-catalyzed asymmetric cycloisomerization of 3 affords 4 with up to >99.5% enantiomeric excess (Scheme 7 2). This methodology was applied to the synthesis of functionalized a-methylene-y-butyrolactone derivatives 6 such as (-i-)-pilocarpine 7 (Scheme 7.3) [11]. 

Ethyl a-(bromomethyl)acrylate has proved to be an excellent reagent for conversion of aldehydes and ketones, both acyclic and cyclic, into the corresponding a-methylene-y-butyrolactone derivatives4"9 in a Re-formatsky type reaction. The yield was excellent in the case of several spiro a-methylene-y-butyrolactones.10 Synthetic a-methylene-y-butyrolactone derivatives have been shown to possess antitumor activity.5 6,7 1112 Ethyl a-(bromomethyl)acrylate has also proven of value in the synthesis of alkylated products of enol ethers of cyclohexane-1,3-dione.13... 

Franot, C., Roberts, D.W., Basketter, D.A., Benezra, C. and Lepoittevin, J.-P. (1994) Structure-activity relationships for contact allergenic potential of Y,Y-dimethyl-Y-butyrolactone derivatives. 2. Quantitative structure-skin sensitization relationships for cxrSubstituted-a-methyl-Y,Y-dimethyl-y-butyrolactones. Chem. Res. Toxicol.,... 

Further biotransformations of A VPA involve both the liver microsomal cytochrome P-450 enzymes and the fatty acid 3-oxidation pathway (Fig. 32.28). The mixed-function oxidase system metabolizes the unsaturated metabolite to a y-butyrolactone derivative through a chemically reactive entity that is a suicide-substrate inhibitor of cytochrome P-450. The alkylation of the prosthetic haem by means of the radical occurs prior to the formation of the epoxide. Thus the epoxide is not involved in the cytochrome P-450 inhibition. 

Walkup and co-workers developed new methodologies for the efficient synthesis of tetrahydrofurans 111 and y-butyrolactone derivatives 112, respectively, using the Pd(0)-catalyzed cyclization of organyl halides with 4,5-dienols and 4,5-dienoic acids, respectively (Scheme... 

Koga, Y, Sodoeka, M. and Shibasaki, M. (1994) Palladium-catalyzed asymmetric arylation of 4,7-dihydro-l,3-dioxepin. Catalytic asymmetric synthesis of y-butyrolactone derivatives. Tetrahedron Lett., 35, 1227-30. 

P-Amino acid derivatives of the (R)-series have been obtained from the P-tosylamino-y-butyrolactone derived from 1-aspartic acid, as shown in Scheme 7.56 (Jefford et al. 1996). 

The diastereoselectivity in the Pd(II)-LiX-CuX2-catalyzed cyclization of 2 -alkenyl 2-alkynoates is similar to that in the Pd(II)-LiX-catalyzed cyclization of 4 -het-eroatom-2 -alkenyl 2-alkynoates. The similar diastereoselectivity was observed in the synthesis of a-alkylidene-y-butyrolactams. The diastereoselectivity is further supported by the cascade cyclization reaction. A monocyclic product was obtained in the reaction of l, 5 -hexadien-3 -yl propynoate. The failure of the second cyclization might be due to the trans-configuration of the /S.y-disubstituents in the product. The reaction of r,5 -hexadien-3 -yl 3-substituted 2-aIkynoates under the same conditions yielded the cw-fused bicyclic a-(Z)-chloroalkylidene- y-butyrolactone derivatives implying the cw-diastereochemistry of the /3,y-disubstituents in the first cyclization (Scheme 16). 

Activated zinc has been found to promote the reaction of dimethyl maleate with carbonyl compounds to give y-butyrolactone derivatives in yields between... 

Butanediol. 1,4-Butanediol [110-63-4] made from formaldehyde and acetylene, is a significant market for formaldehyde representing 11% of its demand (115). It is used to produce tetrahydrofuran (THF), which is used for polyurethane elastomers y-butyrolactone, which is used to make various pyrroHdinone derivatives poly(butylene terephthalate) (PBT), which is an engineering plastic and polyurethanes. Formaldehyde growth in the acetylenic chemicals market is threatened by alternative processes to produce 1,4-butanediol not requiring formaldehyde as a raw material (140) (see Acetylene-derived chemicals). 

Much more important is the hydrogenation product of butynediol, 1,4-butanediol [110-63-4]. The intermediate 2-butene-l,4-diol is also commercially available but has found few uses. 1,4-Butanediol, however, is used widely in polyurethanes and is of increasing interest for the preparation of thermoplastic polyesters, especially the terephthalate. Butanediol is also used as the starting material for a further series of chemicals including tetrahydrofuran, y-butyrolactone, 2-pyrrohdinone, A/-methylpyrrohdinone, and A/-vinylpyrrohdinone (see Acetylene-DERIVED chemicals). The 1,4-butanediol market essentially represents the only growing demand for acetylene as a feedstock. This demand is reported (34) as growing from 54,000 metric tons of acetylene in 1989 to a projected level of 88,000 metric tons in 1994. 

Apart from lactic and hydroxyacetic acids, other a- and P-hydroxy acids have been small-volume specialty products produced in a variety of methods for specialized uses. y-Butyrolactone [96 8-0] which is the monomeric inner ester of y-hydroxybutyric acid [591-81-17, is a large-volume chemical derived from 1,4-butanediol (see Acetylene-derived chemicals). 

Reduction. Heterogeneous catalytic reduction processes provide effective routes for the production of maleic anhydride derivatives such as succinic anhydride [108-30-5] (26), succinates, y-butyrolactone [96-48-0] (27), tetrahydrofuran [109-99-9] (29), and 1,4-butanediol [110-63-4] (28). The technology for production of 1,4-butanediol from maleic anhydride has been reviewed (92,93). 

The potential for use of chiral natural materials such as cellulose for separation of enantiomers has long been recognized, but development of efficient materials occurred relatively recently. Several acylated derivatives of cellulose are effective chiral stationary phases. Benzoate esters and aryl carbamates are particularly useful. These materials are commercially available on a silica support and imder the trademark Chiralcel. Figure 2.4 shows the resolution of y-phenyl-y-butyrolactone with the use of acetylated cellulose as the adsorbent material. 

Further examples of the utility of the allylic sulfoxide-sulfenate interconversion in the construction of various biologically active natural products include intermediates such as the /Miydroxy-a-methylene-y-butyrolactones (e.g. 63)128 and tetrahydrochromanone derivative 64129. Interestingly, the facility and efficiency of this rearrangement has also attracted attention beyond the conventional boundaries of organic chemistry. Thus, a study on mechanism-based enzyme inactivation using an allyl sulfoxide-sulfenate rearrangement has also been published130 131. 

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

Danieli et al. 116), both of which utilize an alkylation process of 1-methyl-3,4-dihydro-(3-carboline (150) in the key ring-forming step. In the first one, treatment of 150 with a-methylene- y-butyrolactone gave enamide 172, which, when reduced with lithium aluminum hydride, afforded indolo[2,3-a]quinolizine derivative 173. The desired ethylidene substituent at C-20 has been developed from the hydroxyethyl side chain in a four-step sequence as shown below. 

An obvious way to target chiral compounds is to start with a compound in which the chiral center is already present. Here natural products and derivatives offer a rich pool of generally inexpensive starting materials. Examples include L-hydroxy and amino adds. Sometimes, just one out of many chiral centers is predestined to remain, as in the synthesis of vitamin C from D-glucose, or in the preparation of (S)-3-hydroxy-y-butyrolactone from ladose. 

In addition, other systems of nomenclature for AHLs have also appeared in the literature describing them as derivatives of furanone, y-butyrolactone or 4-butanolide. For example, the above V.fischeri autoinducer can also be named as (S)-N-(3-oxohexanoyl)-3-aminodihydro-2(3H)-furanone,(S)-a-(3-oxohexa-noyl)amino-y-butyrolactone or (S)-2-(3-oxohexanoyl)amino-4-butanolide (another IUPAC name) [27]. 

Triethylamine, 46, 18 dehydrobromination of oi-bromo-y-butyrolactone with, 45, 23 Triethyl phosphonoacetate, reaction of sodium derivative with cyclohexanone to yield ethyl cyclo-hexylideneacetate, 46, 45 Trifluoroacetic anhydride, 45, 98 Teiphenylalctminum, 46,107... 

Both enantiomers of the bicyclic enone 78 and their derivatives have been proved to be useful chiral building blocks for the synthesis of natural products [29], among them y-butyrolactones. 78 is readily available in either enantiomeric form by a Diels-Alder reaction of furan with a-acetoxyacry-lonitrile and subsequent hydrolysis, followed by a resolution of the racemate... 

Two classes of a-hydroxylated lignans have been enantioselectively prepared a) wikstromol (3) [10, 38] and related natural products [39] and b) gomisin A (1) and congeners [40, 41]. In both cases, chiral, non-racemic ita-conic acid derivatives have been synthesized as key compounds for the preparation of -benzyl-y-butyrolactones (either by resolution (g [32]) or by asymmetric hydrogenation (h [25])). 

Scheme 43 Pyranoside 2,3-fused-Y-butyrolactones from a glycal derived cyclopropane...

P)-(+)-Ethyl 4,4,4-trifluoro-3-hydroxybutyrate 4 derived from enzymatic resolution was transformed to (P) - (+) - y-trifluoromethyl- y-butyrolactone 42 which were elaborated to give the corresponding ( R)-(+)-y-trifluoromethyl-a-methylene-y-buty rolactone 43 [48]. 

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