7-Butyrolactones, 2,4-disubstituted

The transformation proceeds with excellent stereoselectivity by kinetic formation of the 2,5-trans-disubstituted pyrrolidine 2-328 [182]. The tertiary amine can now initiate a nucleophilic backside displacement of the vicinal iodide in 2-328, leading to an aziridinium salt 2-329 [183]. This event ensures a net retention of the stereochemistry at C-13 in the following attack of the ester carbonyl in the butyrolactone ring closure to give 2-330. 

The reaction shown in Eq. 9.47 demonstrates a short synthesis ofy-[(trityloxy)methyl]-a-alkylidene-y-butyrolactones having stereodefmed mono- and disubstituted exo-alkylidene... 

Intriguingly, the enantiomeric trans-disubstituted y-butyrolactone (-)-75, completing a formal synthesis of (-)-methylenolactocin (11) [47], can be obtained by cyclizing 67 through an iodolactonization after protection of the free OH group (Scheme 11). 

The cyclopropane aldehyde 156 was identified as a versatile chiral building block for the enantioselective synthesis of 4,5 disubstituted y-butyrolactones of type 158 or 159. Both enantiomers of 156 can be easily obtained in a highly diastereo- and enantioselective manner from fixran-2-carboxylic ester 154 using an asymmetric copper-catalyzed cyclopropanation as the key step followed by an ozonolysis of the remaining double bond (Scheme 25) [63]. Addition of... 

One application of this catalytic generation of homoenolate type intermediates is in the stereoselective formation of y-butyrolactones 64 from a,/ -unsaturated aldehydes 62 and their reaction with aldehydes or ketones 63 [60]. (For experimental details see Chapter 14.19.2). Glorius [60a] and Bode [60b] almost simultaneously published their results utilizing a N-heterocyclic carbene generated from a bisar-ylimidazolium salt 65 (IMes). The corresponding disubstituted y-butyrolactones... 

Dirhodium(II) tetrakis(carboxamides), constructed with chiral 2-pyrroli-done-5-carboxylate esters so that the two nitrogen donor atoms on each rhodium are in a cis arrangement, represent a new class of chiral catalysts with broad applicability to enantioselective metal carbene transformations. Enantiomeric excesses greater than 90% have been achieved in intramolecular cyclopropanation reactions of allyl diazoacetates. In intermolecular cyclopropanation reactions with monosubsti-tuted olefins, the cis-disubstituted cyclopropane is formed with a higher enantiomeric excess than the trans isomer, and for cyclopropenation of 1-alkynes extraordinary selectivity has been achieved. Carbon-hydro-gen insertion reactions of diazoacetate esters that result in substituted y-butyrolactones occur in high yield and with enantiomeric excess as high as 90% with the use of these catalysts. Their design affords stabilization of the intermediate metal carbene and orientation of the carbene substituents for selectivity enhancement. 

Regioselective oxidation of 2- and 4-alkyl-l,4-hutanediols. 2,2-Disubstituted 1,4-butanediols (1) are oxidized by this combination -.electively to the 7-butyrolactones 2. Cobalt(II) alkanoates and trityl tetrafluoroborate show comparable selectivity. 

Iodolactonization of yfi-unsaturated amides. Halolactonization (I2 or NBS) of a-substituted "y,8-unsaturated amides in DME/H,0 at room temperature gives predominantly fra/w-2,4-disubstituted y-butyrolactones (equation I). This 1,3-stereoselectivity is in sharp contrast to the moderate 1,3-cw-selectivity observed with a-substituted y,8-unsaturated acids (8,257 9,248). Both diastereomers of a, 3-disubstituted y.S-unsaturated amides are converted into 2.4-rram-2,3,4-trisub tituted lactones (equation II). 

This is the smallest group of lignan tetrahydrofurans with fewer than ten members. All of reasonably well defined constitution are 3,4-trarw-disubstituted. Of these, most attention has been directed towards burseran, a constituent of Bursera microphylla with tumour-inhibiting properties (82). Optically pure (-)-/ra/w-burseran (82) and (-f-)-cw-burseran (83) were stereoselectively synthesized from chiral butyrolactones and gas chromatographic comparison indicated that the natural... 

Magnetic nonequivalence is not uncommon. The spin systems for both para- and ortho-disubstituted benzene rings are AA XX (or AA BB if the chemical shifts are close). Figure 4-3 illustrates the proton spectrum of 1,2-dichlorobenzene (4-8), which is AA XX and relatively complex. Constraints of a ring frequently convey magnetic nonequivalence, as, for example, in butyrolactone (4-9). Even open-chain systems such as... 

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). 

Butyrolactones. - A variety of ruthenium3 4 and rhodium hydride30 complexes have been tested for their suitability as dehydrogenation catalysts for the oxidation of 1,4-diols into butyrolactones. with 2-substituted and 2,2-disubstituted diols, the regioselectivity can be almost complete and the accompanying excellent yields make the overall transformation ((336) - (337) ] a genuinely viable proposition. 

Cw-Disubstituted butyrolactones (50) have been investigated less extensively than their /ra/i -counterparts. One attractive route to such compounds involves the diastereoselective opening of a cyclic meso-anhydride (49) (scheme 15) [67]. The required anhydride was prepared by a route involving two consecutive Stobbe condensations, leading to the doubly unsaturated anhydride (48). Differentiation of the two acyl groups of (49) was achieved by reaction with an enantiomerically pure primary amine. The monoacid monoamide was then converted into the required lactone (50). 

Finally, several recent syntheses involve the preparation of aP unsaturated lactones of the savinin or gadain type. Such compounds are readily prepared from the corresponding monobenzyl-butyrolactones by condensation (scheme 19). While elimination of the mesylate leads to the (Z)- somex [71], elimination of the acetate affords the j-isomer [72]. The (Z)-isomer (61) can be converted into (-)-savinin (62) in high yield by treatment with tributyltin hydride. Hydrogenation of (61) or (62) affords the cw-disubstituted lactones (63) (scheme 20) [73]. 

The a-(diphenylmethylsilyl) esters have been shown to be vinyl dication equivalents 3, and as such are precursors to terminal olefins and deuterated olefins, 1,1-disubstituted olefins and tri- and tetrasubstituted olefins. They are precursors to B-ketosilanes and ketones, wherein the overall transformation results in an ester to ketone conversion. They can also be deprotonated and the enolate anion condensed with aldehydes and ketones to give a,6-unsaturated esters, in particular a-alkylated-a,B-unsaturated esters. Their y-lactone counterparts, o-(diphenylmethy1snyl )-y-butyrolactone 4a and a-(diphenylmethylsilyl)-y-valerolactone 4b, are precursors to 4-oxo acids,1,4-diketones and a-ylidene-y-lactones. ... 

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