Optically Active y-Lactones

Unique aqueous electrolysis media have been developed and highly efficient electrochemical oxidations of alcohols were accomplished using these systems. Tanaka s group developed the anodic oxidation of alcohols mediated by N-oxyl in an aqueous silica gel disperse system (Figure 12.6) [18]. The system could be successfully applied to the kinetic resolution of sec-alcohols and the enantioselective oxidation of meso-l,4-diols, affording optically active y-lactones (Scheme 12.3). 

Watanabe, S. Sakai, Y. Takeda, M. Kitazume, T. Yamazaki, T. Synthesis of optically active y-lactones and dopants for ferroelectric liquid crystals possessing a trifluoromethyl group. J. Fluorine Chem. 1994, 67, 149-152. 

Carene via the key intermediate 213 can alternatively be converted in an essentially one-pot reaction pathway to the optically active y-lactone 215 [397] intended to be a precursor for optically active 1-R-cis-permethrin 216 [398]. 

Dimethoxyoxetanes.1 In the presence of ZnCl2, this ketal reacts with 0-hydroxy aldehydes to give 2,2-dimethoxyoxetanes, which can be converted into 4-hydroxy-3-methyl-8-lactones and 5,6-dihydro-2-pyrones. In one case, an optically active lactone was obtained in 80% ee from an optically active y-hydroxy aldehyde. 

An important group of cyclic dienophiles are butenolides. Optically active y-substituted butenolides can be prepared from naturally occurring chiral compounds, such as D-mannitol [(5)-5-hy-droxy-2-penten-4-olidc]18, D-ribonolactone [(5)-5-hydroxy-2-penten-4-olide and its derivatives]19 or L-tartaric acid [(5)-2-penten-4-olide known as /i-angelica lactone]20. Chiral butenolides are extremely selective dienophiles in thermal [4 + 2] cycloadditions to acyclic dienes. 

Optically active 3-lactones are readih p using 72 as the chirality inducer. - - The p acids. The [2 -f 2]cycloaddition of ketenes ai nine leads to numerous c y-2,3-disubstituted f Reports on the advances of asymmetric 1 of diazoalkanes to A-(2-alkenoyl)oxazolidin-. 73, showing cooperative chiral control by the ral ligand.An intramolecular cycloaddition a chiral cyclic A,N -dimethylaminal unit ad>i 74) proves very successful in the asymmetric nitrone lacks stereoselectivity, - ... 

The mechanisms of the regioselectivity and stereochemistry of the ring-opening reactions of y3-butyrolactones by activated anions has been reviewed. A study of the mechanism of hydrolysis of y3-propiolactone has been reported. A mechanistic appraisal of diastereoselective and enantioselective syntheses of optically active j8-lactones has been made. An ab initio study on the thermal decomposition of y-butyrolactone has shown that decarbonylation is easier energetically than decarboxylation. ... 

Further examples of reagents and methods for asymmetric reduction are provided by the complexes obtained by partial decomposition of LiAlH4 by AT-methylephedrine(85) and either AT-ethylaniline" or 3,5-dimethylphenol. The first of these reduces open chain enones to allylic alcohols with enantiomeric excesses approaching 100%, whereas the second has been used to reduce conjugated acetylenic ketones to propargylic alcohols en route to optically pure y-lactones. Enantiomeric excesses of up to 90% are also obtained in the reduction of acetylenic ketones and acetophenones with LiAlH4 complexed with several optically active 1,3-amino-alcohols,and the chiral LiAlH4-derivatives (86) reduce ketones in up to 87% optical yield. ... 

The addition of the dianion of /j-sulfmylcarboxylic acids to carbonyl compounds leads to the formation of the corresponding hydroxy derivatives which undergo spontaneous eyclization to give y-lactones. It was found that when optically active ( + )-(/ )-3-(4-methylphenylsulfinyl)pro-panoic acid is used for the reaction, the corresponding diastereomeric /i-sulfinyl-y-lactones are formed in a ratio which is dependent on the substituents of the carbonyl component. However, the diastereoselectivity was always moderate. 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

The a-acetylenic alcohols were used in a synthesis of optically active 4-alkyl- y-lactones (80) (90), as shown in Scheme 11. Lactones with optical purity >... 

Compound 58 was isolated as a yellow crystalline, optically active compound. HREIMS data for 58 gave a molecular formula of C15H16O4 with an inherent eight degrees of unsaturation. The IR spectrum was consistent with the presence of conjugated carbonyl functionalities including a y-lactone (1779 cm ) and a conjugated ketone (1665 cm ). The... 

When employing enantioenriched l-titano-2-alkenyl carbamates 334 in carbonyl addition, the selectivity depends on the enantiomeric purity that was achieved in its preparation (see Section IV.C.l). The (ii)-crotyl derivative (R)-334a has been employed several times (equation 92)224,252,253 optically active homoaldol products 346 are easily converted into y-lactones 347 by four different pathways, which require an oxidation step (see Section IV.C.6). Appfications in target synthesis include the natural products (-b)-quercus... 

This asymmetric reduction has been used for synthesis of optically active 4-alkyl-y-lactones (equation l).4... 

Y. Watanabe, M. Milani, and S. Ozaki, Synthesis of optically active inositol derivatives starting from D-glucurono-6,3-lactone, Chem. Lett. 123 (1987). 

Enantioselective lactonization.5 Monoprotonation of the disodium salt (1) of 4-hydroxypimelic acid in ethanol results in cyclization to a y-lactone (2) in high yield. If 1 equiv. of (1S)-CSA is used optically active 2 is formed in yields as high... 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

PPL suspended in dry ether catalyzes the lactonization of a number of y-hydroxy acids. For example, f. V)-7 11 itt livlbut vn >lact one [19041-15-7] (R = CH, R = H, n = 1), and y-phenylbutyrolactone (R = C6H5, R = H, n = 1) may be produced in nearly quantitative yields (87-89). When prochiral derivatives (70) of y-hydroxypimelic acid were submitted to the action of PPL and Pseudomonasfluorescens Upases, optically active lactones with up to 98% ee were produced. 

A new and efficient method for the synthesis of optically active esters and lactones having a tertiary or a quaternary stereogenic centre at the y -position has been developed.28 Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides having two different substituents at the 2-position with the lithium enolate of t -butyl acetate gave optically active adducts in 99% chiral induction from the sulfur stereogenic centre. 

The Mannich adducts are readily transformed to optically active a-amino-y-lac-tones via a one-pot diastereoselective reduction and lactonization sequence and the tosyl group exchanged for a Boc group via a two-step procedure. The cop-per(II) ion is crucial for the success of this reaction [21]. It has the properties necessary both to generate the enol species in situ and, in combination with the C2-symmetric ligand, coordinate it as well as the imine in a bidentate fashion. The reaction proceeds via a cyclohexane-like transition state with the R substituent of the enol in the less sterically crowded equatorial position, which is required to obtain the observed diastereoselectivity (Fig. 5). 

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. 

Prochiral y-hydroxy diesters underwent enantioselective lactonization with PPL to afford the (S)-lactone in a highly enantioselective fashion (eq 17). Formation of macrocyclic lactones by the condensation of diacids or diesters with diols, leading to mono- and dilactones, linear oligomeric esters, or high molecular weight optically active polymers, depending upon type of substrates as well as reaction conditions, has also been described. 

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