Butenolides chiral synthesis

The C14-C20 segment [83] The route adopted for the chiral synthesis of the C14-C20 segment followed their replicating lactone method [89, 90] starting from the same lactone 102 (Scheme 14). A standard five-step transformation of 102 provided the epoxide 109 on which a two-carbon extension sequence [89, 90] furnished the replicated butenolide 110. Conjugate addition of the bulky lithium m s(methylthio)methane followed by an enolate hydroxylation... 

A stereoselective osmylation approach was applied to the synthesis of C(l)—C(7) and C(7)—C(13) subunits of erythronolide A41. A key synthon of the erythronolide A seco acid, 30, was prepared in an enantiomerically pure form by utilizing a stereoselective osmylation of the chiral hydroxy (Z, )-diene ester 31 and subsequent hydrogenation of the resulting butenolide 32 (equation 24). 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

The experimental procedures given below for the synthesis of both enantiomers of 4-substituted butenolides [390] emphasize some aspects of the reactivity of chiral 0-ketosulfoxides their reduction with hydrides can... 

In the course of a total synthesis of aphidicolin (107), the conjugate addition of the dienoiate (104) to the chiral butenolide derivative (105) serves as a key step. A 7.4 1 mixture of diasteieomeric products is obtained, from which the major isomer (106) can be isolated in pure form after recrystaliization (Scheme 41).121 The selectivity of this remarkable reaction, in which two quaternary stereogenic centers are simultaneously generated in a highly selective manner, can be explained by the assumption that the reactants approach each other in the chelate-mode indicated in (108). 

For example, N-(2-hydroxyphenyl)imines 9 (R = alkyl, aryl) together with chiral zirconium catalysts generated in situ from binaphthol derived ligands were used for the asymmetric synthesis of a-amino nitriles [17], the diastereo- and/or enantioselective synthesis of homoallylic amines [18], the enantioselective synthesis of simple //-amino acid derivatives [19], the diastereo- and enantioselective preparation of a-hydroxy-//-amino acid derivatives [20] or aminoalkyl butenolides (aminoalkylation of triisopropylsilyloxyfurans, a vinylogous variant of the Mannich reaction) [21]. A good example for the potential of the general approach is the diastereo- and enantioselective synthesis of (2R,3S)-3-phenylisoserine hydrochloride (10)... 

The only report of 2-sulfinyl butenolides appeared in 1993 [50]. The synthesis of 5-ethoxy-3-p-tolylsulfinyl-2(5H)-furanones (42a and 42b) and their behavior as dienophiles in asymmetric Diels-Alder reactions with cyclopentadiene were studied. This paper evaluates the relative ability of the two chiral centers at the dienophile (sulfur and C-5) to control the stereochemical course of the reaction. From the results obtained it was concluded that both chiral centers have a... 

In planning the synthesis of a series of carbapyranoses in their chiral non racemic format, Zanardi and co-workers [7d] utilized the seven-carbon lactone 149, in turn prepared by elaboration of butenolide 12 (vide supra, Scheme 3). 

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

A few other examples are listed in Scheme 49 intramolecular addition of amine giving a good synthesis of (/ )-(-P)-camegine, synthesis of chiral butenolides by carbonation of vinylic carbanions and conjugate additions of cuprates yielding chiral chromans. ... 

Chiral 3-hydroxy sulfoxides are very good inteimediates for the synthesis of optically active alcohols, epoxides or butenolides (Scheme 59). ... 

The catalytic, enantioselective, vinylogous Mannich reaction has recently emerged as a very powerful tool in organic synthesis for the assembly of highly functionalized and optically enriched 6 amino carbonyl compounds. Two distinctly different strategies have been developed. The first approach calls for the reaction of preformed silyl dienolates as latent metal dienolates that react in a chiral Lewis acid or Bronsted acid catalyzed Mukaiyama type reaction with imines. Alternatively, unmodified CH acidic substrates such as a,a dicyanoalkenes or 7 butenolides were used in vinylo gous Mannich reactions that upon deprotonation with a basic residue in the catalytic system generate chiral dienolates in situ. 

---