Asymmetric butenolides

Scheme 40.31 Proposed catalytic cycle for the asymmetric butenolide isomerization.

One of the earliest and most important discoveries in metal-catalyzed asymmetric synthesis is Sharpless s Ti-catalyzed epoxidation of allylic alcohols. A mere mention of all the total syntheses that have used this technology would require a separate review article Here, we select Trost s masterful total synthesis of solamin (100, Scheme 14), for its beautiful and multiple use of Sharpless s asymmetric epoxidation.1161 Optically pure epoxy alcohol 95 is converted to both epoxy iodide 96 and diol 97 The latter two intermediates are then united to give 98, which is oxidized and converted to dihydrofuran 99 by a Ramberg-Backlund transformation. The Re catalyzed butenolide annulation that is used to afford the requisite unsaturated lactone only adds to the efficiency of this beautiful total synthesis. 

Thus, 1.7-octadiene (79), which was subjected to monohydroboration followed by asymmetric dihydroxylation of the remaining double bond to give triol 80 with approximately 80% ee. Further transformations then afforded the desired butenolide 81. Double asymmetric dihydroxylation of diene 83 and subsequent protection gave hydroxy lactone 84 [98], which was then converted into acetylenic bis(hydroxy)bistetrahydrofuran 82 as the required intermediate for the (+)-asimicin synthesis. Mitsunobu inversion at C-24 gave rise to the diastereomeric (+)-bullatacin precursor. 

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)... 

In 2006, Hoveyda and coworkers developed an asymmetric Mannich reaction of silyloxyfurans and aldimines using a similar catalyst system (Scheme 9.18).28 The diastereo- and enantioselective reaction between silyloxyfurans and aldimines in the presence of catalyst gave y-butenolides, which are useful building blocks for organic synthesis. They also reported a mechanistic study of this reaction.2811... 

Under similar conditions, the same authors were able to control two stereogenic centers in an asymmetric vinylogous Mannich reaction. Indeed, treatment of imines derived from aryl a-ketoesters with siloxyfuran under related conditions gave functionalized y-butenolides with high diastereo- and enantioselectivities (Scheme 10.21 ).40... 

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... 

Full details for the palladium-catalyzed cyclization of 3,4-alkadienoic acids to 7-methylene-A -butenolides have been given (Equation 49) <2005T9896>. a-Substituted 7-alkylidene A -butenolides are also available in good yield by palladium-catalyzed carbonylative cyclization of /3-iodo enones <2005TL8137>. In asymmetric de novo syntheses of D- and L-talose, iterative asymmetric dihydroxylation reactions of dienoates have been employed to furnish 7-substituted A -butenolides <2005JOC10576>. 

Quite recently, Tiecco [46a, 128] reported the asymmetric version of the one-pot conversion of, y-unsaturated esters and nitriles 261 (Scheme 42) into the enantiomerically enriched allylic ethers and alcohols 276 (Scheme 45). The reactions were effected with the selenenyl sulfate produced from the camphor diselenide 26. Unfortunately, in the present case, this diselenide must be employed in stoichiometric amounts. However, it can be partially recovered at the end of the reaction. Good chemical yields and enantiomeric excesses (up to 86%) were obtained in the methoxyselenenylation-elimination reactions. Lower ee was observed when the reactions were run in ethylene glycol or in water. In the case of the hydroxyselenenylations, reaction yields were low because the addition products 275 gave rise to the lactones, which were then deselenenylated to the butenolides. These were isolated in about 30% yield. 

Trimethylsilyloxy)furan can also be used as a functionalized silyl enol ether for the asymmetric catalytic aldol-type reaction. Figadere has reported that the reaction of aliphatic aldehydes with the siloxyfuran catalyzed by BINOL-derived titanium complex provides the diastereomeric mixtures with high enantioselectivity (Sch. 42) [107], The addition reaction proceeds at the y position of the siloxyfuran to give butenolides of biological and synthetic importance. 

Sulfide has also been involved in a new two-step annulation method which featured stereospecific formation of three contiguous asymmetric centers. It was found that the lithium dienolate of the vinyl-ogous ester (6a) reacts rapidly with the a-thiophenyl butenolide (6b) to provide the corresponding adduct as a single diastereoisomer. Subsequent addition of vinyllithium, acidification and cyclization gave the tricyclic lactone (Scheme 30). 

The asymmetric dihydroxylation followed by internal lactonization has been used by Sato and coworkers [101] in their efficient preparation of enantiomeri-cally pure butenolides and furans (Scheme 26). AD of enyne 68 using AD-mix-p, afforded diol 69 in 74% yield and 97% ee. Hydromagnesiation generated the vi-... 

Sharpless asymmetric dihydroxylation of an alkenyl butenolide derivative. 

The isolation of the bfr-butenolide (38) from a new species of Eremophila provides a likely precursor of freelingnite and freelingyne (35). Its structure was deduced from spectroscopic data, the stereochemistry of the double bond at C-6 being inferred from the well known shielding effect on a methyl carbon by a yn-alkyl group. The configuration of the single asymmetric carbon was... 

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