Pantolactone acrylate

The simple homochiral adduct from Diels-Alder cycloaddition of (/ )-pantolactone acrylate ester with cyclopentaidiene was hydrolyzed and converted to the methyl ketone in 89% yield through addition of 3... 

Formation of cyclic acetals was also observed in the MBH reaction of aliphatic aldehydes with pantolactone acrylate 28. The more stable cis isomers 29 are formed predominantly, and mixed products 30 can be isolated by sequential addition of two different aldehydes (Scheme 1.14). However, benzaldehyde failed to give the cyclic adduct on reaction with the pantolactone ester under the same conditions electronic effects rather than steric hindrance... 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

Hansen and colleagues177 used (+)-pantolactone as a chiral auxiliary to achieve asymmetric induction in the first step toward their synthesis of d.v-perhydroisoq uinol inc 278. The titanium tetrachloride catalyzed reaction between 1,3-cyclohexadiene (275) and chiral acrylate 276 proceeded with high diastereofacial selectivity to give 277 (94% de) in 75% yield (equation 77). 

Prompted by the X-ray studies of the acryloyl lactate-TiCU complex (380a), commercially available pantolactone was chosen as an auxiliary aiming to facilitate entropically the formation of a seven-mem-bered titanium chelate (385). Indeed, using 0.1-0.75 mol equiv. of TiCU the acrylate and crotonate of (/ )-pantolactone (384) underwent smooth addition of cyclopentadiene, butadiene and isoprene to give adducts (386) and (387) in ratios of >93 <7 (Scheme 94, Table 24, entries a-d). Opposite product ratios were obtained using dienophiles (388) derived from (S)-pantolactone (entiy e) or (390) derived from the more readily available A -methyl-2-hydroxysuccinimide (entries f, g). The major products were purified by crystallization and saponified without epimerization (LiOH, THF/water, r.t.) to furnish the corresponding carboxylic acids. 

In close relation to the work on acrylates derived from lactate, pantolactone and 2,5-disubstituted pyrrolidines (vide infra), A -acryloylproline benzyl ester (391) has t n studied as a chiral dienophile... 

Interestingly, the Diels-Alder reaction of the acrylate of o-pantolactone and cyclopentadiene in the presence of 2 equiv. MAD results in high diastereoselectivity which is the opposite of that encountered with ordinary Lewis acids. The low-temperature NMR spectrum of the Lewis acid complex of the acrylate of D-pantolactone showed that an ordinary Lewis acid such as SnCU forms the chelate complex [O] (Sch. 132). In the 1 1 acrylate-MAD complex, structure [P], although predominant, seems to be in equilibrium with the minor complex [Q] with s-cis conformation this... 

We saw pantolactone 156 acting as a reagent in chapter 26. Here it esterifles an unsaturated acid to control a Diels-Alder reaction. It has two main advantages. It is easy to use on a large scale and it is easily removed from the product. The simple acrylate derivative 157 reacts with cyclopentadiene to give essentially pure (by HPLC) adduct 158 in 81% yield after two recrystallisations.20... 

Successful polymer supported stereoselective Diels-Alder reaction was performed using immobilized enantiopure 4-(3-hydroxy-4,4-dimethyl-2-oxopyrro-lidin-l-yl)benzoic acid 12 as a chiral auxiliary [15]. The corresponding resin-bound acrylate derivate has been applied as the dienophile 13. Preparation of the precursor started with the combination of pantolactone 10 and the sodium salt of 4-aminobenzoic acid. Conversion into the corresponding benzyl ester followed. The obtained racemate was esterified with (lS)-camphanic acid chloride to a dia-stereomeric mixture to gain the enantiopure compounds by chromatographic separation. After subsequent saponification of the camphanic acid moiety and hydrolysis of the benzyl ester the (R)-enantiomer 11 was coupled to Rink amide resin (Scheme 12.6). 

Diels-Alder reactions of cyclopentadiene with methyl acrylate [19], (-)-menthyl acrylate, or other chiral dienophiles [20-23] catalyzed by cation-exchanged KIO montmorillonites were thoroughly investigated by Mayoral and co-workers. The structures of the chiral dienophiles are depicted in Figure 1. Moderate diastereo-selectivities were obtained with (-)-menthyl acrylate (54 %) and (7 )-f -acryloyl-pantolactone (53 %) in reactions catalyzed by zinc(II)-exchanged KIO montmoril-lonite at —20 °C. 

Asymmetric Diels-Alder reactions. Single-sited coordination of chiral dienophiles (e.g., the acrylate of ti-pantolactone) confers diastereoselectivity to the cycloaddition. 

It is clear that a restricted orientation of the dienophile is crucial to the success of the asymmetric Diels-Alder reaction. A good method to lock the conformation is to use an auxiliary containing a carbonyl group, such that the two carbonyl groups of the dienophile can chelate to a Lewis acid. Thus, high levels of diastereofacial selectivity can be achieved in Diels-Alder reactions of the acrylates of ethyl lactate or of pantolactone, in the presence of the Lewis acid TICU (3.91). The adduct 124 is formed almost exclusively (93 7 ratio of diastereomers) using butadiene and the acrylate of (/f)-pantolactone and can be purified easily by crystallization. Simple hydrolysis gives enantiomerically pure carboxylic acid 125. In such chelated systems, the metal is co-ordinated anti to the alkene of the dienophile and the acrylate therefore adopts the s-cis conformation 126. 

Dipolar cycloadditions of nitrile imines with alkenes lead to 2-pyrazolines. Moderate select vities are observed in reactions with the acrylate of (/ )-pantolactone. 

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