Chiral auxiliary also pantolactone

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. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

Use as a Chiral Auxiliary. (5)-Ethyl lactate has been used as a chiral auxiliary in a variety of simple Diels-Alder reactions. As the fumaric acid diester, the de employing cyclopentadiene can almost be completely reversed by addition of Titanium(IV) Chloride (eq 8). In general, superior de values are achieved using (R)-Pantolactone in this context, and also for base-mediated addition to ketenes. ... 

Other types of functionalized enantiopure alcohols also make good chiral auxiliaries. Esters of commercially available methyl or ethyl (S)-lactates 1.15 [156] and (i )-pantolactone 1.16 [157, 158] are popular. The (5)-hydroxysuccinimide derivative 1.17, easily obtained from (S)-malic acid [158], provides access to the enantiomers of the products formed in the reactions of (f )-pantolactone 1.16. 

Exceptional are cyciopropanations with phenylethenyl-substituted diazoacetate 6 bearing a (R)-pantolactone unit as chiral auxiliary. The optimized rhodium(II)-catalyzed reaction of this diazo compound with phenylethene provides the cyclopropanecarboxylate 7 with a d.r. of 98.5 1.5. Recrystallization affords diastereomerically pure 7 which can be transformed into the enantiomerically pure (1 /< .2R )-1-amino-2-phenylcyclopropane carboxylic acid. Use of the corresponding (S)-lactates allows entry into the enantiomeric series105. This method was also applied to the enantioselective preparation of tropanes106... 

Mechanistic implications of these reactions and the structure of the active rhodium species have been discussed110. The effect of double stereodifferentiation is also known, when this catalyst and chiral diazoacetates with auxiliaries such as (-tf)-pantolactone are employed111. The most effective (/ )- or (S)-5-oxopyrrolidine-2-carhoxylate ligand has also been compared with other chiral cyclic ligands, which generally provide cyclopropanes in lower enantioselectivities 112 this type of complex can be bound to polyethylene113. The enantioselectivities of inter-and intramolecular cyclopropanations are apparently the same as with the free" complexes. 

Mark6 and co-workers also have explored the use of chiral derivatives of 2-pyrones to induce asymmetry. Chiral pyrones 66-69 were studied in their reactions with ethyl vinyl ether. As the data in Table 9 indicate, the pantolactone auxiliary is the most useful of those studied. Most intriguing is the fact that catalysis with either antipode of the europium Lewis acid, or even an achiral europium Lewis acid, yields the same stereochemically impressive results. 

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