Lactones panto

Fig. 14.3 Predictive models for asymmetric induction by (a) (R)-panto-lactone as a chiral auxiliary (b) (S)-prolinate dirhodium catalysts...

Reduction of ketopantolactone to D-pantolactone (0 in Fig. 8). This reaction is catalyzed by conjugated polyketone reductase. About 50 or 90 g/1 of D-panto-lactone (98 or 94% e.e., respectively) was produced with a molar yield of nearly 100% on incubation with washed cells of R. minuta or C. parapsilosis, respectively [115, 116]. 

Enantiomeric separations of bicyclic acid anhydride 69, lactones 70 and 71 and carboximides 72 and 73 by complexation with la-c in organic solvents were also successful (Table 3.3-3) [26]. These complexations can probably be carried out in a water suspension medium and hence be described as green processes. rac-Panto-lactone (74) was separated to produce (S)-(-)-74 of 99% ee in 30% yield by complexation with Ic [27]. Enantiomerically impure monoterpenes were purified by inclusion complexation with a chiral host compound. For example, (lS,5S)-(-)-verbe-none (75a) of 78% ee gave 99% ee enantiomer by complexation with la. By similar treatment of 75b of 91% ee with la as above, (lR,5R)-(-i-)-75b of 98% ee was obtained [28]. 

Panto- tbensaure Pantolacton + 0-Alanin Panto- lacton P-Alanin 0... 

J -(-)-2-Hydroxy-3,3-dimethyl -butyrolactone (3-hydroxy-4,4-dimethyl-4,5-dihydrofuran-2-one, D-panto-lactone) [599-04-2] M 130.1, m 89-91°, 90.5-91.5°, 91°, 92-93°, b 120-122°/15mm, [o] -28° (c 5, MeOH), [a] -51° (c 3, H2O). Recrystallise the lactone from Et20/petroleum ether, diisopropyl ether or C6H6/petroleum ether and sublime it at 25°/0.0001mm. It hydrolyses readily to the hydroxy-acid and racemises when heated above 145°. The Brucine salt has m 211-212° (from EtOH). [Kuhn Wieland Chem Ber 73 1134 1940, and Stiller et al. J Am Chem Soc 62 1779 1940, Bental Tishler Jriw Chem Soc 68 1463 1946, Beilstein 18/1 V 22.1... 

The ketene 25g prepared by dehydrochlorination has been produced on an industrial scale and gives a highly stereoselective reaction with R-panto-lactone forming the product ester in 64% yield (Eqn (4.11)). Related chiral 2-arylacetic acid derivatives have important pharmaceutical appHca-tions, of which ibuprofen, now sold as Advil, and naproxen, now sold as Aleve, are synthesized by this general route.Stereoselective additions to ketenes of appropriate chiral alcohols provide usefiil routes to the particular enantiomers needed for pharmaceutical application. 

Similarly, 2,4-dihydroxy-3,3-dimethylbutyrolactone known as D-(-)-panto-lactone 97 is used as chiral auxiliary along with TiCU in several D-A reactions. For example, the reaction of 2,3-dimethylbutadiene with a-cyanocinnamic acid affords the product of 92 % diastereomeric excess. 

Another chiral auxiliary-based approach was documented by Davies (Equation 5) [8, 34]. These studies involved diazo compounds that incorporate vinyl and C=0 substitution and revealed that these stable carbene precursors participate in a variety of useful transformations, including diastereoselective cydopropanations. Importantly, Davies found that the cydopropanations with 33, in contrast with those of their simpler diazoacetate counterparts, are highly diastereoselective. The reaction with styrene and chiral diazo compound 33 is representative treatment of styrene with 33 in the presence of a simple Rh catalyst resulted in the formation of product 34 with high asymmetric induction dr 98.5 1.5) and in 84% yield. In this example, the panto-lactone auxiliaiy is a convenient, readily available chiral alcohol. 

---