Lactones asymmetric hydroformylation

Acetalization of oxo aldehydes is used to protect sensitive aldehyde products, especially in asymmetric hydroformylation preventing racemization of an a-chiral aldehyde product [18-22,27]. Acetal formation can also be applied to the synthesis of monocyclic or spirocyclic pyranes as potential precursors and building blocks for natural products such as pheromones or antibiotics. A representative example is the synthesis of the pyranone subunit of the Prelog-Djerassi lactone. For this purpose, various 1,2-disubstituted homoal-lylic alcohols were used (Scheme 3) [32],... 

Very efficient asymmetric hydroformylation of alkenes, dienes, and heterocycloalkenes is achieved with a complex formed by mixing RhCacacXCO) and 52. The diphosphines 53 and 54 have found utility in the preparation of y-lactones" from allylic alcohols and 3-substituted cyclopentanones " from 4-substituted 4-pentenals, respectively, and in chiral forms. 

Some heterocyclic systems such as tetrahydrofuxan, tetrahydropyran, thiophene, and pyrrolidine are foimd in a wide range of biologically active compounds. Hydroformylation of these heterocyclic olefins provides a potential synthetic route for the synthesis of these targets (Scheme 11) [93,94]. Asymmetric hydroformylation of a-methylene-y-butyrolactone using the cationic Rh(I)-(l )-BINAP complex as a catalyst is also reported to give an aldehydic lactone containing a quaternary chiral center in up to 37% ee [95]. 

The same authors reported about a short synthesis of the (+)-Prelog-Djerassi lactone benefiting from an asymmetric hydroformylation-crotylation one-pot reaction (Scheme 5.141) [30, 31]. The hydroformylation of vinyl 2,6,7-trioxabicyclo[2.2.2]octane was carried out with a (S,S,S)-BDP-based rhodium... 

Scheme 5.141 Synthesis of the (+)-Prelog-Djerassi lactone via an asymmetric hydroformylation-crotylation one pot reaction.

SCHEME 14.8. Asymmetric hydroformylation of A, A-diethylacrylamide gives products that are intermediates for synthesis of a lactonic proteasome inhibitor 3. 

SCHEME 14.19. Asymmetric hydroformylation of seven-membered cyclic unsaturated acetals gives a synthetically useful lactone. 

Hydroformylation with the BIPHEPHOS ligand is a slow process reqiiireing 5 days at 65°C to proceed. The domino hydroformylation allylboration hydroformylation sequence resulted in a mixture of anomeric lactols (48%). In order to facilitate product analysis this mixture was directly oxidized to the corresponding lactones 62 and 63 (63%). The diastereomeric lactones were obtained in a 1 1 ratio, (18) indicating that the asymmetric induction from the resident stereocenter is low. 

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