Dienes asymmetric hydroformylation

The asymmetric hydroformylation of a 1,3-diene has been recently used in the course of a total synthesis of the antifungal natural product ambruticin. The retrosynthesis as well as the hydroformylation key step are depicted in Scheme 25 [75]. 

Asymmetric hydroformylation of conjugated dienes has been almost unexplored. Recently, however, promising results were reported when Rh(acac)(CO)2/(E,5)-BINAPHOS (6) is used as the catalyst. Reactions give the corresponding p,y-unsaturated aldehydes with high enan-tiopurity (<96% ee) and regioselectivity (78-95% branched) (Scheme 7.5) [20,81],... 

Asymmetric hydroformylation." Optically active aldehydes can be obtained by hydroformylation (CO/H2 = 1 1) of conjugated dienes with HRhfCOjCPfCaHsljjj-(-)-DIOP as catalyst. The highest optical yield (32%) was obtained in the hydroformylation of isoprene to give 3-methylpentanal. 

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. 

While hydroformylation of 1,3-butadiene has been intensively studied for the purpose of obtaining adipic acid [84,85], asymmetric hydroformylation of conjugated dienes has remained almost unexplored. A highly selective asymmetric hydroformylation of 1,3-dienes was reported using Rh(acac)[(i ,S)-BINAPHOS] as catalyst to give optically active p,y-unsaturated aldehydes (Scheme 9) [86,87]. 

The results of asymmetric hydroformylation are described here for individual substrate types such as normal open chain and cyclic alkenes, styrene and other alkenylaromatics, dienes, functionalized alkenes and alkynes. Earlier extensive compilations of results concerning this subject are found in several monographs and reviews31 45,54,104,105, l21,177,178,180,, 81. 

In 2013, Wong and Landis [26] investigated an asymmetric hydroformylation-(Wittig olefination) reaction of vinyl acetate by using a chiral catalyst based on (S,S,S)-BDP at 10bar (Scheme 5.136). After optimization, several other functionalized and nonfunctionalized olefins or 1,3-dienes could be converted under these conditions. 

FIGURE 14.3. Some of the conjugated dienes that have been successfully subjected to asymmetric hydroformylation. 

Based on these results, asymmetric induction in the hydroformylation of conjugated dienes is interpreted to arise from secondary hydrogenation of the primary achiral unsaturated aldehyde. Thus (at least in the above case), enantioface-discriminating hydrogenation of an unsaturated aldehyde (which is easily formed) and not enantiofacc discriminating hydroformylation of the primary diene or an intermediate alkene is responsible for asymmetric induction18-45. 

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