Enantioselective hydroformylation of alkenes can simultaneously create a new C À C bond, install a very versatile functional group, and produces enantiomerically enriched compounds from very economic reagents: an alkene, carbon monoxide, and hydrogen. Given the precedent for large-scale production of achiral linear aldehydes, hydroformylation can be viewed as potentially the ideal reaction for commercial production of chiral building blocks.[1] However, there have been far more hurdles to overcome relative to core asymmetric production methods such as asymmetric hydrogenation, despite decades of research effort.After intensive research effort, a range of catalysts that give good enantiomeric excess (ee) for model substrates (e.g. styrene) are now available.[2] There is now substantial research and commercial interest in making products of relevance to the pharmaceutical industry and organic synthesis using this technology.[3] Despite all this activity, the control of regioselectivity towards the branched aldehyde is at best only a partially resolved issue. Certain well-known substrates like styrene give the branched aldehyde with a typical regioselectivity of around 10:1, which is usable after purification, although higher selectivity is desirable. Some functionalized substrates show a very high preference for the branched aldehyde with the correct choice of catalyst, and ligands that simultaneously act as reversible auxiliaries for the substrate and bind rhodium have been applied successfully to control regioselectivity for specific functionalized alkenes. [4] A completely unresolved issue that would represent a huge step forward is the controlled formation of branched chiral aldehydes from simple terminal alkyl olefins of type RCH 2 CH=CH 2 . Here we show the most significant progress yet towards this general goal, with the first catalytic reactions that combine significant regioselectivity and enantioselectivity for alkenes of type RCH 2 CH = CH 2 .We have had a long-standing interest in obtaining branched aldehydes from alkyl alkenes, but in the absence of any real leads have confined these efforts to screening novel catalysts that were originally designed to solve other problems in carbonylation catalysis. In one recent research project aimed at further tuning the excellent performance of the important asymmetric hydroformylation ligands, Kelliphite and Ph-bpe, we considered a hybrid non-symmetric ligand that would present the best of both these ligands, and might gain advantage from being non-C 2 symmetric. Phosphine-phosphites have attracted much interest in hydroformylation, [2g,l-q] although phospholano derivatives or derivatives using a ÀCH 2 OÀ backbone are not well studied.[2n,p] The ligand, that we have tended to refer to as bobphos ("best of both phosphorus ligands"), (S ax ,S,S)-4, can be produced reliably by the route shown in Scheme 1 from the known precursor 1.[5] The phosphite coupling was accomplished by activating (S)-2 with Me 3 SiI; this does not proceed cleanly and the ca. 40:60 mixture o...
