Sulfoximines – Auxiliaries
Based on a serendipitous discovery at the beginning of the 90ies we developed a method to prepare enantiomerically pure allylic sulfoximines 2. Later, we used this building blocks to synthesize highly substituted hetero(poly)cyclic ringsystems 1 via a diastereoselective γ-hydroxyalkylation with (chiral), heteroatom substituted aldehydes 3, followed by a Michael addition.
Key intermediate is the cyclic sulfonimidate 4 whose stereogenic centers are defined by the choice of the amino acid (here: valine) folloewd by a separation of the S-epimers. In case of the lk-configured diastereomers, we developed a dynamic diastereomer differentiating cyclisation reaction which enables us to prepare enantiomerically pure R,R-4 and S,S-4 on a larger scale (more than 100g).
Two procedures to remove the auxiliary have been developed. On the one hand by the application of aluminum amalgame, lithium naphthalenide or samarium(II)-iodide it is possible to effect a methylenating desulfurization (not shown). On the other hand, reaction of the α-deprotonated sulfoximine with a carbenoid generates a species which, via β-elimination, delivers a sulfur free, angular vinylated product.