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Monday, February 11, 2013
Tristan H. Lambert
Columbia University

Asymmetric C-Heteroatom Bond Formation

Tomislav Rovis at Colorado State University developed (Angew. Chem. Int. Ed. 2012, 51, 5904. ) an enantioselective catalytic cross-aza-benzoin reaction of aldehydes 1 and N-Boc imines 2. The useful α-amido ketone products 4 were configurationally stable under the reaction conditions. In the realm of asymmetric synthesis, few technologies have been as widely employed as the Ellman chiral sulfonamide auxiliary. Francisco Foubelo and Miguel Yus at the Universidad de Alicante in Spain have adapted (Chem. Commun. 2012, 48, 2543. ) this approach for the indium-mediated asymmetric allylation of ketimines 5, which furnished amines 6 with high diastereoselectivity.

There has been vigorous research in recent years into the use of NAD(P)H surrogates, especially Hantzsch esters, for biomimetic asymmetric hydrogenations. Yong-Gui Zhou at the Chinese Academy of Sciences showed (J. Am. Chem. Soc. 2012, 134, 2442. ) that 9,10-dihydrophenanthridine (10) can also serve as an effective "H2" donor for the asymmetric hydrogenation of imines, including 7. Notably, 10 is used catalytically, with regeneration occurring under mild conditions via Ru(II)-based hydrogenation of the phenanthridine 11.

A unique approach for asymmetric catalysis has been developed (Nature Chem. 2012, 4, 473. ) by Takashi Ooi at Nagoya University, who found that ion-paired complexes 14 could serve as effective chiral ligands in the Pd(II)-catalyzed allylation of α-nitrocarboxylates 12. The resulting products 13 are easily reduced to furnish α-amino acid derivatives.

Another novel catalytic platform has been employed (J. Am. Chem. Soc. 2012, 134, 7321. ) for the chiral resolution of 1,2-diols 15 by Kian L. Tan at Boston College. Using the concept of reversible covalent binding, the catalyst 16 was found to selectively silylate a secondary hydroxyl over a primary one, thus leading to the enantioenriched products 17 and 18. Scott E. Denmark at the University of Illinois has applied (Angew. Chem. Int. Ed. 2012, 51, 3236. ) his chiral Lewis base strategy to the enantioselective vinylogous aldol reaction of N-silyl vinylketene imines 19 to produce γ-hydroxy-α,β-unsaturated nitriles 22.

For the preparation of enantioenriched homopropargylic alcohols 25, the asymmetric addition of allenyl metal nucleophiles (e.g. 24) to aldehydes 23 provides a straightforward approach. Although numerous groups have reported methods to accomplish this goal, Leleti Rajender Reddy at Novartis in New Jersey has developed (Org. Lett. 2012, 14, 1142. ) what appears to be a particularly convenient procedure using the "TRIP" chiral phosphonic acid catalyst.

The generation of stereocenters bearing both boron and halide functionality, especially via hydrogenation, would seem to be a particularly challenging goal. Nevertheless, Zdenko Casar of Lek Pharmaceuticals in Slovenia has found (Angew. Chem. Int. Ed. 2012, 51, 1014. ) that an iridium catalyst involving ligand 28 can efficiently and enantioselectively hydrogenate chloroalkenyl boronic esters such as 26 to produce the stereogenic products 27, which are useful chiral building blocks.

For the preparation of enantioenriched halogen-bearing stereocenters, Géraldine Masson at the Gif-sur-Yvette reported (J. Am. Chem. Soc. 2012, 134, 10389. ) that chiral phosphoric acids (e.g TRIP) or the corresponding calcium salts catalyze the addition of NBS across enecarbamates 29 to produce vicinal haloamines 30 with high ee. Meanwhile, chiral copper catalysis was used (J. Am. Chem. Soc. 2012, 134, 9836. ) by Kazutaka Shibatomi at Toyohashi University of Technology for the enantioselective chlorination of active methine compounds such as 31. The resulting enantioenriched chlorides 32 can be converted to the corresponding amines 33 or sulfides 34 with complete stereospecificity.

T. H. Lambert, Org. Chem. Highlights 2013, February 11.