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Monday, July 20, 2009
Douglass F. Taber
University of Delaware

Enantioselective Synthesis of Alcohols and Amines

Enantiomerically-enriched alkoxy stannanes such as 3 are versatile intermediates for synthesis. John R. Falck of UT Southwestern found (Angew. Chem. Int. Ed. 2008, 47, 6586. ) that the simple combination of Bu3SnH and Et2Zn generated a reagent that added to aldehydes such as 1 under catalysis by the MIB amino alcohol introduced by Nugent (Chem. Commun. 1999, 1369. ) to give the adduct 3 in high ee. Gonzalo Blay and José R. Pedro of the Universitat de València showed (Chem. Commun. 2008, 4840. ) that it was possible to modulate the reactivity of the acidic 4, allowing catalyzed formation of the high ee adduct 5 to dominate. Xiaoming Feng of Sichuan University developed (J. Am. Chem. Soc. 2008, 130, 15770 ) an Ni catalyst for the intermolecular ene reaction of 6 with 7 to give 8 in high ee.

Enantioselective allylation is a key transformation in current organic synthesis. Yoshito Kishi of Harvard University optimized (Org. Lett. 2008, 10, 3073. ) enantioselective Cr-mediated allylation, with a ligand that can be easily recovered and recycled. Michael J. Krische of UT Austin devised (J. Am. Chem. Soc. 2008, 130, 14891. ) a ligand-catalyst combination for effecting the enantioselective allylation of alcohols such as 12. Brian M. Stoltz of Caltech developed (Angew. Chem. Int. Ed. 2008, 47, 6873. ) a protocol for the enantioselective allylation of the enol ether 15, leading to the construction of oxygenated quaternary centers. Adducts such as 11 and 17 are of interest, inter alia, as direct precursors, by elimination, of the corresponding alkynes.

Simon Blakey of Emory University designed (Angew. Chem. Int. Ed. 2008, 47, 6825. ) a Ru catalyst that mediated enantioselective intramolecular C-H amination, converting the simple alcohol derivative 18 into the versatile secondary amine 19 in high ee. We established (J. Org. Chem. 2008, 73, 9334. ) a procedure, based on diazo transfer followed by Rh-mediated intermolecular N-H insertion, for aminating menthyl esters and separating the product diastereomers. The menthyl group, easily removed (TFA) from 21, served as a useful reporter of ee, by 1H NMR of the upfield methyl doublets. Wolfgang Kroutil of the University of Graz found (Adv. Synth. Catal. 2008, 350, 2761. ) that ω-transaminases could effect the reductive amination of methyl ketones such as 22 in high ee. In many cases, either enantiomer of the amine could be prepared, depending on the transaminase used.

Li Deng of Brandeis University developed (Angew. Chem. Int. Ed. 2008, 47, 7710. ) a cinchona alkaloid derived catalyst for the enantioselective conjugate addition of 25 to enones. Manabu Node of Kyoto Pharmaceutical University reported (Org. Lett. 2008, 10, 2653. ) a related procedure for the addition of a recyclable enantiomerically-pure amine to α,β-unsaturated esters. Géraldine Masson and Jieping Zhu of CNRS Gif-sur-Yvette devised (J. Am. Chem. Soc. 2008, 130, 12596. ) a catalyst, also based on cinchona alkaloids, for the enantioselecitve aza Morita-Baylis-Hillman reaction, converting the imine 27 into 29 in substantial ee. Teck-Peng Loh of Nanyang Technological University designed (Org. Lett. 2008, 10, 2805. ) the enantiomerically- and diastereomerically-pure hydroxylamine 30. The initial adduct of 30 with the aldehyde 1 rearranged to deliver 31 in high ee and as a single geometric isomer.

D. F. Taber, Org. Chem. Highlights 2009, July 20.