Asymmetric Hydrogenations (Nobel Lecture 2001)

Abstract

For Abstract see ChemInform Abstract in Full Text.

Bidirectional Metalation of Hydrobenzoin: Direct Access to New Chiral Ligands and Auxiliaries

“…They assumed that these pincer structures would impart a greater stability and also increase the reactivity of the catalyst through Lewis base activation of the metal. 26 In this study, the best results were obtained by using Yb(OTf) 3 and ligand 96 with 20% catalyst loading (97% yield of 93a and 94a, e.r. = 1.6:1).…”

“…Interestingly, Figure 11 shows that slow removal of the first ortho proton is followed by a relatively fast removal of the second proton to generate the tetraanion 142. Unfortunately, 3 Li and 1 H spectroscopy did not allow for additional insight into the nature and aggregation of intermediates involved in the production of the intermediate 142. Although further studies regarding the stoichiometry and rate of the reaction are needed to conclusively comment on the mechanism, it is possible to construct some hypotheses in this regard.…”

“…This conformational proclivity was rationalized by the selective complexation of BF 3 •OEt 2 to one of the oxygens of the hydrobenzoin acetal prior to reaction with the phenyl copper reagent. In their efforts directed towards the synthesis of the immunosuppressant natural product FK-506, Marshall and Xie reported a diastereoselective DielsAlder reaction using (R,R)-hydrobenzoin as a chiral auxiliary (Scheme 10).…”

“…2 Thus, over the past 30 years, the development of highly efficient, practical and enantioselective synthetic processes has been the focus of many researchers and recently the subject of the Nobel Prize in chemistry. 3 The most common method for introducing asymmetry in a synthetic process involves the use of chiral auxiliaries, which bias an otherwise non-selective reaction towards the formation of one diastereomer. As indicated below in Scheme 1, removal of the chiral auxiliary then unveils an optically pure product and oftentimes the chiral auxiliary itself can be recycled to improve the economics of the process.…”

“…14 In this work, (S,S)-hydrobenzoin 25 was converted into the stannylene acetal 44, which displaced the bromine atom in cis- The stereoselective addition of organocopper reagents to allylic acetals derived from (R,R)-hydrobenzoin has also been reported. 15 As indicated in Scheme 9, a phenyl copper reagent was added to the acetals 50-52 in the presence of BF 3 •OEt 2 to afford enol ethers derived from S N 2' or S N 2" additions.…”