Structure Investigation of Ti^IV‐BODOLates Involved in the Catalytic Asymmetric Reduction of Ketones Using Catecholborane

Abstract

The complexes formed by the reaction of [Ti(OiPr)(4)] and bicyclo-octanediols (BODOLs) 1 and 2 (1:1) are useful as chiral catalysts in asymmetric reductions and were investigated by (1)H NMR spectroscopy and computational methods. A consistent picture emerged of head-to-tail dimers being kept together via a Ti-O-Ti-O micro-oxo bridge similar to the Ti-tartrates but different from the corresponding Ti-BINOLates and Ti-TADDOLates.

Bicyclo[2.2.2]octane-derived chiral ligands—synthesis and application of BODOLs in the asymmetric reduction of acetophenone with catecholborane

“…24 Investigations of 1:1 mixtures of 4b and Ti(OiPr) 4 with NMR spectroscopy showed that several complexes were formed, in contrast to the single complex that was formed when employing 4a or 3g, respectively. 23 However, the introduction of a methyl group at the 4-position (4c, entry 1O) gave results comparable to 4a, implying that this may be a good attachment point for covalent anchoring of the ligands on solid support.…”

“…Amongst those reported are the aluminium complexes of the menthone and isomenthone-derived 1,3-diols, which were successfully applied to the asymmetric Diels-Alder reaction of 3-crotonoyl-2-oxazolidinone and cyclopentadiene 19 and to the Mukaiyama aldol reaction of the TMS enol ether of methyl isobutyrate and isobutyraldehyde, 20 respectively. Several bicyclo [2.2.2]octane-diol (BODOL) ligands have been reported to work as efficient asymmetric catalysts in the titanium catalyzed catecholborane (CBH) reduction of ketones [21][22][23] and in the diethylzinc addition to aromatic aldehydes. 24 In previous work, the ligands were synthesized by a multi-step procedure involving a bulky silyl protecting group for control of the stereoselectivity ('old route', Scheme 1).…”

Asymmetric baker’s yeast reductions of bridgehead-substituted bicyclo[2.2.2]octane-2,6-dione derivatives followed by conversion into catalytically active BODOLs for the diethylzinc addition to benzaldehyde

“…16,17,[20][21][22] For the asymmetric diethylzinc addition, most satisfactory results were obtained with BODOLs bearing an o-anisyl substituent at the 2-position (89%, 92% ee). Thus, we decided to transform optically active hydroxy ketones (À)-19 and (À)-22 into 2-o-anisyl BODOLs and investigate their catalytic capacity in the asymmetric diethylzinc addition (Scheme 6).…”

“…[16][17][18][19][20][21][22][23][24][25] New applications for bicyclo [2.2.2]octanes are presented continuously. Recently, Baran et al reported the synthesis of polyhydroxylated bicyclic systems, which exhibited enzyme-specific inhibition against a-glycosidase.…”

“…29,30 Several examples exist where optically active hydroxy bicyclo [2.2.2]octanones serve as important chiral building blocks in the synthesis of bioactive natural products. 9,[31][32][33] The development of bicyclo [2.2.2]octane derivatives, to be used as ligands 17,18,20,23,24,[34][35][36][37][38] and scaffolds in natural product mimetics, 39,40 is an ongoing project in our laboratories. Recently, we published two synthetic routes towards novel bridgehead hydroxy bicyclo [2.2.2]octane-2,6-dione 9 (Scheme 1).…”