Ti-TADDOLate-catalyzed, highly enantioselective addition of alkyl- and aryl-titanum derivatives to aldehydes

Enantioselective Reduction of Diaryl Ketones Catalyzed by a Carbonyl Reductase from Sporobolomyces salmonicolor and its Mutant Enzymes

“…Rhodium-, titanium-and copper-catalyzed enantioselective aryl transfer reactions to aromatic aldehydes have also been reported and the corresponding arylmetal species have been proposed to be the active nucleophiles. [11][12][13] However, in many of the described processes, high catalyst loadings (10-20 mol%) and/or addition of additives such as polyethylene glycol ether (PEG) are required to achieve synthetically useful results, since achiral, non-catalytic background aryl addition often leads to a product of low enantiomeric purity. [1,14] An alternative approach to synthesize enantiomerically enriched diarylmethanols is the reduction of diaryl ketones, [1] which can be achieved chemically and biocatalytically.…”

A New Aspect of Magnesium Bromide‐Promoted Enantioselective Aryl Additions of Triaryl(tetrahydrofuran)aluminum to Ketones Catalyzed by a Titanium(IV) Catalyst of trans‐1,2‐Bis(hydroxycamphorsulfonylamino)cyclohexane

“…While keeping 4 at 5.0 equiv. and MgBr 2 at 24 mol% but tuning AlPh 3 A C H T U N G T R E N N U N G (THF) to 2.5 and 1.5 equiv., yields of the product decreased to 83% (84% ee, entry 11) and 23% (entry 12), respectively.…”

“…[2] Two synthetic protocols have been established for the synthesis of chiral diarylmethanols: (1) asymmetric reduction of ketones [3] and (2) asymmetric aryl additions to aldehydes. After the first phenyl additions reported by Seebach and a co-worker using the titanium-TADDOLate catalyst and the highly reactive PhTiA C H T U N G T R E N N U N G (O-iPr) 3 reagent, [4] various zinc catalytic systems using a variety of arylzinc reagents, such as ZnPh 2 , [5] mixtures of ZnEt 2 /ZnPh 2 , [6] reagents generated from heating ZnEt 2 and ArB(OH) 2 [2b,c,7] or other arylboron compounds, [8] and reagents from reactions of ZnCl 2 and aryllithium compounds, [9] have been demonstrated to induce excellent stereocontrol of diarylmethanols. In addition to the above-mentioned phenyltitanium and arylzinc reagents, a few examples of direct arylboron additions catalyzed by rhodium [10] or nickel [11] catalysts have also been demonstrated.…”

“…We surprisingly found that inorganic salts such as MgBr 2 and MgI 2 were essential in promoting the addition reactions affording tertiary alcohols in high yields and excellent enantioselectivities. 4 , which is the best performing condition for asymmetric AlEt 3 additions to aldehydes catalyzed by the titanium catalyst of N-sulfonylated amino alcoholate, [28] the AlPh 3 A C H T U N G T R E N N U N G (THF) addition reaction proceeded sluggishly affording the tertiary alcohol in only a 21% yield (entry 1) in a reaction time of 12 h. We then searched for reasons for the slow reaction of the titanium catalyst of 2 employing the AlPh 3 A C H T U N G T R E N N U N G (THF) reagent, and in one occasion, the reaction using an impure sample of AlPh 3 A C H T U N G T R E N N U N G (THF) gave the tertiary alcohol in quantitative yield and a good 88% ee (entry 2). Since AlPh 3 A C H T U N G T R E N N U N G (THF) was prepared from a reaction of AlCl 3 and phenylGrignard reagent in THF, the impure sample likely contained a trace amount of magnesium halide, which might play a key role in the promotion of the asymmetric catalytic reaction.…”

Arene-promoted lithiation of 1,n-dihaloalkanes (n=2–6): a comparative study

“…The best yields of 1,4-, 1,6-, 1,7-and 1,8-diols 4 were obtained from dichloroalkanes 3a (n = 2, 4, 5 and 6). The preparation of 1-chloro-4-lithiobutane 14 (2, n = 4, X = Cl) and 1-chloro-6-lithiobutane 15 (2, n = n, X = Cl) by monolithiation of the corresponding n-chloro-1-iodoalkanes with butyllithium have been previously reported. …”