P-Hydroxy sulfoximines

Scheme 10.55 Borane reductions of ketones with p-hydroxy sulfoximine ligand.

In order to avoid the use of a rather expensive and potentially dangerous borane complex, Bolm et al. have developed an improved procedure for the borane reduction of ketones, which involved two inexpensive reagents namely NaBH4 and TMSCI. The reduction of a series of ketones was examined applying these novel reaction conditions and the same p-hydroxy sulfoximine ligand to that described above (Scheme 10.56). For most ketones, both the level of asymmetric induction and the yield compared favorably to the precedent results. 

In 1994, the scope of this p-hydroxy sulfoximine ligand was extended to the borane reduction of ketimine derivatives by these workers. The corresponding chiral amines were formed with enantioselectivities of up to 72% ee, as shown in Scheme 10.57. It was found that the A -substituent of the ketimine had a major influence on the asymmetric induction, with a ketoxime thioether (SPh) being the most successful substrate. 

Scheme 10.57 Borane reductions of ketimine derivatives with P-hydroxy sulfoximine ligand.

Addition to ketones. In 1982, Johnson and Stark31 reported the condensation reactions of (+)-(S)-Af,5-dimethyl-S-phenylsulfoximine (2a) with various aldehydes and prochiral ketones. The reaction of lithiated 2a with phenyl aryl ketones (PhCOR, R=Me, Et, n-Pr, n-Bu, and c-C6Hn) gave a mixture of two diastereomeric P-hydroxy sulfoximine adducts 54 with modest diastereoselectivity. Unfortunately, the diastereoselectivities of all of these reactions were not documented. 

P-Hydroxy sulfoximines are thermally labile and revert to their starting carbonyl compound and sulfoximine on mild thermolysis. This property has been exploited effectively as a method for the resolution of racemic chiral cyclic ketones.65 For example, the addition of the lithium salt of (+)-(S)-2b (99% ee) under kinetically controlled conditions (-78 °C) to racemic menthone gave three of the four possible diastereomeric adducts. The major two adducts resulted from attack on the menthone from the equatorial direction. These diastereomeric adducts could be readily separated by column chromatography. Thermolysis of the individual two major diastereomeric carbinols at 140 °C gave d- and /-menthone, respectively, in high enantiomeric purities (90-93% ee). This methodology has been successfully applied to the resolution of other 2-substituted cyclohexanones as well as other chiral ketones that have served as advanced synthetic intermediates for the synthesis of natural products.66-69... 

The geometry of the alkene is determined solely by the chirality at sulfur of the P-hydroxy sulfoximines 99 and 101 were converted to the (Z)- and ( )-vinyl sulfoximines 100 and 102, respectively, in high yield and with a high product diastereoselection (99 1). 

Resolved P-hydroxy sulfoximines derived from cyclic enones undergo dias-tereoselective Simmons-Smith cyclopropanation reactions to give, after thermolysis, cyclopropylketones in high enantiomeric purity (94-98%). Cyclopropanation occurs syn to the hydroxyl group of the P-hydroxy sulfoximine. This method is less diastereoselective for acyclic enones.73... 

Osmylation of diastereomerically pure P-hydroxy sulfoximines, derived from 2a and cyclic enones, with a catalytic amount of osmium tetroxide (5 mol%) and trimethylamine V-oxide (1.5 equiv) gives diastereomerically pure triols which on thermolysis yield 2,3-dihydroxy cyclic ketones in high enantiomeric purity ( 100% ee). Osmylation occurs syn to the sulfoximine group.74... 

For the use of optically active P-hydroxy sulfoximines as ligands for enantioselective catalytic reactions, see Section VII. 

P-Keto sulfoximines 300 undergo diastereoselective reductions at -78 °C with sodium borohydride or diborane to give mixtures of diastereomeric P-hydroxy sulfoximines. The product diastereoselection increases as the steric demand of the substituent R of 300 increases (Table 19). Reductive removal of the P-sulfoximine group of the diastereomeric mixture of P-hydroxy sulfoximines gives secondary alcohols with the (S)-configuration.125... 

The X-ray crystal structures of p-hydroxy sulfoximines coordinated to metals are known, including complexes to ethylzinc127 and vanadium.128 These complexes involve coordination of the metal to the hydroxyl oxygen and the sulfoximine nitrogen. A palladium(II) bidentate pyridine-sulfoximine complex129 and simple sulfoximine-copper(II) and zinc complexes are also known.130 These latter complexes involve coordination of the metal to the sulfoximine nitrogen. 

In 1979, Johnson reported the enantioselective reduction of ketones with stoichiometric amounts of optically active (1-hydroxy sulfoximine-borane complexes.131 Prochiral alkyl phenyl ketones (RCOPh) undergo enantioselective reduction with enantiomerically pure p-hydroxy sulfoximine borane complexes (301 and 302). These complexes are prepared by reaction of the corresponding P-hydroxy sulfoximine with borane at -78 °C. The structures 301 and 302 have been suggested for these complexes. In the case of the borane complex 301, the enantioselectivity increased as the steric bulk of the R substituent of the ketone (RCOPh) was decreased from IV to Me. The analogous reductions of methyl alkyl ketones (MeCOR) with these borane complexes were less enantioselective (3-27% ee).131... 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

Chiral titanium reagents derived from optically active P-hydroxy sulfoximines and Ti(0-Pri)4 promote the asymmetric addition of trimethylsilyl cyanide to aldehydes.137 The resulting cyanohydrins are generally formed in 74-91% enan-... 

Fu reported the enantioselective addition of diphenylzinc to ketones catalyzed by chiral amino alcohol 6, and observed a slight asymmetric amplification [13]. Bolm also reported asymmetric amplification in enantioselective alkylations using diethylzinc promoted 1 a chiral 2-pyridyl alkanol 7 and p-hydroxy sulfoximine 8 (Scheme 9.6) [14,15]. 

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