Sulfone Group as a Versatile and Removable Directing Group for Asymmetric Transfer Hydrogenation of Ketones

Abstract The sulfone functional group has a strong capacity to direct the asymmetric transfer hydrogenation (ATH) of ketones in the presence of [(arene)Ru(TsDPEN)H] complexes by adopting a position distal to the η6‐arene ring. This preference provides a means for the prediction of the sense of asymmetric reduction. The sulfone group also facilitates the formation of a range of reduction substrates, and its ready removal provides a route to enantiomerically enriched alcohols that would otherwise be extremely difficult to prepare by direct ATH of the corresponding ketones.

This compound was prepared in racemic form following procedure C using: 1-cyclopropyl-2-
This compound was prepared in enantiomerically-enriched form following procedure D, using

Racemic and (S)-1-phenoxypentan-2-ol
This compound is known and has been fully characterized.
This compound was prepared in enantiomerically-enriched form following procedure D, using

This compound is known and has been fully characterized
To a solution of methyl phenyl sulphone (1.09 g, 7.0 mmol, 1.0 equiv) in dry THF (30 mL) was added nBuLi (2.5 M in n-hexane, 3.10 mL, 7.70 mmol, 1.1 equiv) dropwise at -78 ºC under nitrogen atmosphere. After the reaction mixture had been stirred at -78 o C for 30 minutes, N-methoxy-N-methyl-2-phenylacetamide (1.40 g, 7.70 mmol, 1.1 equiv) was added dropwise at -78 o C. Upon stirring at same temperature for 1 h, the reaction mixture was stirred at ambient temperature for 1 h. It was then concentrated under reduced pressure, extracted with ethyl acetate (2 x 30 mL), washed with brine (50 mL), dried over Na2SO4, filtered,
This compound was prepared in racemic form following procedure C using: 1-phenyl-3-

S27
This compound is novel.
This compound was prepared in enantiomerically-enriched form following procedure D, using

Racemic and (S)-tert-butyl
This compound is novel.

Racemic and
This compound is novel.
This compound was prepared in enantiomerically-enriched form following procedure D, using

3037-3041
This compound was prepared following procedure F using: 1-phenoxy-3- This compound also made by using this procedure: To a solution of methyl phenyl sulphone (1.0 g, 6.41 mmol, 1.0 equiv) in dry THF (30 mL) was added nBuLi (2.5 M in n-hexane, 3
This compound was prepared in enantiomerically-enriched form following procedure D, using
This compound was prepared following procedure F using: 1-phenoxy-4-
This compound was prepared following procedure F using: 1-phenoxy-3-

S51
This compound is known and has been fully characterized.
This compound was prepared following procedure G using: (1S,2S)-1-methoxy-3-phenoxy-1- This compound was prepared in racemic form following this procedure: To methanol (20 mL), sodium hydride (400 mg, 10 mmol, 1.5 eq) was added and the mixture was stirred at room temperature for 30 minutes to allow deprotonation. Phenyl glycidyl ether (1.0 g, 6.7 mmol, 1 eq) was then added and allowed to react for at least 2 hours at room temperature. The reaction was quenched with ammonium chloride (10 mL). Ethyl acetate (20 mL) and water (10 mL) were added to allow clear separation into two layers. The organic layer was extracted using ethyl acetate (3 x 10 mL) and water (10 mL) and was dried using sodium sulfate, filtered and concentrated in vacuo to give the 1-methoxy-3-phenoxypropan-2-ol as a colourless oil (946 mg, 5.19 mmol, 77.9%).  For control experiment, this compound was already been reported via ATH in the following reference and was reduced in 7% ee.
This compound was prepared in racemic form following procedure D using: 1-
This compound was prepared using following this procedure:-To a stirred solution of (S)-1- This compound is known and has been fully characterized. The crystal of obtained adduct was grown from DCM/Hexane. Solid state structure of one of the crystalographically independent but chemically identical molecules in the asymmetric unit of vv1 with atom labelling and thermal ellipsoids drawn at 50% probability level

Crystal structure determination of [vv1_twin1_hklf5]
The asymmetric unit contains two crystallographically independent but chemically identical molecules in the asymmetric unit, twice this in the unit cell. The molecule has crystalised in a chiral space group and after the twin refinement, the Flack parameter is smallish with a small error. As there is already a chiral center of known handedness in the molecule from the methylbenzyl carbamate the Flack is not essential for confirming the absolute configuration. The crystal was kept at 150(2) K during data collection.
The harvesting of the spots and integration was performed with the twin module in the CrysAlisPro software package [1]. Using Olex2 [2], the structure was solved using the reflections from the maJor twin component with ShelXT [3] structure solution program using Intrinsic Phasing and the reflection data for the two components refined in the hklf5 format with the ShelXL [4] refinement package using Least Squares minimization S219 (5.814° ≤ 2Θ ≤ 148.212°), 15332 unique (Rint = ?(no meaningful number for this as twinned data), Rsigma = 0.0667) which were used in all calculations. The final R1 was 0.0419 (I > 2σ(I)) and wR2 was 0.1181 (all data). Table 1 Crystal data and structure refinement for vv1_twin1_hklf5 ( Figure 5B).

Identification code vv1_twin1_hklf5
Empirical formula C23H29NO4S