Asymmetric α-Sulfonyl- and α-Phosphoryl-Oxylation of Ketones by a Chiral Hypervalent Iodine(III)

Article abstract of DOI:10.1021/acs.joc.7b01597

An enantioselective direct oxygenation of propiophenone derivatives mediated by a catalytic or stoichiometric amount of new chiral non-C2-symmetric iodoarenes(III) is reported. The reaction gives an easy entry to optically active α-sulfonyl- and α-phosphoryl oxyketones in respectable yields and enantioselectivities.

Full text of DOI:10.1021/acs.joc.7b01597

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Note
Asymmetric #-Sulfonyl- and #-Phosphoryl-oxylation
of Ketones by a Chiral Hypervalent Iodine(III)
Guillaume Levitre, Audrey Dumoulin, Pascal Retailleau,
Armen Panossian, Frederic R. Leroux, and Géraldine Masson
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01597 • Publication Date (Web): 21 Jul 2017
Downloaded from http://pubs.acs.org on July 21, 2017
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The Journal of Organic Chemistry
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Asymmetric αꢀSulfonylꢀ and αꢀPhosphorylꢀoxylation of
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Ketones by a Chiral Hypervalent Iodine(III)
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Guillaume Levitre, † Audrey Dumoulin, † Pascal Retailleau, † Armen Panossian, ‡ Frédéric R.
Leroux, ‡ Géraldine Masson†*
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†
Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université ParisꢀSud, Université
ParisꢀSaclay, 1, av. de la Terrasse, 91198 GifꢀsurꢀYvette Cedex, France.
‡ Université de Strasbourg, CNRS, LCM UMR 7509, 67000 Strasbourg, France
AUTHOR EMAIL ADDRESS: geraldine.masson@cnrs.fr
ABSTRACT
An enantioselective direct oxygenation of propiophenone derivatives mediated by a catalytic or
stoichiometric amount of new chiral nonꢀC2ꢀsymmetric iodoarenes(III) is reported. The reaction gives
an easy entry to optically active αꢀsulfonylꢀ and αꢀphosphoryl oxyketones in respectable yields and
enantioselectivities.
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Enantiomerically enriched αꢀoxygenated ketones are valuables motifs frequently encountered in
natural products and pharmaceuticals, and are versatile synthetic intermediates in organic synthesis.1
Accordingly, substantial work has been dedicated to the development of catalytic enantioselective
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methods for their synthesis.2 Recently, αꢀoxygenation of ketones mediated by chiral hypervalent
iodine(III) reagents (λ3ꢀiodanes) has received extensive attention,3ꢀ5 however, the various possible
mechanistic pathways made the development of asymmetric versions particularly challenging and only
few efficient chiral λ3ꢀiodanes have been reported to date.6 Wirth et al. disclosed the first example of
enantioselective αꢀtosyloxylation of propiophenone using a stoichiometric amount of chiral
hydroxy(tosyloxy)iodo]benzene derivatives 1a (Figure 1, up to 15% ee).7 Subsequently, the same group
developed catalytic variants using mꢀchloroperbenzoic acid (mꢀCPBA) as a coꢀoxidant with chiral
iodane 1b and up to 39% ee was obtained.8 Later on, Zhang et al. reported that spirobiindaneꢀbased
chiral iodoarenes 1c catalyzed the formation αꢀtosyloxylated ketones in moderate yield and with up to
52% ee.9 In 2012, Moran et al. used various chiral aryl iodides containing norephedrine moieties 1d in
the sulfonyloxylation reaction; however, only moderate enantioselectivities were achieved (up to 18%
ee).10 In the same year, Legault et al. accomplished an enantioselective tosyloxylation of ketones using a
designed iodoaryloxazoline catalyst 1e with enantioselectivities of up to 54% ee.11 Shortly after,
Berthiol et al. introduced a new 3,3'ꢀdiiodoꢀBINOLꢀfused maleimide derivative 1f that showed a
comparable stereochemical efficiency to the best results reported to date (up to 50% ee).12 More
recently, great progress has been achieved by Legault et al., who documented a highly enantioselective
tosyloxylation of enol esters (up to 90% ee) using a stoichiometric quantity of a chiral flexible C2ꢀ
symmetric iodoarene 1g.13 However, in spite of this significant progress, the requirement of preformed
enols and excess amount of chiral iodanes(III) might hamper the synthetic application of this protocol.
Thus, it is still worth to develop a catalytic enantioselective efficient αꢀtosyloxylation of ketones. As a
part of our continuous interest towards using the newly developed family of chiral C2ꢀsymmetric and
nonꢀC2ꢀsymmetric iodoarene precatalysts,14 we have recently realized a catalytic enantioselective
oxidative spirolactonization of 1ꢀnaphthol.14a We speculated that these chiral hypervalent iodine
precursors may catalyze an efficient enantioselective αꢀoxygenation of ketones.
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OTs
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I
O
HO
I
R
I
Ph
OH
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H
Et
1a R = OMe or OBn
1b R = CO2( )-Menthyl
1c
1d
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Ph
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OR
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NAr
O
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O
1g R =
N
1f
1e
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Ph
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Figure 1. Chiral catalysts for the αꢀsulfonyloxylation of ketones
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To test our hypothesis, we examined the reaction of propiophenone (2a) with 3 equiv of mꢀCPBA and
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3 equiv of pꢀTsOH•H2O 4a in the presence of a chiral C2ꢀsymmetric iodoarenes(III) 1h and 1i (10
mol%) in Et2O at rt. While desired αꢀtosyloxy ketone 3a was isolated in 35% and 41% yield with 1h
and 1i, only ꢀ6 and ꢀ11% ee, respectively, were obtained (Table 1, entries 1 and 2). Interestingly, nonꢀ
C2ꢀsymmetric iodoarene precatalyst incorporating an acetamide group 1j gave better enantioselectivity
(ꢀ25% ee). Encouraged by this result, a series of nonꢀC2ꢀsymmetric iodoarenes (> 98% ee) were
synthesized15 and screened as precatalysts in this reaction. As summarized in table 1, the precatalyst
with an enantioenriched (R)ꢀtertꢀbutyl sulfoxide (1k)16 gave much better results in terms of ee (entries 4
vs 3). On the other hand, when the chiral precursor 1l had a methoxy group at R4, the enantioselectivity
was noticeably lower (entry 5). Then, we envisioned that the sulfoxide could be partially or totally
oxidized under these conditions. Indeed, when the sulfone derivative precatalyst 1m was used, a similar
result was obtained, indicating that sulfone 1m is the active precatalyst. After that we were pleased that
the amount of mꢀCPBA and pꢀTsOH•H2O could be reduced to 2 equivalents without decreasing
efficiency. Solvent effect was next examined and EtOAc was found to be the best reaction medium. In
this solvent, the desired product 3a was isolated in 75% yield with 67% ee (entry 11). Unfortunately,
lowering the reaction temperature reduced significantly the yield of 3a without positive impact on
enantioselectivity (entry 14). Next, various oxidants were screened (entries 12 and 13), and mꢀCPBA
was found to be the most efficient oxidant for this reaction. The absolute configuration of 3a with 1kꢀm
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as catalyst was determined to be (R) by comparison of the sign of its optical rotation with that of the
literature data.8 Finally, to show the versatility of this reaction, we performed the oxytosylation using 1n
(opposite enantiomer of 1m, prepared at 95% ee) as the catalyst. As expected, the antipode of 3a was
formed in almost similar yield and the same enantioselectivity (entry 15).
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Table 1. Reaction Parameters.a
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Entry
1
oxidant
Solvent
Et2O
x
3
3a yield (%)b 3a ee (%)c
1
mꢀCPBA
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88
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<10
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67
ꢀ6d
ꢀ11d
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65e
32e
62e
65e
23e
25e
25e
67e
25e,f
7e
1h
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3
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
mꢀCPBA
Oxone®
Et2O
Et2O
3
3
3
3
3
2
2
2
2
2
2
2
2
2
1i
1j
4
Et2O
1k
5
Et2O
1l
6
Et2O
1m
1m
1m
1m
1m
1m
1m
1m
1m
1n
7
Et2O
8
CH3CN
CH3NO2
HFIP
EtOAc
HFIP
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H2O2/H2O EtOAc
mꢀCPBA
mꢀCPBA
EtOAc
EtOAc
65 e,g
ꢀ63d
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a General conditions: 2a (0.10 mmol), 4 (x eq), 1 (0.01 mmol) and mꢀCPBA (x eq) in 1.0 mL of solvent. b Yields referred to
c d e
chromatographically pure product. Determined by HPLC analysis on chiral stationary phases. (S)ꢀenrichedꢀ3b. (R)ꢀ
enrichedꢀ3a. f Traces of product are observed if the reaction is carried out in ethyl acetate. g Reaction performed at 0 °C.
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Under the optimal conditions established, the scope of this asymmetric αꢀsulfonyloxylation of ketones
was then explored. As shown in Scheme 1, the reaction of a range of aromatic ketones bearing various
substituents was investigated first. The electronic properties of the substituents on the phenyl ring did
not affect too much the enantioselectivity, but did impact the yield. For instance, ketones bearing
electronꢀwithdrawing substituents such as F or CF3 gave the desired products 3c and 3d in good yields,
while strong electronꢀdonating substituent such as MeO (3f) and Me (3g) groups led to decreased yields.
Pleasingly, when the reaction was carried out with 20 mol% of 1m, 3f and 3g were isolated in better
yield. The presence of metaꢀsubstituents such as CF3 or Cl was well tolerated (3d and 3e). A sterically
more demanding 1ꢀnaphthyl group was also compatible affording the oxytosylated product 3j in 69%
yield with 61% ee. A ketone with a heteroaromatic group such as thiophene showed a deleterious effect
on yield, although good enantioselectivity was retained (3h). However, in the presence of 20 mol% of
1m, the resulting oxytosylatedꢀketone 3h was isolated in slightly better yield (38%). With regard to the
nature of the substituent R2, the ethyl group provided the desired product 3i, although in somewhat
lower yield and enantioselectivity. Extension of this oxylation protocol to other sulfonyl acid groups
was delightfully successful. For instance, 1ꢀnaphthalenesulfonic acid provided the corresponding αꢀ
tosyloxylated ketones 3kꢀm, respectively in similar yields and enantioselectivities. Interestingly, split
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peaks were observed in the H, and C NMR spectra as well as HPLC analysis of products 3kꢀm,
resulting from the atropisomerism arising from the hindered rotation along the C−S bond. In addition,
the methanesulfonic acid furnished the corresponding products 3n with lower yield but the
enantioselectivity was maintained at 62% ee. Fortunately, the use of 20 mol% 1m was successful
leading to 3n in respectable yield. After successfully synthesizing enantioenriched αꢀsulfonyloxyꢀ
ketones, we attempted to further evaluate the reaction scope using diphenylphosphate (4d) as an
oxygenꢀcontaining nucleophile under the same conditions (Scheme 1).17 Disappointingly, the desired αꢀ
phosphoryloxyꢀketone 3o was obtained in low yield (23%) albeit with 62% ee. Pleasingly, the
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stoichiometric addition of the chiral iodane precursor 1m ensured a higher yield of 3o (63%) without
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Scheme 1. Substrate scope of the enantioselective αꢀoxygenation of propiophenone derivatives 2.a,b,c
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a General conditions: 2a (0.10 mmol), 2 (2 eq), 1m (0.01 mmol) and mꢀCPBA (0.20 mmol) in 1.0 mL of solvent. Yields
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referred to chromatographically pure product. Determined by HPLC analysis on chiral stationary phases. Reaction
performed with 1m (0.02 mmol). e Reaction performed with 1m (0.10 mmol).
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affecting the enantioselectivity. To the best of our knowledge, this method represents the first αꢀ
phosphoryloxylation of ketones.17 A set of propiophenone derivatives with diverse substituents, such as
methyl and fluoro groups, were well tolerated in this enantioselective oxidative reaction (3q and 3r).
For instance, 1ꢀphenylbutanone 2h and 1ꢀ(naphthalenꢀ2ꢀyl)propanone 2i also afforded the
corresponding products 3s and 3p, respectively with moderate yield and enantioselectivity.
A plausible mechanism is proposed in scheme 2 on the basis of earlier mechanistic studies.3,7,8 First,
the enol form of propiophenone may react with the arylꢀλ3ꢀiodane 5 generated in situ from reaction of
the chiral iodoarene 1, mꢀCPBA and sulfonic acid or diphenyl phosphate 4, to provide a C−IꢀAr* bond
6. Subsequent nucleophilic addition of oxygenated nucleophile upon the C−IꢀAr* 6 would lead to 3,
meanwhile the reductive elimination of λ3ꢀiodane would occur to release the chiral iodoarene 1.
Alternatively, the reaction can proceed through the Oꢀenolate (O−I−Ar*) intermediate 7, on the basis of
computational results reported by Legault.6 According to this study, the transꢀenolate intermediate 7
may react with oxygenated nucleophile via a nucleophilic substitution of type SN2’ 8 to form 3 along
with regeneration of iodoarene precatalyst.
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Scheme 2. Activation model via a putative transition state.
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In conclusion, new chiral nonꢀC2ꢀsymmetric iodoarenes(III) were found to be effective catalysts for
the asymmetric αꢀsulfonylꢀ and phosphorylꢀoxylation of ketones. This method delivers valuable αꢀ
oxygenated ketones with respectable yields and enantioselectivities.
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EXPERIMENTAL SECTION
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Materials and General methods. All reactions were carried out under argon atmosphere in oven
dried glassware with magnetic stirring. Reagents were obtained from commercial supplier and used
without further purification unless otherwise noted. All solvents used in the reactions were distilled
from appropriate drying agents prior to use. Analytical thin layer chromatography (TLC) was purchased
from Merck KGaA (silica gel 60 F254). Visualization was accomplished by irradiation with a UV light
at 254 nm. Flash column chromatography was carried out using kieselgel 35ꢀ70 ꢁm particle sized silica
gel (200ꢀ400 mesh). Chromatography was performed using silica gel 60 (0.040ꢀ0.063 mm) from Merck.
Proton chemical shifts are reported in ppm (δ) relative to tetramethylsilane (TMS) with the solvent
resonance employed as the internal standard (CDCl3, δ 7.26 ppm). Data are reported as follows:
chemical shift, multiplicity (s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, qt =
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quintuplet, h = hexuplet, ht = heptuplet, m = multiplet), coupling constants (Hz) and integration. C
chemical shifts are reported in ppm from tetramethylsilane (TMS) with the solvent resonance as the
internal standard (CDCl3, δ 77.0 ppm). The characteristic IR absorption frequencies are reported in cmꢀ1.
Highꢀresolution mass spectra (HRMS) were determined on an AEI MSꢀ9 using electrospray ionization
(ESI) and a timeꢀofꢀflight (TOF) analyzer. Enantiomeric excesses were determined by high performance
liquid chromatography (HPLC) equipped with diode array UV detectors, using Chiralpak IA and ODꢀH
columns. Chiral iodoarenes were synthesized according to reported literature procedures.15
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Preparation of Catalyst (R)ꢀ2ꢀ(tertꢀbutylsulfonyl)ꢀ6ꢀchloroꢀ2'ꢀiodoꢀ1,1'ꢀbiphenyl (1m). Reaction on
419 mg of 1k15(b) (1.0 mmol, 1 equiv) in CHCl3 (10 mL) at 0 °C, was added mꢀCPBA (2 mmol, 213mg,
2 equiv). The reaction mixture was stirred at 0 °C for 4 h (monitoring by TLC). After completion of the
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reaction, a fresh aqueous solution of Na2S2O3 was added followed by an aqueous solution of NaHCO3.
The aqueous and organic layers were separated and the aqueous layer was extracted with EtOAc. The
combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The crude was
purified by flash chromatography on silica gel (Heptane/EtOAc 7/3) to afford 425 mg of white solid,
98% yield. Some recrystallization (Hexane/AcOEt) of products can increase the enantiomeric excess up
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to 98%. [α]22D +33.0 (c 0.1, CHCl3); Mp: decomposition observed at 140ꢀ145°C; H NMR (300 MHz,
7
CDCl3) δ (ppm) 8.00 (dd, J = 7.8 Hz and J = 1.2 Hz, 1 H), 7.92 (dd, J = 7.8 Hz and J = 1.2 Hz, 1 H),
7.80 (dd, J = 7.8 Hz and J = 1.2 Hz, 1 H), 7.55 (t, J = 7.8 Hz, 1 H), 7.41 (td, J = 7.5 Hz and J = 1.2 Hz,
1 H), 7.19 (dd, J = 7.5 Hz and J = 1.2 Hz, 1 H), 7.11 (td, J = 7.8 and J = 1.8 Hz, 1 H), 1.29 (s, 9H).;
13C NMR (75 MHz, CDCl3) δ (ppm) 143.8, 141.3, 138.6, 137.2, 136.3, 135.0, 131.9, 130.0, 129.7,
129.1, 127.1, 101.9, 61.8, 24.2. Enantiomeric excess is 98% determined by HPLC (Chiralpak ODꢀH,
Hexane/EtOH = 99/1, flow rate = 1.0 mL/min, 214 nm): major isomer: tR = 17.5 min, minor isomer: tR =
15.8 min. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H17ClIO2S 434.9702; found 434.9714.
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Preparation of Catalyst (S)ꢀ2ꢀ(tertꢀbutylsulfonyl)ꢀ6ꢀchloroꢀ2'ꢀiodoꢀ1,1'ꢀbiphenyl (1n). Reaction
on 419 mg of 1k’15(b) (1.0 mmol, 1 equiv) in CHCl3 (10 mL) at 0 °C, was added mꢀCPBA (2 mmol, 213
mg, 2 equiv). The reaction mixture was stirred at 0 °C for 4 h (monitoring by TLC). After completion of
the reaction, a fresh aqueous solution of Na2S2O3 was added followed by an aqueous solution of
NaHCO3. The aqueous and organic layers were separated and the aqueous layer was extracted with
EtOAc. The combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The
crude was purified by flash chromatography on silica gel (Heptane/EtOAc 7/3) to afford 425 mg of
white solid, 98% yield. Some recrystallization (Hexane/AcOEt) of products can increase the
enantiomeric excess up to 95%. [α]22 -28.0 (c 0.1, CHCl3); Mp: decomposition observed at 140ꢀ
D
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145°C; H NMR (300 MHz, CDCl3) δ (ppm) 8.00 (dd, J = 7.8 Hz and J = 1.2 Hz, 1 H), 7.92 (dd,
J = 7.8 Hz and J = 1.2 Hz, 1 H), 7.80 (dd, J = 7.8 Hz and J = 1.2 Hz, 1 H), 7.55 (t, J = 7.8 Hz, 1 H), 7.41
(td, J = 7.5 Hz and J = 1.2 Hz, 1 H), 7.19 (dd, J = 7.5 Hz and J = 1.2 Hz, 1 H), 7.11 (td, J = 7.8 and
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J = 1.8 Hz, 1 H), 1.29 (s, 9H).; C NMR (75 MHz, CDCl3) δ (ppm) 143.9, 141.3, 138.6, 137.2, 136.5,
135.1, 131.9, 130.0, 129.7, 129.1, 127.2, 101.9, 61.9, 24.3.; Enantiomeric excess is 95% determined by
HPLC (Chiralpak ODꢀH, Hexane/EtOH = 99/1, flow rate = 1.0 mL/min, 214 nm): major isomer: tR =
15.6 min, minor isomer: tR = 17.6 min. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H17ClIO2S
434.9702; found 434.9714.
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Typical Procedure for Asymmetric αꢀSulfonyloxylation A: In a test tube, sulfonic acid (0.2 mmol,
2.0 equiv), carbonyl compound 2 (0.1 mmol, 1.0 equiv) and the catalyst 1m (4.3 mg, 0.01 mmol, 0.1
equiv) were dissolved in EtOAc (1.0 mL) at room temperature. Then, mꢀCPBA (44.8 mg, 0.2 mmol, 2.0
equiv, ≤ 77%) was added and the reaction mixture was stirred for 72 hours. The resulting solution was
quenched with a saturated aqueous Na2S2O3 solution (1 mL) and a saturated aqueous Na2CO3 solution
(1 mL). The aqueous layer was extracted with EtOAc (3 x 5 mL), the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The
residue was purified over preparative TLC plate using (Heptane/EtOAc 7/3) as an eluent to give the
desired product 3.
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Typical Procedure for Asymmetric αꢀSulfonyloxylation B: In a test tube, sulfonic acid (0.2 mmol,
2.0 equiv), carbonyl compound 2 (0.1 mmol, 1.0 equiv) and the catalyst 1m (8.6 mg, 0.02 mmol, 0.2
equiv) were dissolved in EtOAc (1.0 mL) at room temperature. Then, mꢀCPBA (44.8 mg, 0.2 mmol, 2.0
equiv, ≤ 77%) was added and the reaction mixture was stirred for 72 hours. The resulting solution was
quenched with a saturated aqueous Na2S2O3 solution (1 mL) and a saturated aqueous Na2CO3 solution
(1 mL). The aqueous layer was extracted with EtOAc (3 x 5 mL), the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The
residue was purified over preparative TLC plate using (Heptane/EtOAc 7/3) as an eluent to give the
desired product 3.
Typical Procedure for Asymmetric αꢀPhosphoryloxylation C: In a test tube, diphenylphosphate
(0.2 mmol, 2.0 equiv), carbonyl compound 2 (0.1 mmol, 1.0 equiv) and the catalyst 1m (43.0 mg, 0.1
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mmol, 1 equiv) were dissolved in EtOAc (1.0 mL) at room temperature. Then, mꢀCPBA (44.8 mg, 0.2
mmol, 2.0 equiv, ≤ 77%) was added and the reaction mixture was stirred for 72 hours. The resulting
solution was quenched with a saturated aqueous Na2S2O3 solution (1 mL) and a saturated aqueous
Na2CO3 solution (1 mL). The aqueous layer was extracted with EtOAc (3 x 5 mL), the combined
organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under
reduced pressure. The residue was purified over preparative TLC plate using (Heptane/EtOAc 7/3) as an
eluent to give the desired product 3.
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(2R)ꢀ2ꢀ[(4ꢀmethylbenzenesulfonyl)oxy]ꢀ1ꢀphenylpropanꢀ1ꢀone (3a).9 Prepared according to the
general procedure A. Reaction on 13.4 mg (0.10 mmol) of propiophenone (2a). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford 22.7 mg of a colorless oil, 75% yield. [α]22D –5.5 (c 1.0,
CHCl3); IR 3065, 2926, 1698, 1359, 1190, 918 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.88 (d, J =
7.3 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.60 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.28 (d, J = 8.2
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Hz, 2H), 5.79 (q, J = 6.9 Hz, 1H), 2.42 (s, 3H), 1.60 (d, J = 6.9 Hz, 3H). C NMR (75 MHz, CDCl3)
δ (ppm) 195.0, 145.1, 133.9, 133.8, 133.6, 129.9, 128.9, 128.1, 77.4, 21.8, 18.9.; Enantiomeric excess is
67% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm):
major isomer: tR = 10.9 min, minor isomer: tR = 12.2 min.
(2S)ꢀ2ꢀ[(4ꢀmethylbenzenesulfonyl)oxy]ꢀ1ꢀphenylpropanꢀ1ꢀone (3b).9 Prepared according to the
general procedure A. Reaction on 13.4 mg (0.10 mmol) of propiophenone (2a). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford 20.3 mg of a colorless oil, 67% yield. [α]22D +5.2 (c 1.0,
CHCl3); IR 3065, 2926, 1698, 1359, 1190, 918 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.88 (d, J =
7.6 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H), 7.59 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.26 (d, J = 7.9
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Hz, 2H), 5.78 (q, J = 6.9 Hz, 1H), 2.41 (s, 3H), 1.60 (d, J = 6.9 Hz, 3H). C NMR (75 MHz, CDCl3)
δ (ppm) 195.0, 145.1, 133.9, 133.8, 133.6, 129.9, 128.9, 128.1, 77.4, 21.8, 18.9.; Enantiomeric excess is
63% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm):
major isomer: tR = 12.4 min, minor isomer: tR = 11.0 min.
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(R)ꢀ1ꢀ(4ꢀFluorophenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3c).11a Prepared according
to the general procedure A. Reaction on 15.2 mg (0.10 mmol) of 4’ꢀfluoropropiophenone (2b). Eluent
for the preparative TLC: heptane/MTBE 7/3, to afford 22.6 mg of a colorless oil, 70% yield. [α]22D +5.1
(c 1.0, CHCl3); IR 2991, 1702, 1598, 1508, 1362, 1229, 1191, 1177, 1161, 1017, 922, 817, 666 cmꢀ1;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.94 (dd, J = 8.1, 5.7 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.28 (d, J
= 8.8 Hz, 2H), 7.13 (t, J = 8.5 Hz, 2H), 5.70 (q, J = 6.9 Hz, 1H), 2.42 (s, 3H), 1.58 (d, J = 6.9 Hz, 3H).;
Enantiomeric excess is 64% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate =
1.0 mL/min, 254 nm): major isomer: tR = 11.2 min, minor isomer: tR = 13.3 min.
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(R)ꢀ1ꢀ(3ꢀ(Trifluoromethyl)phenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl
4ꢀmethylbenzenesulfonate
(3d).11a
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Prepared according to the general procedure A. Reaction on 20.2 mg (0.10 mmol) of
3’ꢀtrifluoromethylpropiophenone (2d). Eluent for the preparative TLC: heptane/MTBE 7/3, to afford
24.5 mg of a colorless oil, 66% yield. [α]20 +3.0 (c 1.0, CHCl3); IR 2925, 1704, 1363, 1331, 1191,
D
1
1174, 1129, 1073, 924, 816, 665 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 8.09 (d, J = 7.8 Hz, 2H),
7.82 (d, J = 7.7 Hz, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.31 – 7.19 (m, 2H), 5.69 (q,
J = 6.9 Hz, 1H), 2.39 (s, 3H), 1.61 (d, J = 6.9 Hz, 3H).; Enantiomeric excess is 64% determined by
HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 8.1
min, minor isomer: tR = 9.2 min.
(R)ꢀ1ꢀ(3ꢀchlorophenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3e). Prepared according to
the general procedure A. Reaction on 16.9 mg (0.10 mmol) of 3’ꢀchloropropiophenone (2e). Eluent for
the preparative TLC: heptane/MTBE 7/3, to afford, 20.5 mg of colorless oil, 61% yield. [α]22 +8.9 (c
D
1.0, CHCl3); IR 3069, 2926, 1705, 1364, 1222, 1191, 1177, 1018, 927, 925, 815, 784, 734, 666 cmꢀ1;
1H NMR (300 MHz, CDCl3) δ (ppm) 7.84 – 7.67 (m, 4H), 7.55 (d, J = 8.2 Hz, 1H), 7.40 (t, J = 7.8 Hz,
1H), 7.27 (d, J = 7.8 Hz, 2H), 5.68 (q, J = 6.9 Hz, 1H), 2.42 (s, 3H), 1.59 (d, J = 6.9 Hz, 3H). 13C NMR
(75 MHz, CDCl3) δ (ppm) 194.1, 145.4, 135.4, 135.3, 133.8, 133.4, 130.2, 130.0, 128.9, 128.1, 127.0,
77.6, 21.8, 18.7.; Enantiomeric excess is 61% determined by HPLC (Chiralpak IA, Heptane/iPrOH =
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90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 11.6 min, minor isomer: tR = 15.0 min.
HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C16H16ClO4S 339.0459; found 339.0446.
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(R)ꢀ1ꢀ(4ꢀmethoxyphenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3f).9 Prepared according
to the general procedure B. Reaction on 16.4 mg (0.10 mmol) of 4’ꢀmethoxypropiophenone (2f). Eluent
for the preparative TLC: heptane/MTBE 7/3, to afford 21.0 mg of a colorless oil, 62% yield. [α]20D +1.0
(c 1.0, CHCl3); IR 2926, 1696, 1599, 1263, 1177, 921, 748 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm)
7.87 (d, J = 8.9 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.9 Hz, 2H),
5.72 (q, J = 6.9 Hz, 1H), 3.86 (s, 3H), 2.39 (s, 3H), 1.56 (d, J = 6.9 Hz, 3H).; Enantiomeric excess is
61% determined by HPLC (Chiralpak ODꢀH, Hexane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm):
major isomer: tR = 13.5 min, minor isomer: tR = 15.4 min.
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(R)ꢀ1ꢀ(4ꢀmethylphenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3g).11a Prepared according
to the general procedure B. Reaction on 14.8 mg (0.10 mmol) of 4’ꢀmethylpropiophenone (2g). Eluent
for the preparative TLC: heptane/MTBE 7/3, to afford 20.3 mg of a colorless oil, 64% yield. [α]20D +5.1
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(c 1.0, CHCl3); IR 2923, 1697, 1607, 1362, 1190, 1176, 922, 816, 665 cmꢀ1; H NMR (300 MHz,
CDCl3) δ (ppm) 7.82 – 7.72 (m, 4H), 7.30 – 7.22 (m, 4H), 5.77 (q, J = 6.9 Hz, 1H), 2.41 (s, 6H), 1.58
(d, J = 6.9 Hz, 3H).; Enantiomeric excess is 65% determined by HPLC (Chiralpak IA, Heptane/iPrOH =
90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 11.9 min, minor isomer: tR = 14.3 min.
(R)ꢀ1ꢀoxoꢀ1ꢀ(thiophenꢀ2ꢀyl)propanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3h).9 Prepared according to
the general procedure B. Reaction on 14.0 mg (0.10 mmol) of 1ꢀ(thiophenꢀ2ꢀyl)propanꢀ1ꢀone (2h).
Eluent for the preparative TLC: heptane/MTBE 7/3, to afford, 15.8 mg of colorless oil, 38% yield. The
yield can be improved to 38% with 20mol% of the catalyst. [α]20D ꢀ2.0 (c 0.1, CHCl3); IR 2925, 1673,
1413, 1358, 1191, 1177, 1017, 945, 891, 852, 816, 736, 666 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm)
7.88 (d, J = 3.8 Hz, 1H), 7.76 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 4.8 Hz, 1H), 7.27 (d, J = 9.1 Hz, 2H),
7.19 – 7.11 (m, 1H), 5.45 (q, J = 6.9 Hz, 1H), 2.41 (s, 3H), 1.59 (d, J = 6.9 Hz, 3H).; Enantiomeric
excess is 68% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min,
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254 nm): major isomer: tR = 12.2 min, minor isomer: tR = 13.3 min.
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(R)ꢀ2ꢀ[(4ꢀmethylbenzenesulfonyl)oxy]ꢀ1ꢀphenylbutanꢀ1ꢀone (3i).9 Prepared according to the
general procedure A. Reaction on 14.8 mg (0.10 mmol) of 1ꢀphenylbutanꢀ1ꢀone (2i). Eluent for the
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preparative TLC: heptane/MTBE 7/3, to afford 15.9 mg of colorless oil, 50% yield. [α]20 +6.0 (c 1.0,
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CHCl3); IR 2977, 1701, 1598, 1364, 1190, 1176, 952, 907, 862, 699 cmꢀ1; 1H NMR (300 MHz, CDCl3)
δ (ppm) 7.85 (d, J = 7.4 Hz, 1H), 7.74 (d, J = 8.3 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.45 (t, J = 7.6 Hz,
1H), 7.25 (d, J = 8.2 Hz, 1H), 5.56 (dd, J = 7.6, 5.2 Hz, 1H), 2.40 (s, 1H), 2.06 ꢀ1.86 (m, 1H), 0.98 (t, J
= 7.4 Hz, 1H).; Enantiomeric excess is 58% determined by HPLC (Chiralpak IA, Heptane/iPrOH =
90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 8.9 min, minor isomer: tR = 11.3 min.
(R)ꢀ1ꢀ(naphthalenꢀ2ꢀyl)ꢀ1ꢀoxopropanꢀ2ꢀyl 4ꢀmethylbenzenesulfonate (3j).9 Prepared according to
the general procedure A. Reaction on 18.4 mg (0.10 mmol) of 1ꢀ(naphthalenꢀ2ꢀyl)propanꢀ1ꢀone (2j).
Eluent for the preparative TLC: heptane/MTBE 7/3, to afford, 24.5 mg of colorless oil, 69% yield.
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[α]20 ꢀ2.2 (c 1.0, CHCl3); IR 2989, 1695, 1627, 1597, 1362, 1306, 1190, 1177, 1018, 945, 920, 817,
D
759, 666 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.40 (s, 1H), 7.90 (dd, J = 20.3, 8.1 Hz, 4H), 7.75
(d, J = 7.8 Hz, 2H), 7.67 – 7.53 (m, 2H), 7.20 (d, J = 7.8 Hz, 2H), 5.94 (q, J = 6.8 Hz, 1H), 2.35 (s, 3H),
1.67 (d, J = 6.8 Hz, 3H).; Enantiomeric excess is 61% determined by HPLC (Chiralpak IA,
Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 13.8 min, minor isomer:
tR = 16.2 min.
(R)ꢀ 1ꢀoxoꢀ1ꢀphenylpropanꢀ2ꢀyl naphthaleneꢀ1ꢀsulfonate (3k).9 Prepared according to the general
procedure A. Reaction on 13.4 mg (0.10 mmol) of propiophenone (2a). Eluent for the preparative TLC:
heptane/MTBE 7/3, to afford, 22.0 mg of colorless oil, 65% yield with two inseparable diastereoisomers
(90/10). [α]20 ꢀ1.8 (c 1.0, CHCl3); IR 3065, 2989, 1701, 1596, 1508, 1450, 1362, 1226, 1204, 1178,
D
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1127, 1015, 980, 970, 919, 804, 771, 702, 667 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 8.61 (d, J =
8.4 Hz, 1H), 8.25 (d, J = 7.3 Hz, 1H), 8.09 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 8.2 Hz, 1H), 7.79 (d, J = 7.4
Hz, 2H), 7.71 – 7.46 (m, 4H), 7.37 (t, J = 7.7 Hz, 2H), 5.85 (q, J = 6.9 Hz, 0.1H), 5.75 (q, J = 6.9 Hz,
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1H), 1.62 (d, J = 6.9 Hz, 0.3H), 1.53 (d, J = 6.9 Hz, 3H).; Enantiomeric excess is 64% determined by
HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major rotamer: major
isomer: tR = 11.0 min, minor isomer: tR = 12.2 min. minor rotamer: major isomer: tR = 14.8 min, minor
isomer: tR = 15.7 min..
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(R)ꢀ 1ꢀoxoꢀ1ꢀ(pꢀtolyl)propanꢀ2ꢀyl naphthaleneꢀ1ꢀsulfonate (3l). Prepared according to the general
procedure A. Reaction on 14.8 mg (0.10 mmol) of 4'ꢀmethylpropiophenone (2g). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford, 22.2 mg of colorless oil, 63% yield with two
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inseparable diastereoisomers (85/15). [α]22 ꢀ2.9 (c 1.0, CHCl3); IR 2920, 1697, 1607, 1508, 1362,
D
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1205, 1179, 1073, 1016, 980, 921, 834, 803, 771, 751, 678 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm)
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8.61 (d, J = 8.4 Hz, 1H), 8.24 (d, J = 7.3 Hz, 1H), 8.08 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 7.5 Hz, 1H),
7.68 (d, J = 8.3 Hz, 2H), 7.61 (dd, J = 9.7, 7.9 Hz, 2H), 7.51 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 8.0 Hz,
2H), 5.83 (q, J = 7.0 Hz, 0.15H), 5.73 (q, J = 6.9 Hz, 1H), 2.37 (s, 3H), 1.60 (d, J = 6.9 Hz, 0.73H), 1.52
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(d, J = 6.9 Hz, 3H). C NMR (75 MHz, CDCl3) δ (ppm) 194.1, 144.9, 135.6, 134.2, 132.2, 131.2,
130.2, 129.5, 128.9, 128.8, 128.6, 127.3, 125.4, 124.0, 78.1, 24.2, 21.8, 18.8.; Enantiomeric excess is
66% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm):
major rotamer: major isomer: tR = 12.1 min, minor isomer: tR = 14.1 min. minor rotamer: major isomer:
tR = 15.4 min, minor isomer: tR = 17.4 min.. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C20H19O4S
355.1004; found 355.1021.
(R)ꢀ 1ꢀ(naphthalenꢀ2ꢀyl)ꢀ1ꢀoxopropanꢀ2ꢀyl naphthaleneꢀ1ꢀsulfonate (3m). Prepared according to
the general procedure A. Reaction on 18.4 mg (0.10 mmol) of 1ꢀ(naphthalenꢀ2ꢀyl)propanꢀ1ꢀone (2j).
Eluent for the preparative TLC: heptane/MTBE 7/3, to afford, 26.6 mg of colorless oil, 68% yield with
two inseparable diastereoisomers (90/10). [α]22D ꢀ11.4 (c 1.0, CHCl3); IR 2927, 1695, 1362, 1306, 1179,
1
1127, 1017, 979, 918, 834, 804, 771, 678 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 8.59 (d, J = 8.4
Hz, 1H), 8.29 (s, 1H), 8.25 (d, J = 7.3 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.82 (dd, J = 15.8, 7.6 Hz, 4H),
7.76 (s, 2H), 7.66 – 7.40 (m, 7H), 6.00 (q, J = 6.9 Hz, 0.12H), 5.89 (q, J = 6.9 Hz, 1H), 1.70 (d, J = 6.9
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Hz, 0.5H), 1.63 (d, J = 6.9 Hz, 3H).13C NMR (75 MHz, CDCl3) δ (ppm) 194.6, 135.8, 135.6, 134.2,
132.3, 132.1, 131.1, 130.7, 130.2, 129.9, 129.1, 128.7, 128.5, 127.9, 127.3, 127.1, 125.2, 124.1, 124.0,
78.3, 19.0.; Enantiomeric excess is 66% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10,
flow rate = 1.0 mL/min, 254 nm): major rotamer: major isomer: tR = 13.4 min, minor isomer: tR = 16.6
min. minor rotamer: major isomer: tR = 18.3 min, minor isomer: tR = 21.0 min.. HRMS (ESIꢀTOF) m/z:
[M+H]+ Calcd for C23H19O4S 391.1004; found 391.0980.
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(R)ꢀ1ꢀoxoꢀ1ꢀphenylpropanꢀ2ꢀyl methanesulfonate (3n).11a Prepared according to the general
procedure B. Reaction on 13.4 mg (0.10 mmol) of propiophenone (2a). Eluent for the preparative TLC:
heptane/MTBE 7/3, to afford, 12.9 mg of colorless oil, 57% yield. [α]20D +23.8 (c 1.0, CHCl3); IR 2940,
1700, 1353, 1229, 1176, 975, 926, 701 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.94 (d, J = 7.3 Hz,
2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 6.05 (q, J = 7.0 Hz, 1H), 3.14 (s, 3H), 1.66 (d, J =
7.0 Hz, 3H).; Enantiomeric excess is 62% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 98/2,
flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 24.7 min, minor isomer: tR = 28.3 min.
(R)ꢀ2ꢀ[(diphenoxyphosphoryl)oxy]ꢀ1ꢀphenylpropanꢀ1ꢀone (3o).11a Prepared according to the
general procedure C. Reaction on 13.4 mg (0.10 mmol) of propiophenone (2a). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford, 24.2 mg of colorless oil, 63% yield. [α]22D ꢀ0.9 (c 1.0,
CHCl3); IR 3066, 1710, 1593, 1489, 1189, 959, 773 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 7.93 (d,
J = 7.5 Hz, 2H), 7.58 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.39 – 7.25 (m, 5H), 7.26 – 7.08 (m,
5H), 5.93 (p, J = 7.0 Hz, 1H), 1.61 (d, J = 6.9 Hz, 3H).; Enantiomeric excess is 62% determined by
HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR =
19.2 min, minor isomer: tR = 29.5 min.
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(R)ꢀ1ꢀ(naphthalenꢀ2ꢀyl)ꢀ1ꢀoxopropanꢀ2ꢀyl diphenyl phosphate (3p). Prepared according to the
general procedure C. Reaction on 18.4 mg (0.10 mmol) of 1ꢀ(naphthalenꢀ2ꢀyl)propanꢀ1ꢀone (2j). Eluent
for the preparative TLC: heptane/MTBE 7/3, to afford, 23.6 mg of colorless oil, 55% yield. [α]22D +16.3
(c 1.0, CHCl3); IR 2929, 1698, 1607, 1591, 1489, 1286, 1219, 1189, 1043, 1026, 1010, 959, 756, 689
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cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.51 (s, 1H), 8.07 – 7.86 (m, 5H), 7.63 (dt, J = 21.4, 7.1 Hz,
2H), 7.44 – 7.27 (m, 4H), 7.27 – 7.15 (m, 4H), 7.15 – 7.05 (m, 1H), 6.12 (p, J = 7.3 Hz, 1H), 1.72 (d, J
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= 6.7 Hz, 3H). C NMR (75 MHz, CDCl3) δ (ppm) 195.3, 136.0, 132.5, 131.4, 130.9, 130.0, 129.9,
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129.8, 129.1, 128.9, 127.9, 127.1, 125.6, 125.5, 124.3, 120.4, 120.3, 76.5, 76.4, 19.5, 19.5.;
Enantiomeric excess is 57% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 95/5, flow rate =
1.0 mL/min, 254 nm): major isomer: tR = 23.9 min, minor isomer: tR = 37.0 min. HRMS (ESIꢀTOF)
m/z: [M+Na]+ Calcd for C25H21O5NaP 455.1024; found 455.1035.
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(R)ꢀ1ꢀ(4ꢀfluorophenyl)ꢀ1ꢀoxopropanꢀ2ꢀyl diphenyl phosphate (3q). Prepared according to the
general procedure C. Reaction on 15.2 mg (0.10 mmol) of 4’ꢀfluoropropiophenone (2b). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford, 20.1 mg of colorless oil, 50% yield. [α]22D +3.9 (c 1.0,
CHCl3); IR 3065, 2926, 1778, 1697, 1591, 1489, 1307, 1219, 1188, 1167, 1127, 1083, 1010, 961, 755,
689 cmꢀ1; 1H NMR (300 MHz, CDCl3) δ (ppm) 8.00 – 7.82 (m, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.21 (t, J
= 7.1 Hz, 5H), 7.12 (d, J = 7.2 Hz, 3H), 7.04 (t, J = 8.3 Hz, 2H), 5.80 (p, J = 6.9 Hz, 1H), 1.58 (d, J =
6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ (ppm) 167.9, 150.5, 131.9, 131.8, 131.7, 130.0, 130.0,
129.8, 129.8, 125.7, 125.7, 120.4, 120.3, 120.3, 116.3, 116.0, 76.5, 76.4, 19.2.; Enantiomeric excess is
63% determined by HPLC (Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm):
major isomer: tR = 20.6 min, minor isomer: tR = 37.2 min. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for
C21H19FO5P 401.0954; found 401.0938.
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(R)ꢀ1ꢀoxoꢀ1ꢀ(pꢀtolyl)propanꢀ2ꢀyl diphenyl phosphate (3r). Prepared according to the general
procedure C. Reaction on 14.8 mg (0.10 mmol) of 4’ꢀmethylpropiophenone (2g). Eluent for the
preparative TLC: heptane/MTBE 7/3, to afford 23.2 mg of colorless oil, 59% yield. [α]22 +1.7 (c 1.0,
D
CHCl3); IR 3067, 2929, 1702, 1591, 1489, 1698, 1607, 1591, 1489, 1286, 1043, 1026, 1010, 959 ,756,
1
689 cmꢀ1; H NMR (300 MHz, CDCl3) δ (ppm) 7.82 (d, J = 7.8 Hz, 2H), 7.32 (dd, J = 14.3, 6.6 Hz,
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2H), 7.28 – 7.09 (m, 10H), 5.89 (p, J = 7.0 Hz, 1H), 2.40 (s, 3H), 1.59 (d, J = 6.7 Hz, 3H). C NMR
(75 MHz, CDCl3) δ (ppm) 150.6, 150.5, 144.9, 131.5, 130.0, 129.9, 129.8, 129.6, 129.0, 125.6, 125.5,
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120.4, 120.4, 120.3, 76.5, 76.4, 21.8, 19.5.; Enantiomeric excess is 56% determined by HPLC
(Chiralpak IA, Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 20.6 min,
minor isomer: tR = 35.6 min. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C22H22O5P 397.1205; found
397.1211.
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(R)ꢀ1ꢀoxoꢀ1ꢀphenylbutanꢀ2ꢀyl diphenyl phosphate (3s). Prepared according to the general
procedure C. Reaction on 14.8 mg (0.10 mmol) of 1ꢀphenylbutanꢀ1ꢀone (2i). Eluent for the preparative
TLC: heptane/MTBE 7/3, to afford 23.0 mg of colorless oil, 58% yield. [α]22D +5.1 (c 1.0, CHCl3); IR
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3067, 2976, 1702, 1591, 1489, 1291, 1220, 1189, 1059, 1025, 953, 776, 755, 689 cmꢀ1; H NMR
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(300 MHz, CDCl3) δ (ppm) 7.93 (d, J = 7.6 Hz, 2H), 7.59 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.4 Hz, 2H),
7.40 ꢀ 7.09 (m, 10H), 5.78 (q, J = 6.2 Hz, 1H), 2.15 – 1.86 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H). 13C NMR
(75 MHz, CDCl3) δ (ppm) 195.4, 150.7, 134.6, 133.8, 129.9, 129.8, 128.9, 128.8, 125.6, 125.5, 120.4,
120.3, 120.2, 81.5, 81.4, 26.9, 9.2.; Enantiomeric excess is 59% determined by HPLC (Chiralpak IA,
Heptane/iPrOH = 90/10, flow rate = 1.0 mL/min, 254 nm): major isomer: tR = 19.0 min, minor isomer:
tR = 42.7 min. HRMS (ESIꢀTOF) m/z: [M+H]+ Calcd for C22H22O5P 397.1205; found 397.1218.
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AUTHOR INFORMATION
Corresponding Authors
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*geraldine.masson@cnrs.fr
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Author Contributions
All authors have given approval to the final version of the manuscript.
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NOTES
The authors declare no competing financial interest.
ACKNOWLEDGMENT
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G.L thanks Saclay University for the doctoral fellowships; A.D. thanks ICSN and CNRS for financial
support and doctoral fellowships.
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SUPPORTING INFORMATION
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Selected NMR and HPLC spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
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(16) The absolute configuration of 1k was assigned by single crystal Xꢀray diffraction analysis, see
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