Synthesis and evaluation of C2-symmetric bis-sulfinamides as effective ligands in rhodium catalyzed addition of arylboronic acids to cycloalkenones

Article abstract of DOI:10.1016/j.tet.2016.07.024

Synthesis of novel C₂-symmetric 1,2- 1,3- and 1,4- bis-sulfinamides and their use as effective ligands in rhodium (I) catalyzed asymmetric conjugate addition of arylboronic acids to cyclohexenone and cyclopentenones is described. C₂-

Full text of DOI:10.1016/j.tet.2016.07.024

Accepted Manuscript
Synthesis and evaluation of C -symmetric bis-sulfinamides as effective ligands in
2
rhodium catalyzed addition of arylboronic acids to cycloalkenones
Omkar Revu, Manoj B. Uphade, Kavirayani R. Prasad
PII:
S0040-4020(16)30647-0
10.1016/j.tet.2016.07.024
TET 27920
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 April 2016
Revised Date: 1 July 2016
Accepted Date: 6 July 2016
Please cite this article as: Revu O, Uphade MB, Prasad KR, Synthesis and evaluation of C -
2
symmetric bis-sulfinamides as effective ligands in rhodium catalyzed addition of arylboronic acids to
cycloalkenones, Tetrahedron (2016), doi: 10.1016/j.tet.2016.07.024.
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ACCEPTED MANUSCRIPT
Synthesis and Evaluation of C2-symmetric Bis-Sulfinamides as Effective
Ligands in Rhodium Catalyzed Addition of Arylboronic Acids to
Cycloalkenones#
Omkar Revu, Manoj B. Uphade and Kavirayani R. Prasad*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
E-mail: prasad@orgchem.iisc.ernet.in FAX: +91-80-23600529
Abstract: Synthesis of novel C2-symmetric 1,2- 1,3- and 1,4- bis-sulfinamides and their use as
effective ligands in rhodium (I) catalyzed asymmetric conjugate addition of arylboronic acids to
cyclohexenone and cyclopentenones is described. C2-symmetry as well as chirality at the sulphur
center in the ligand is crucial for the high enentioselectivity in the 1,4-addition reaction. It was also
observed that the conjugate addition proceeded with good selectivity with Wilkinson’s catalyst as
the rhodium source.
Keywords: Conjugate addition, Chiral sulfinamides, C2-symmetry, Asymmetric catalysis
Introduction
The discovery of chiral diene/ phosphine rhodium complexes catalyze the enantioselective
conjugate addition of arylboronic acid to cyclohexenones by Hayashi and Miyura led to a virtual
explosion in the development of a number of chiral diene/ phosphine rhodium complexes for this
useful transformation.1 A plethora of publications describing the synthesis and screening of a
variety of chiral diene/ phosphine ligands in combination with the rhodium catalysts were reported
in literature.2 Recently, ligands containing chiral sulphur-olefin moieties are shown to exert
excellent enantioselectivity in the asymmetric conjugate addition of arylboronic acids to
cycloalkenones.3 A series of structurally diverse sulfoxides and sulfinamides embodied with an
olefin moiety were proved to be good ligands in the conjugate addition of arylboronic acids to
cycloalkenones (Fig-1) owing to their ease of preparation, stability and affinity to bind to metal
center. Although, a number of chiral sulfinamides comprising an alkene tether were tested for their
efficiency in the conjugate addition reactions, the efficiency of C2-symmetric sulfinamides was not
examined. Herein, we report the synthesis and evaluation of C2-symmetric 1,2, 1,3 and 1,4 bis-
sulfinamides 1-4 possessing a homoallyl tether as liagnds in rhodium catalyzed conjugate addition
of aryl boronic acids to unsaturated cyclic ketones. The sulfinamides with homoallyl tether were
chosen as the ligands as they are easy to synthesize from the established allylation of sulfinimines4
with excellent diastereoselectivity and would exert similar properties to the sulfur based olefin
ligands reported for rhodium catalyzed conjugate addition reactions.
Fig-1: Representative chiral sulfur-alkene ligands in Rh-catalyzed asymmetric conjugate addition
of arylboronic acids
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ACCEPTED MANUSCRIPT
Results and Discussion
At the outset, synthesis of the C2-symmetric 1,2-bis-sulfinamide 1a was attempted from the known
bis-sulfinmine 5 derived from glyoxal 6 using a procedure reported in literature.5 Although, Barbier
type allylation of the bis-imine 5 with allylbromide in presence of zinc was reported to produce a
single diastereomer 1a, we consistently observed the formation of three diastereomers 1a-c which
were separated by column chromatography. C2-symmetric diastereomers 1a and 1b were isolated in
37%, 4% respectively while the other diastereomer 1c was isolated in 30% yield. The
stereochemistry at the newly formed center in 1a and 1c was further confirmed by X-ray crystal
structure analysis.6 Ring closing metathesis of the diene in the bis-sulfinamide 1a afforded the 1,2-
bis-sulfinamido cyclohex-4-ene 4 in 87% yield. Similarly, addition of allylzinc bromide to the bis-
sulfinimine 8 derived from ortho-phthalaldehdye 9 afforded the C2-symmetric 1,4-bis-sulfinamide
3 in 40% yield as a single diastereomer (scheme-1).
Scheme-1: Synthesis of the ligands 1a-c, 3 and 4
Synthesis of the C2-symmetric 1,3-bis-sulfinamide 2 is accomplished by the following sequence.
Oxidation of the mono TBS ether 11 (prepared from 2,2-dimethyl 1,3-propane diol 10) to the
aldehyde and further condensation of the resultant aldehyde with (S)-tert-butane sulfinamide 7 in
presence of Ti(OEt)4 afforded the sulfinimine 12 in 88% yield. Barbier allylation of the sulfinimine
with allylbromide/Zn afforded the product sulfinamide 13 as a single diastereomer in 52% yield.
Deprotection of the TBS group in 13 furnished the alcohol 14 in 70% yield. Stereochemistry at the
newly formed stereogenic center in 13 is further confirmed by X-ray crystal structure analysis of
14.7 Oxidation of the alcohol 14 to the aldehyde and further condensation of the aldehyde with the
sulfinamide 7 afforded the sulfinimine 15 in 68% yield. Allylation with allylbromide/zinc furnished
the C2-symmetric 1,3-bis-sulfinamide 2 in 77% yield (Scheme-2).
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ACCEPTED MANUSCRIPT
Scheme-2: Synthesis of C2-symmetric 1,3-bis-sulfinamide 2 from 2,2-dimethyl-1,3-propanediol
After accomplishing the synthesis of the ligands 1-4, effect of these ligands in the conjugate
addition of phenylboronic acid 17 to cyclohexenone 16 in presence of rhodium catalysts was
examined. Thus, addition of phenylboronic acid to cyclohexenone in presence of 1 mol% of
[Rh(C2H4)2Cl]2 and 1 mol% of C2-symmetric 1,2-bis-sulfinamide ligand 1a afforded 3-phenyl
cyclohexanone in 92% ee and in 95% yield. Interestingly, the other diastereomeric C2-symmetric
1,2-bis-sulafinamide ligands 1b, 1c and 4 in presence of 1 mol% of [Rh(C2H4)2Cl]2 did not catalyze
the addition reaction. This observation indicate that perhaps, the match-mismatch pair of chirality
at the sulfur center of the sulfinamide and the chirality at the carbon bearing nitrogen in 1a-c plays
an important role in the enantio induction. Employing the 1,3-bis-sulfianmide 2 as ligand afforded
the product with 68% ee, while the C2-symmetric 1,4-bis-sulfinamide 3 provided the product with
70% ee albeit in 34% yield. Decreasing the loading of the catalyst [Rh(C2H4)2Cl]2 to 0.5 mol% and
0.3 mol% with 1a as the ligand did not really change the outcome of the enantioselectivity although
the yield of the reaction has dropped to 86% and 72% respectively (entries 7 & 8, table 1). It was
also observed that employing KOH as the base instead of K3PO4 furnished the product with similar
enantioselectivity (entry 9, table 1). Change in solvent from THF to 1,4-dioxane also afforded the
product with 95:5 enantiomeric ratio (entry 10, table 1), while employing DMF as solvent mitigated
the reaction completely clearly indicating the preference for ethereal solvents in the reaction. After
establishing the 1,2-bis-sulfinamide 1a as the suitable ligand in the addition of PhB(OH)2 to
cyclohexenone, effect of other rhodium complexes such as Wilkinson’s catalyst and [Rh(COD)Cl]2
in presence of the bis-sulfinamide 1a as ligand was examined. Accordingly, conducting the reaction
with 1 mol% [Rh(COD)Cl]2 furnished the product 3-phenyl cyclohexenone in quantitative yield
albeit in racemic form (entry 12, table 1). We presume that the displacement of ethylene ligand in
[Rh(C2H4)2Cl]2 with the bis-sulfinamide is facile, while the displacement of COD is not so facile
and hence the achiral catalyst [RhCl(COD)2]2 is predominant in accelerating the conjugate addition
resulting in the racemic product.8 Performing the reaction with 1 mol% of Wilkinsons’ catalyst did
not catalyze the reaction, while increasing the catalyst loading to 4 mol% afforded the product in
55% yield with 95:5 enantiomeric ratio (entry 14, table 1). Performing the reaction with 10 mol%
of Wilkinson’s catalyst decreased the reaction time and furnished the product phenyl
cyclohexanone in 90% yield with excellent enantiomeric 97:3 ratio (entry 16, table 1). It is worth
noting that the current study is perhaps the first example involving the use of Wilkinson’s catalyst
in asymmetric conjugate addition of PhB(OH)2 to cyclohexenone. Although Wilkinson’s catalyst
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ACCEPTED MANUSCRIPT
provided the required 1,4-additon product with good selectivity and high yield, owing to the high
amount of catalyst loading (10 mol%), we chose [Rh(C2H4)2Cl]2 in further optimization of the
conjugate addition reaction. All the results are summarized in table-1. In all cases, the product 3-
phenylcyclohexanone was obtained with R-configuration.
Table-1: Rhodium catalyzed asymmetric conjugate addition of PhB(OH)2 to cyclohexenone in
presence of bis-sulfianmide ligands 1-4.a
S.
No.
1
2
3
4
5
6
7
Rh-catalyst
Ligand
Time (h)
Solvent
Yield (%)b
erc
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (0.5 mol%)
[Rh(C2H4)2Cl]2 (0.3 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)e
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(C2H4)2Cl]2 (1 mol%)
[Rh(COD)Cl]2 (1 mol%)
[Rh(PPh3)3Cl] (1 mol%)
[Rh(PPh3)3Cl] (4 mol%)
[Rh(PPh3)3Cl] (6 mol%)
[Rh(PPh3)3Cl] (10 mol%)
1
3
3
3
3
3
3
3
3
3
3
2
24
10
10
4
THF
THF
THF
THF
THF
THF
THF
THF
THF
95
96:4
-
-
84:16
85:15
-
93:7
95:5
96:4
95:5
1a
1b
1c
2
3
4
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
d
-
d
-
74%
34%
d
-
86%
72%
91%
85%
8
9
10
11
12
13
14
15
16
1,4-dioxane
DMF
THF
d
-
98%
racemic
-
95:5
96:4
d
THF
THF
THF
THF
-
55%
70%
90%
97:3
aAll reactions were performed with 1 mol% of bis-sulfinamide 1a-4 and 0.5 eq of K3PO4. Yield
refer to isolated yield of column chromatography. cEnantiomeric ratio (er) was estimated by HPLC
analysis on a chiral CHIRALCEL-OD-H column. dNo appreciable reaction was observed. eKOH is
used as base instead of K3PO4.
b
To determine whether chirality at the sulphur center is essential and plays a role in the enantio
induction, synthesis of the following ligands possessing/ lacking chirality at sulphur were prepared.
Thus, reaction of the bis-sulfinamide 1a with m-CPBA in dichloromethane afforded the bis-
sulfonamide 19, which lacks chirality at sulfur in 50% yield along with the mono sulfonamide 20
(with one of the sulfur centers being chiral) in 30% yield (Scheme-3). The sulfinamide 21 bearing
chirality only at sulfur was prepared by reduction of the sulfinimine 5 with NaBH4 and allylation of
the resultant bis-sulfinamide.
Scheme-3: Synthesis of the bis-sulfonamide 19 and the sulfonamides 20-21
4

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Addition of PhB(OH)2 to cyclohexenone, in presence of the bis-sufonamide ligand 19 possessing
chirality at the carbon centers afforded racemic 3-phenylcyclohexanone 18 in mere 20% yield,
while the mono sulfinamide 20 devoid of C2-symmetry did not catalyze the addition reaction.
Interestingly, the C2-symmetric bis-sulfinamide 21 comprising chirality only at the sulphur center
afforded product in 79% yield with 40% ee, clearly highlighting that the chirality at the sulphur
center as well as the C2-symmetry is essential for the enantioselectivity observed in the reaction.
This experiment provides indirect evidence that match pair chirality at sulphur, nitrogen bearing
carbon and also the C2-symmetry in the ligand is essential for the good enantioselectivity in the
reaction.
With the optimized reaction conditions i.e. 1 mol% of C2-symmetric homoallylic sulfinamide
ligand 1a, 1 mol% [Rh(C2H4)2Cl]2 catalyst and 0.5 eq of K3PO4 as base, generality and scope of the
reaction was examined with the 1,4-addition of different arylboronic acids to cyclohexenone and
cyclopentenone. Thus addition of 3-fluorophenyl, 3-methylphenyl and 4-methoxyphenylboronic
acids to cyclohexenone proceeded smoothly to yield the corresponding 3-arylcyclohexenones in
high yields and good enantioselectivities. Addition of phenylboronic acid as well as 4-
methoxypheyl and 4-tert-butylphenyl boronic acids to cyclopentenone afforded the 3-aryl
cyclopentenones in good yield with excellent enantiomeric ratios (Table-2). Employing 2-
fluorophenyl, 2-bromophenyl and 4-bromophenyl, 4-trifluoromethyl phenyl, 2-methylphenyl, 2-
formylphenyl boronic acids in the addition reaction either with cyclohexenone or cyclopetenone did
not afford the product.
Table-2: Asymmetric conjugate addition of arylboronic acids to cycloalkenones
S. No.
Alkenone
Ar
Yielda %
erb
96:4
95:5
98:2
96:4
99:1
94:6
86:14
1
2
3
4
5
cyclohexenone
cyclohexenone
cyclohexenone
cyclohexenone
cyclopentenone
cyclopentenone
cyclopentenone
Phenyl
95
93
70
93
95
99
81
3-methylphenyl
3-fluorophenyl
4-methoxyphenyl
Phenyl
6
4-methoxyphenyl
7c
4-tbutyl-phenyl
aAll reactions were performed with 1mol% of [Rh(C2H4)2Cl]2 and 1 mol% of bis-sulfinamide 1a as
a chiral ligand in THF at 60 °C for 1h. Yields refer to isolated yield of column chromatography.
bEnantiomeric ratio (er) was estimated by HPLC analysis on a chiral CHIRALCEL-OD-H column.
cReaction was performed with Wilkinson’s catalyst. No appreciable reaction was observed with
[Rh(C2H4)2Cl]2 as the catalyst.
Conclusion
In conclusion, a systematic study of the synthesis and evaluation of novel homoallylic C2-
symmetric bis-sulfinamides as effective ligands in rhodium catalyzed asymmetric addition of
arylboronic acids to cyclohexenone and cyclopentenones is presented. It was found that amongst
the symmetric 1, 2; 1,3; 1,4-bis sulfinamides the C2-symmetric sulfinamide derived from glyoxal
was a better catalyst and exerted high enantioselectivity in the conjugate addition reaction. It was
5

ACCEPTED MANUSCRIPT
also observed that amongst the 1,2-bis-sulfinamide ligands, the match pair chirality at the sulphur
center, nitrogen bearing carbon as well as the C2-symmetry in the ligand is essential for the high
enentioselectivity of the 1,4-addition products. Interestingly, the reaction also proceeds with very
good enentioselectivity with Wilkinson’s catalyst, which was hitherto not examined in asymmetric
Rh-catalyzed conjugate addition of arylaboronic acids to enones.
Experimental:
General information: Column chromatography was performed on silica gel, Acme grade 100-200
mesh and neutral alumina, SD-Fine grade. TLC plates were visualized either with UV, in an iodine
chamber, or with phosphomolybdic acid spray. All reagents were purchased from commercial
sources and were used without additional purification. THF was freshly distilled over Na-
1
benzophenone ketyl. Melting points were uncorrected. H NMR and 13C NMR spectra were
recorded on a 400 MHz machine in CDCl3 or (CD3)2SO as solvent with TMS as reference unless
otherwise indicated. Unless stated otherwise, all reactions were performed under inert atmosphere.
All specific rotations were determined at 24 °C. HRMS was obtained using a micromass-QTOF
spectrometer using electrospray ionization (ESI).
Preparation of (SS)-N,N'-((1E,2E)-ethane-1,2-diylidene)bis(2-methylpropane-2-sulfinamide)
(5): To a solution of (S)-tert-butane sulfinamide 7 (1.21 g, 10 mmol) in CH2Cl2 (40 mL) were
added anhydrous CuSO4 (6.4 g, 40 mmol) followed by 40% aq. glyoxal 6 (0.72 mL, 5 mmol). The
reaction mixture was stirred for 2 days at rt. After completion of the reaction (TLC), it was filtered
through a pad of Celite and the celite pad was washed with CH2Cl2 (30 mL). The filtrate was
concentrated in vacuo to afford crude residue which was purified by silica gel column
chromatography with petroleum ether/EtOAc (4:1) as eluent to afford the bis-sulfinimine 5 (0.76 g,
58%) as an yellow solid. Rf 0.60 (25% EtOAc/petroleum ether); mp: 63-65 °C; [α]D: +610.8 (c 0.6,
1
CHCl3); IR (KBr): 2960, 2926, 1695, 1576, 1085 cm-1; H NMR (400 MHz, CDCl3):
2H), 1.27 (s, 18H); C NMR (100 MHz, CDCl3):
δ 8.47 (s,
13
δ 159.3, 58.7, 22.5 (3×CH3); HRMS: M+Na
found: 287.0867. C10H20N2O2S2+Na requires: 287.0864.
Preparation
of
(SS)-N,N'-((4S,5S)-octa-1,7-diene-4,5-diyl)
bis
(2-methylpropane-2-
sulfinamide) (1a): To a stirred suspension of bis-sulfinimine 5 (0.20 g, 0.75 mmol) and zinc
powder (0.36 g, 5.30 mmol) in THF was added allylbromide (0.39 mL, 4.54 mmol) at 0 °C under
argon atmosphere and the reaction mixture was stirred at 0 °C for 3 h. After completion of the
reaction (TLC), it was quenched with sat. NH4Cl solution and was filtered through a short pad of
celite and the celite pad was washed with EtOAc. The filtrate was washed with water (10 mL)
followed by brine (10 mL) and the aqueous layer was extracted with EtOAc. The combined organic
layer was dried over anhyd. Na2SO4. Evaporation of the solvent followed by silica gel column
chromatography of the residue with petroleum ether/EtOAC (2:8) as eluent afforded 1a as a white
solid in 37% yield, 1b as a viscous mass in 4% yield and 1c as a white solid in 30% yield. Rf 0.70
(80% EtOAc/Petrolium ether); Mp: 65-67 °C; [α]D: +159.9 (c 1.0, CHCl3); IR (KBr): 3203, 2926,
1
1644, 1470, 1437 cm-1; H NMR (400 MHz, CDCl3):
δ 5.77 (td, J = 17.0, 7.0 Hz, 2H), 5.25-5.05
13
(m, 6H), 3.21 (dd, J = 14.6, 7.0 Hz, 2H), 2.60-2.44 (m, 2H), 2.44-2.30 (m, 2H), 1.25 (s, 18H); C
6

ACCEPTED MANUSCRIPT
NMR (100 MHz, CDCl3):
371.1805. C16H32N2O2S2+Na requires 371.1803.
data of 1b: [α]D: +36.2 (c 0.45, CHCl3); IR (Neat): 3203, 2926, 1644, 1470, 1437 cm-1; H NMR
(400 MHz, CDCl3): 5.78 (ddt, J = 17.0, 10.2, 6.8 Hz, 2H), 5.20-5.02 (m, 6H), 3.31 (dd, J = 9.2,
4.6 Hz, 2H), 2.57 (dt, J = 15.2, 7.8 Hz, 2H), 2.48-2.38 (m, 2H), 1.25 (s, 18H); 13C NMR (100 MHz,
CDCl3): 135.0, 117.1, 60.4, 56.1, 35.8, 22.9 (3×CH3); HRMS: M+Na found: 371.1805
δ 134.7, 117.7, 60.9, 56.1, 40.3, 23.0 (3×CH3); HRMS: M+Na found:
1
δ
δ
C16H32N2O2S2+Na requires: 371.1803;.
data of 1c: mp: 88-89 °C; [α]D: +160.7 (c 1.05, CHCl3); IR (KBr): 3203, 2926, 1644, 1470, 1437
1
cm-1; H NMR (400 MHz, CDCl3):
δ 6.01-5.85 (m, 1H), 5.77 (ddt, J = 17.0, 10.0, 6.8 Hz, 1H),
5.22-5.01 (m, 4H), 4.62 (d, J = 7.2 Hz, 1H), 4.15 (d, J = 9.8 Hz, 1H), 3.68-3.54 (m, 1H), 3.45-3.35
13
(m, 1H), 2.55-2.23 (m, 4H), 1.25 (s, 9H), 1.21 (s, 9H); C NMR (100 MHz, CDCl3):
δ 135.14,
134.96, 117.8, 117.3, 61.2, 59.0, 56.3, 56.2, 35.8, 35.7, 22.8 (3×CH3), 22.7 (3×CH3); HRMS:
M+Na found: 371.1805 C16H32N2O2S2+Na requires: 371.1803.
Preparation of (SS)-N,N'-((1S,2S)-cyclohex-4-ene-1,2-diyl) bis (2-methylpropane-2-
sulfinamide) (4): To a stirred solution of the diene 1a (0.11 g, 0.32 mmol) in dry CH2Cl2 (32 mL)
was added Grubbs’ first generation catalyst (0.026 g, 0.032 mmol) under argon atmosphere and the
reaction mixture was refluxed for 3 h. After completion of the reaction (TLC), most of the solvent
was evaporated off and the crude residue thus obtained was purified by silica gel column
chromatography using petroleum ether/EtOAc (1:4) as eluent to afford 4 (0.09 g, 87%) as a white
solid. Rf 0.40 (80% EtOAc/petroleum ether); mp: 180-182 °C; [α]D: +223.5 (c 1.0, CHCl3); IR
1
(KBr): 3223, 2897, 1416, 1038 cm-1; H NMR (400 MHz, CDCl3):
δ 5.57 (s, 2H), 4.51 (s, 2H),
13
3.34 (s, 2H), 2.55 (d, J = 16.2 Hz, 2H), 2.20-2.03 (m, 2H), 1.24 (s, 18H); C NMR (100 MHz,
CDCl3): 124.8, 56.1, 55.6, 34.8, 22.9 (3×CH3); HRMS M+Na found: 343.1490.
δ
C14H28N2O2S2+Na requires: 343.1490.
Preparation of (SS)-N,N'-((1E,1'E)-1,2-phenylenebis(methanylylidene))bis(2-methylpropane-
2-sulfinamide) (8): To a stirred solution of (S)-tert-butane sulfinamide 7 (0.145 g, 1.2 mmol) in
CH2Cl2 (3 mL) were added titanium tetraethoxide (0.52 mL, 2.5 mmol) followed by o-
pthalaldehyde 9 (0.06 g, 0.45 mmol) at room temperature and was stirred at the same temperature
for 6h. After completion of the reaction (TLC), it was quenched with sat. NH4Cl solution and was
extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were washed with brine (5 mL)
and dried over anhyd. Na2SO4. The crude residue obtained after evaporation of the solvent was
purified by silica gel column chromatography using petroleum ether/EtOAc (8:2) as eluent to
afford 8 (0.10 g, 66%) as a yellow oil; Rf 0.70 (60% EtOAc/petroleum ether); [α]D: +185.0 (c 0.5,
1
CHCl3); IR (Neat): 2925, 1728, 1608, 1459, 1365 cm-1; H NMR (400 MHz, CDCl3):
δ 9.17 (s,
13
2H), 7.96 (d, J = 4.4 Hz, 2H), 7.63 (d, J = 3.6 Hz, 2H), 1.30 (s, 18H); C NMR (100 MHz,
CDCl3):
δ 162.3, 133.6, 131.9, 131.2, 57.9, 22.6 (3×CH3); HRMS: M+Na found: 363.1175,
C16H24N2O2S2+Na requires 363.1177;.
7

ACCEPTED MANUSCRIPT
Preparation of (SS)-N,N'-((1S,1'S)-1,2-phenylenebis(but-3-ene-1,1-diyl))bis(2-methylpropane-
2-sulfinamide) (3): To a stirred solution of the bis-sulfinimine 8 (0.040, 0.12 mmol) in THF (2
mL) was added a freshly prepared solution of allylzinc bromide (0.36 mL of 1 M solution in THF,
0.36 mmol) at −78 °C dropwise under argon atmosphere. After the reaction was complete (TLC), it
was quenched with sat. NH4Cl solution and extracted EtOAc (2×10 mL). The combined organic
layer was washed with brine (10 mL) and dried over anhyd. Na2SO4. The crude residue obtained
after evaporation of the solvent was purified by silica gel column chromatography using petroleum
ether/EtOAc (4:3) as eluent to afford 3 (0.020 g, 40%) as a viscous mass; Rf 0.40 (75%
1
EtOAc/petroleum ether); [α]D: +199.0 (c 0.7, CHCl3); IR (Neat): 3436, 2921, 1639, 1364 cm-1; H
NMR (400 MHz, CDCl3):
δ 7.44 (d, J = 3.6 Hz, 2H), 7.29 (d, J = 5.4 Hz, 2H), 5.86 (ddd, J = 17.6,
14.8, 9.0 Hz, 2H), 5.34-5.14 (m, 4H), 4.86 (d, J = 4.2 Hz, 2H), 3.81 (s, 2H), 2.86-2.69 (m, 2H),
13
2.52-2.35 (m, 2H), 1.21 (s, 18H); C NMR (100 MHz, CDCl3):
δ 139.3, 134.3, 127.4, 127.2,
119.6, 55.7, 51.0, 43.4, 22.6 (3×CH3); HRMS M+Na found: 447.2117. C22H36N2O2S2+Na requires:
447.2116;
Preparation of 3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropan-1-ol (11): To a stirred
solution of the diol 10 (1.00 g, 9.60 mmol) in dry THF (10 mL) was added NaH (0.42 g of 60%
dispersed in mineral oil, 2.0 mmol) at 0 °C under nitrogen atmosphere. The reaction mixture was
stirred at the same temperature for 30 min. TBSCl (1.043 g, 9.60 mmol) was then added slowly to
the reaction mixture and was stirred for 4 h at room temperature. After completion of the reaction
(TLC), it was cautiously quenched by addition of ice cold water. The reaction mixture was then
poured into water (20 mL) and was extracted with EtOAc (2×20 mL). The combined organic layer
was washed with brine (15 mL) and dried over anhyd. Na2SO4. The crude residue obtained after
evaporation of the solvent was purified by column chromatography using petroleum ether/EtOAc
(20:1) as eluent to afford 11 (1.45 g, 70%) as a colorless oil. Rf 0.50 (5% EtOAc/petroleum ether);
1
IR (Neat): 3368, 2860, 1468, 1096 cm-1; H NMR (400 MHz, CDCl3):
δ
3.42 (s, 4H), 2.99 (d, J =
72.4, 71.9,
13
4.8 Hz, 1H), 0.86 (s, 9H), 0.84 (s, 6H), 0.03 (s, 6H); C NMR (100 MHz, CDCl3):
δ
36.3, 25.7 (3×CH3), 21.3 (2×CH3), 18.1, −5.7 (2×CH3); HRMS M+Na found: 241.1600.
C11H26O2Si+Na requires: 241.1600.
Preparation of (SS, E)-N-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropylidene)-2-
methylpropane-2-sulfinamide (12): To a stirred solution of 11 (1.0 g, 4.58 mmol) in EtOAc (10
mL) was added IBX (3.85 g, 13.0 mmol) and the resulting suspension was refluxed for 6 h. The
reaction mixture was cooled to room temperature; water (2 mL) was added and stirred for 10 min.
The clear organic layer was passed through a short pad of Celite and the Celite pad was washed
with EtOAc (30 mL). The organic layer was washed with sat. NaHCO3 solution (2×15 mL),
followed by brine (20 mL) and dried over anhydrous Na2SO4. Removal of solvent under reduced
pressure yielded the crude aldehyde, which was used in the next step without further purification.
To a stirred solution of the aldehyde (obtained above) in CH2Cl2 (20 mL) were added (S)-tert-
butane sulfinamide 7 (0.67 g, 5.49 mmol) followed by titanium tetraethoxide (2.88 mL, 13.74
8

ACCEPTED MANUSCRIPT
mmol) at room temperature and was stirred at same temperature. After completion of the reaction
(TLC), it was quenched by addition of sat.NH4Cl solution and was extracted with EtOAc (2×20
mL). The combined organic layer was washed with brine (10 mL) and dried over anhyd. Na2SO4.
The crude residue obtained after evaporation of the solvent was purified by silica gel column
chromatography using petroleum ether/EtOAc (9:1) as eluent to afford 12 (1.29 g, 88%) as a
colorless oil; Rf 0.30 (5% EtOAc/petroleum ether); [α]D: +141.4 (c 1.0, CHCl3); IR (Neat): 2932,
2859, 1729, 1621, 1468 cm-1; 1H NMR (400 MHz, CDCl3):
(s, 9H), 1.11 (s, 3H), 1.09 (m, 3H), 0.85 (s, 9H), 0.01 (s, 6H); C NMR (100 MHz, CDCl3):
δ 7.95 (s, 1H), 3.64-3.47 (m, 2H), 1.17
13
δ
174.4, 70.0, 56.5, 43.4, 25.3 (3×CH3), 22.3 (3×CH3), 21.7, 21.5, 18.2, −5.6 (2×CH3); HRMS M+Na
found: 342.1899. C15H33NO2SSi+Na requires: 342.1899.
Preparation
of
(SS)-N-((S)-1-((tert-butyldimethylsilyl)oxy)-2,2-dimethylhex-5-en-3-yl)-2-
methylpropane-2-sulfinamide (13): To a stirred solution of sulfinimine 12 (1.10 g, 3.45 mmol) in
THF (10 mL) was added a freshly prepared solution of allylzinc bromide (3.79 mL of 1M solution
in THF, 3.79 mmol) at −78 °C dropwise under argon atmosphere. After the reaction was complete
(TLC), it was quenched by addition of sat. NH4Cl solution and was extracted with EtOAc (2×20
mL). The combined organic layer was washed with brine (20 mL) and dried over anhyd. Na2SO4.
The crude residue obtained after evaporation of the solvent was purified by silica gel column
chromatography using petroleum ether/EtOAc (5:2) as eluent to afford 13 (0.64 g, 52%) as a
colorless oil; Rf 0.40 (30% EtOAc/petroleum ether); [α]D: +36.4 (c 1.1, CHCl3); IR (Neat): 2955,
2860, 1640, 1469, 1075 cm-1; 1H NMR (400 MHz, CDCl3):
δ 6.11-5.89 (m, 1H), 5.13 (s, 1H), 5.09
(d, J = 6.8 Hz, 1H), 3.46 (d, J = 9.6 Hz, 1H), 3.39 (d, J = 7.2 Hz, 1H), 3.32-3.24 (m, 1H), 3.27 (d, J
= 9.6 Hz, 1H), 2.60-2.46 (m, 1H), 2.36-2.18 (m, 1H), 1.21 (s, 9H), 0.89 (s, 12H), 0.84 (s, 3H), 0.03
13
(s, 6H); C NMR (100 MHz, CDCl3):
δ 136.3, 117.6, 69.8, 60.9, 56.2, 40.2, 36.1, 25.9 (3×CH3),
22.9 (3×CH3), 22.3, 21.6, 18.3, −5.5, −5.6; HRMS M+Na found: 384.2371. C18H39NO2SSi+Na
requires: 384.2368.
Preparation
of
(SS)-N-((S)-1-hydroxy-2,2-dimethylhex-5-en-3-yl)-2-methylpropane-2-
sulfinamide (14): To a pre-cooled (0 °C) solution of the TBS ether 13 (0.59 g, 1.60 mmol) in dry
THF (5 mL) was added TBAF (2.0 mL of 1.0 M solution in THF, 2 mmol) dropwise under nitrogen
atmosphere. The reaction mixture was warmed to room temperature and stirred at the same
temperature for 1 h. After completion of the reaction (TLC), the reaction mixture was poured into
ice cold water (20 mL) and was extracted with EtOAc (2×20 mL). The combined organic layer was
washed with brine (15 mL) and dried over anhydrous Na2SO4. Most of the solvent was removed in
vacuo and the resulting crude residue was purified by silica gel column chromatography using
petroleum ether/EtOAc (1:4) as eluent to afford the alcohol 14 (0.28 g, 70%) as a white solid; Rf
0.40 (75% EtOAc/petroleum ether); mp: 69-71 °C; [α]D: +68.8 (c 1.1, CHCl3); IR (KBr): 3239,
3162, 2957, 1669, 1421 cm-1; 1H NMR (400 MHz, CDCl3):
δ 5.95 (td, J = 17.0, 7.2 Hz, 1H), 5.23-
5.08 (m, 2H), 3.58 (dd, J = 10.8, 3.6 Hz, 1H), 3.45 (s, 1H), 3.41-3.27 (m, 2H), 2.62-2.50 (m, 1H),
13
2.32-2.20 (m, 1H), 1.91 (bs, 1H), 1.24 (s, 9H), 0.99 (s, 3H), 0.87 (s, 3H); C NMR (400 MHz,
CDCl3):
δ 136.1, 118.0, 69.7, 60.4, 56.5, 39.9, 36.0, 22.9 (3×CH3), 22.7, 21.1; HRMS M+Na
found: 270.1500. C12H25NO2S+Na requires 270.1504.
9

ACCEPTED MANUSCRIPT
Preparation
of
(SS)-N-((SS,E)-3-(((S)-tert-butylsulfinyl)amino)-2,2-dimethylhex-5-en-1-
ylidene)-2-methylpropane-2-sulfinamide (15): To a stirred solution of the alcohol 14 (0.063 g,
0.25 mmol) in dry CH2Cl2 (2 mL) were added NaHCO3 (0.040 g, 0.50 mmol) and Dess-Martin
periodinane (0.16 g, 0.38 mmol) at 0 °C under nitrogen atmosphere. The reaction mixture was
warmed to room temperature and was stirred at room temperature for 1 h. After completion of the
reaction (TLC), it was quenched by addition of saturated solutions of NaHCO3 (5 mL) and Na2S2O3
(5 mL). The aqueous phase was extracted with EtOAc (2×10 mL). The combined organic layers
were washed with brine (10 mL), dried over anhyd.Na2SO4 and concentrated. The crude aldehyde
thus obtained as colourless oil was used as such in the next step without further purification.
To a stirred solution of the aldehyde (obtained above) in CH2Cl2 (5 mL) were added (S)-tert-butane
sulfinamide 7 (0.032 g, 0.25 mmol) followed by titanium tetraethoxide (0.16 mL, 0.76 mmol) at
room temperature and was stirred at same temperature. After completion of the reaction (TLC), it
was quenched by addition of sat.NH4Cl solution and was extracted with EtOAc (2×10 mL). The
combined organic layer was washed with brine (10 mL) and dried over anhyd. Na2SO4. The crude
residue obtained after evaporation of the solvent was purified by silica gel column chromatography
using petroleum ether/EtOAc (2:3) as eluent to afford 15 (0.058 g, 68%) as a colorless solid; Rf
0.30 (50% EtOAc/petroleum ether); mp: 59-61 °C; [α]D: +252.3 (c 1.0, CHCl3); IR (KBr): 3380,
1
2312, 1589, 1339, 1018 cm-1; H NMR (400 MHz, CDCl3):
δ 7.98 (s, 1H), 5.87 (td, J = 16.8, 7.2
Hz, 1H), 5.25-5.08 (m, 2H), 3.66-3.31 (m, 2H), 2.77-2.40 (m, 1H), 2.40-2.11 (m, 1H), 1.40-1.15
13
(m, 24H); C NMR (100 MHz, CDCl3):
δ 174.1, 134.7, 118.8, 61.7, 56.7, 56.5, 46.0, 36.9, 23.3,
22.8 (3×CH3), 22.3 (3×CH3), 21.9; HRMS M+Na found: 371.1806. C16H32N2O2S2+Na requires:
371.1803.
Preparation of (SS)-N,N'-((4S,6S)-5,5-dimethylnona-1,8-diene-4,6-diyl) bis (2-methylpropane-
2-sulfinamide) (2): To a stirred solution of sulfinimine 15 (0.055 g, 0.16 mmol) in THF (2 mL)
was added freshly prepared solution of allylzinc bromide (0.32 mL of 1 M solution in THF, 0.32
mmol) at −78 °C dropwise under argon atmosphere. The reaction mixture was slowly warmed to
room temperature and was attired at rt. After the reaction was complete (TLC), it was quenched by
addition of sat.NH4Cl solution and was extracted with EtOAc (2×10 mL). The combined organic
layer was washed with brine (10 mL) and dried over anhyd. Na2SO4. The crude residue obtained
after evaporation of the solvent was purified by silica gel column chromatography using petroleum
ether/EtOAc (1:4) as eluent to afford 2 (0.047 g, 77%) as a white solid; Rf 0.40 (80%
EtOAc/petroleum ether); mp: 147-149 °C; [α]D: +96.4 (c 1.0, CHCl3); IR (KBr): 3217, 2953, 1468,
1424, 1036 cm-1; 1H NMR (400 MHz, CDCl3):
3.39 (dd, J = 11.6, 7.6 Hz, 2H), 3.21 (d, J = 7.6 Hz, 2H), 2.75-2.45 (m, 2H), 2.21 (dt, J = 14.8, 7.6
Hz, 2H), 1.26 (s, 18H), 0.88 (s, 6H); 13C NMR (100 MHz, CDCl3):
135.3, 118.3, 60.0, 56.6, 43.8,
δ 5.95 (td, J = 17.2, 7.2 Hz, 2H), 5.24-5.10 (m, 4H),
δ
35.8, 23.0 (3×CH3), 19.9; HRMS M+Na found: 413.2276. C19H38N2O2S2+Na requires 413.2272.
10

ACCEPTED MANUSCRIPT
m-CPBA, CH2Cl2
S
NH HN
S
O
S
NH HN
S
S
NH HN
S
O
0 °C to rt, 2 h
O
O
O
O
O
O
O
1a
19
20
Preparation of N,N'-((4S,5S)-octa-1,7-diene-4,5-diyl)bis(2-methylpropane-2-sulfonamide)
(19): To a stirred solution of 1a (0.037 g, 0.11 mmol) in CH2Cl2 (2 mL) at 0 °C was added
NaHCO3 (0.026 g, 0.32) and 3-chloroperbenzoic acid (0.040 g, 0.23 mmol). The reaction mixture
was slowly warmed to room temperature and was stirred at rt for 40 min. After the reaction was
complete (TLC), it was washed with a mixture of a solution of sat. NaHSO3 (5 mL) and NaHCO3
(5 mL). The aqueous layer was extracted with EtOAc (2 × 10 mL). The combined organic layer
was washed with brine (10 mL), dried over anhydrous Na2SO4. Evaporation of solvent followed by
silica gel column chromatography of the crude residue with petroleum ether/EtOAc (3:2) as eluent
afforded the bis-sulfone 19 (0.020 g, 50%) as a white solid and mono sulfone 20 (0.012 g, 30%) as
a white solid. Data for 19: Rf 0.50 (40% EtOAc/petroleum ether); mp: 196-198 °C; [α]D: −5.7 (c
1
0.7, CHCl3); IR (KBr): 2983, 1457, 1295, 1063, 958 cm-1; H NMR (400 MHz, CDCl3):
δ 5.95-
5.73 (m, 2H), 5.20 (dd, J = 13.6, 6.4 Hz, 4H), 4.52 (d, J = 8.8 Hz, 2H), 3.66-3.49 (m, 2H), 2.68-
2.53 (m, 2H), 2.45-2.28 (m, 2H), 1.41 (s, 18H); 13C NMR (100 MHz, CDCl3):
δ
133.2, 119.4, 60.2,
56.2, 37.1, 24.3 (3×CH3); HRMS M+Na found: 403.1702. C16H32N2O4S2+Na requires: 403.1701.
N-((4S,5S)-5-(((SS)-tert-butylsulfinyl)amino)octa-1,7-dien-4-yl)-2-methylpropane-2-
sulfonamide (20): mp: 118-120 °C; [α]D: +28.6 (c 1.0, CHCl3); IR (KBr): 3256, 2401, 1727, 1624,
1
1578 cm-1; H NMR (400 MHz, CDCl3):
δ 5.88-5.68 (m, 2H), 5.52 (d, J = 9.6 Hz, 1H), 5.27-5.03
(m, 4H), 4.22 (d, J = 10.0 Hz, 1H), 3.65-3.50 (m, 1H), 3.40-3.19 (m, 1H), 2.49 (t, J = 7.4 Hz, 2H),
13
2.41 (t, J = 6.8 Hz, 2H), 1.42 (s, 9H), 1.26 (s, 9H); C NMR (100 MHz, CDCl3):
δ 134.4, 134.0,
118.8, 118.0, 60.0, 59.4, 56.6, 55.7, 39.4, 39.3, 24.2 (3×CH3), 22.8 (3×CH3); HRMS M+Na found
387.1753. C16H32N2O3S2+Na requires 387.1752.
Preparation of (SS)-N,N'-(ethane-1,2-diyl)bis(N-allyl-2-methylpropane-2-sulfinamide) (21):
To a stirred solution of the bis-sulfinimine 5 (0.15 g, 0.57 mmol) in MeOH (2 mL) was added
NaBH4 (0.055 g, 0.1.44 mmol) portionwise at 0 °C and was stirred at the same temperature. After
the reaction was complete ( 30 min) (TLC), most of the solvent was removed under reduced
pressure, water (10 mL) was added to the reaction mixture and was extracted with EtOAc (2×20
mL). The combined organic layer was washed with brine (10 mL), dried over anhyd. Na2SO4.
Evaporation of solvent followed by silica gel column chromatography of the crude residue with
petroleum ether/EtOAc (1:9) as eluent afforded the bis-sulfinamide (0.12 g, 80%) as a white solid.
Rf 0.20 (100% EtOAc); mp: 196-198 °C; [α]D: +129.0 (c 1.05, CHCl3); IR (KBr): 2983, 1457,
1
1295, 1063, 958 cm-1; H NMR (400 MHz, CDCl3):
δ
4.59 (s, 2H), 3.41 (d, J = 8.8 Hz, 2H), 3.30
55.8, 47.1, 22.6 (3×CH3);
13
(d, J = 7.6 Hz, 2H), 1.24 (s, 18H); C NMR (100 MHz, CDCl3):
δ
HRMS M+Na found: 291.1176. C10H24N2O2S2+Na requires: 291.1177.
To a stirred solution of the bis-sulfinamide (0.076 g, 0.28 mmol) (obtained above) in dry DMF (2
mL) was added NaH (0.034 g of 60% dispersed in mineral oil, 0.85 mmol) at 0 °C under nitrogen
atmosphere and stirred for 1 h at same temperature. Allyl bromide (0.10 mL, 1.12 mmol) was
introduced into the reaction mixture dropwise at 0 °C and the reaction mixture was slowly warmed
to room temperature. After completion of the reaction (TLC), it was quenched by addition of
sat.NH4Cl solution and was extracted with EtOAc (2×10 mL). The combined organic layer was
11

ACCEPTED MANUSCRIPT
washed with brine (5 mL) and dried over anhyd. Na2SO4. The crude residue obtained after
evaporation of the solvent was purified by silica gel column chromatography using petroleum
ether/EtOAc (7:3) as eluent to afford 21 (0.08 g, 82%) as a colorless solid; Rf 0.70 (60%
EtOAc/petroleum ether); mp: 62-63 °C; [α]D: −86.9 (c 1.0, CHCl3); IR (KBr): 2918, 1471, 1422,
1353, 1065 cm-1; 1H NMR (400 MHz, CDCl3):
= 15.6, 5.2 Hz, 2H), 3.43 (dd, J = 15.6, 6.4 Hz, 2H), 3.30-3.08 (m, 4H), 1.17 (s, 18H); C NMR
δ 5.89-5.70 (m, 2H), 5.40-5.15 (m, 4H), 3.79 (dd, J
13
(100 MHz, CDCl3): 134.3, 118.4, 57.9, 50.3, 47.3, 22.9 (3×CH3); HRMS M+Na found:
δ
371.1804. C16H32N2O2S2+Na requires 371.1803.
Typical Procedure for the 1, 4-Addition of Boronic Acids to Cyclic Enones: The ligand 1a
(0.0035 g, 0.01 mmol), [Rh(C2H4)2Cl]2 (0.0038 g, 0.01 mmol) and PhB(OH)2 (0.24 g, 2 mmol)
were dissolved in dry THF and stirred for 1 h at 60 °C. To this solution the α,β-unsaturated
carbonyl compound (0.1 mL, 1.00 mmol) and an aqueous solution of K3PO4 (0.33 mL of 1.5 M, 0.5
mmol) were added in sequence to the reaction mixture and was further stirred at 60 °C. After
completion of the reaction (TLC), it was evaporated in vacuo to give the crude residue which was
purified by silica gel column chromatography to yield the product 3-aryl alkenone. The procedure
described above is representative for the following compounds.
(R)-3-phenylcyclohexan-1-one (18): colorless oil; Yield 95%; er (R:S) 96:4. Enantiomeric ratio
was determined by chiral HPLC analysis (CHIRALCEL OD-H, 1.5% IPA in hexane, 0.5 mL/min,
254 nm UV detector). tR = 20.64 min for (R) and tR = 21.81min for (S); [α]D: +20.1 (c 0.58, CHCl3);
1H NMR (400 MHz, CDCl3):
(m, 4H), 2.18-1.96 (m, 2H), 1.92-1.69 (m, 2H); C NMR (100 MHz, CDCl3):
129.4, 128.5, 126.4 , 48.7, 44.6 , 41.0, 32.5 , 25.4.
δ 7.42-7.28 (m, 2H), 7.28-7.13 (m, 3H), 3.05-2.92 (m, 1H), 2.63-2.28
13
δ 211.4, 144.1,
(R)-3-(m-tolyl) cyclohexan-1-one (18a): colorless oil; Yield 93%; er (R:S) 95:5. Enantiomeric
ratio was determined by chiral HPLC analysis (CHIRALCEL OD-H, 5% IPA in hexane, 0.7
mL/min, 254 nm UV detector). tR = 7.45 min for (R) and tR = 8.44 min for (S); [α]D: +17.4 (c 0.55,
CHCl3); 1H NMR (400 MHz, CDCl3):
δ
7.31-7.15 (m, 1H), 7.07-6.97 (m, 3H), 3.09-2.86 (m, 1H),
2.66-2.36 (m, 4H), 2.34 (s, 3H), 2.20-2.02 (m, 2H), 1.90-1.68 (m, 2H); 13C NMR (100 MHz,
CDCl3): 211.1, 144.3, 138.2, 128.5, 127.4, 127.3, 123.5, 48.9, 44.4, 41.1, 32.8, 25.5, 21.4.
δ
(R)-3-(3-fluorophenyl) cyclohexan-1-one (18b): colorless oil; Yield 70%; er (R:S) 98:2
Enantiomeric ratio was determined by chiral HPLC analysis (CHIRALPAK AD-H, 5% IPA in
hexane, 0.8 mL/min, 254 nm UV detector). tR = 6.19 min for (R) and tR = 6.95min for (S); [α]D:
+15.8 (c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3):
δ
7.45-7.17 (m, 1H), 7.00 (d, J = 7.6 Hz, 1H),
6.97-6.85 (m, 2H), 3.14-2.92 (m, 1H), 2.72-2.27 (m, 4H), 2.24-1.98 (m, 2H), 1.97-1.67 (m, 2H);
13C NMR (100 MHz, CDCl3):
210.4, 162.9 (d, J = 244.4 Hz), 146.8 (d, J = 6.8 Hz), 130.1 (d, J =
δ
8.4 Hz), 122.2 (d, J = 2.8 Hz), 113.5 (d, J = 5.6 Hz), 113.3 (d, J = 5.8 Hz), 48. 6 (CH2), 44.3 (d, J =
1.6 Hz), 41.0, 32.5, 25.3.
(R)-3-(4-methoxyphenyl) cyclohexan-1-one (18c): White solid; Yield 93%; er (R:S) 96:4.
Enantiomeric ratio was determined by chiral HPLC analysis (CHIRALPAK AD-H, 2% IPA in
hexane, 0.3 mL/min, 254 nm UV detector). tR = 17.27 min for (R) and tR = 18.06 min for (S); [α]D:
+13.8 (c 0.99, CHCl3); 1H NMR (400 MHz, CDCl3):
δ
7.14 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz,
2H), 3.78 (s, 3H), 3.10-2.86 (m, 1H), 2.60-2.29 (m, 4H), 2.21-1.96 (m, 2H), 1.93-1.67 (m, 2H); 13C
NMR (100 MHz, CDCl3): 211.1, 158.1, 136.4, 127.3, 113.9, 55.1, 49.1, 43.8, 41.0, 32.9, 25.3.
δ
(R)-3-phenylcyclopentan-1-one (22a): colorless oil; Yield 95%; er (R:S) 99:1 Enantiomeric ratio
was determined by chiral HPLC analysis (CHIRALPAK AD-H, 0.2% IPA in hexane, 0.5 mL/min,
254 nm UV detector). tR = 39.60 min for (R) and tR = 43.98 min for (S); [α]D: +86.1 (c 0.65,
CHCl3); 1H NMR (400 MHz, CDCl3):
2.63 (dd, J = 18.2, 7.6 Hz, 1H), 2.53-2.20 (m, 4H), 2.05-1.84 (m, 1H); C NMR (100 MHz,
δ 7.42-7.30 (m, 2H), 7.29-7.20 (m, 3H), 3.52-3.30 (m, 1H),
13
CDCl3):
δ
218.1, 142.9, 128.4, 126.52, 126.49, 45.5, 42.0, 38.6, 31.0.
12

ACCEPTED MANUSCRIPT
(R)-3-(4-methoxyphenyl) cyclopentan-1-one (22b): colorless oil; Yield 99%; er (R:S) 94:6
Enantiomeric ratio was determined by chiral HPLC analysis (CHIRALCEL OD-H, 1% IPA in
hexane, 0.5 mL/min, 254 nm UV detector). tR = 34.82 min for (R) and tR = 40.99 min for (S); [α]D:
+72.5 (c 0.04, CHCl3); 1H NMR (400 MHz, CDCl3):
δ 7.18 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz,
2H), 3.80 (s, 3H), 3.48-3.27 (m, 1H), 2.64 (dd, J = 18.2, 7.4 Hz, 1H), 2.58-2.18 (m, 4H), 2.01-1.88
(m, 1H); 13C NMR (100 MHz, CDCl3):
31.3.
δ 218.6, 158.3, 135.0, 127.6, 114.0, 55.2, 46.0, 41.4, 38.8,
(R)-3-(4-(tert-butyl) phenyl) cyclopentan-1-one (22c): colorless oil; Yield 81%; er (R:S) 86:14
Enantiomeric ratio was determined by chiral HPLC analysis (CHIRALCEL OD-H, 2% IPA in
hexane, 0.5 mL/min, 254 nm UV detector). tR = 9.15 min for (R) and tR = 10.15 min for (S); [α]D:
+49.1 (c 0.11, CHCl3); 1H NMR (400 MHz, CDCl3):
δ
7.37 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz,
2H), 3.55-3.26 (m, 1H), 2.66 (dd, J = 18.2, 7.4 Hz, 1H), 2.58-2.22 (m, 4H), 2.10-1.87 (m, 1H), 1.32
13
(s, 9H); C NMR (100 MHz, CDCl3):
δ 218.7, 149.6, 139.9, 126.4, 125.5, 45.8, 41.7, 38.9, 34.4,
31.3 (3×CH3), 31.2.
Acknowledgements: O. R. thanks the Council of Scientific and Industrial Research (CSIR), New
Delhi for a research fellowship. M. B. U. thanks Indian Institute of Science, Bangalore for a
fellowship.
References
#Abstracted from the PhD thesis of Omkar Revu submitted to the Indian Institute of Science
1. Rhodium and Palladium Catalyzed Asymmetric Conjugate Additions. Berthon, G.; Hayashi, T. in
Catalytic Asymmetric Conjugate Reactions. Cordova, A. (Ed). Wiley-VCH, Weinheim. 2010.
Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829-2844.
2. For a review on Rh-catalyzed conjugate addition reactions see: P. Tian, H.-Q. Dong and G.-Q.
Lin, ACS Catal., 2012, 2, 95.
3. For an excellent review on chiral sulfur-olefin liagnds in Rh-catalyzed asymmetric conjugate
addition reactions see: Li, Y.; Xu, M. –H. Chem. Commun., 2014, 50, 3771 and references cited
therein.
4. Allylation of sulfinimines using indium/ allylbromdie see: (a) Gonzalez-Gomez, J. C.; Medjahdi,
M. Foubelo, F.; Yus, M. J. Org. Chem. 2010, 75, 6308. (b) Bosque, I.; Gonzalez-Gomez, J. C.;
Foubelo, F.; Yus, M. J. Org. Chem. 2012, 77, 780. For a review on the use of t-butane sulfinamides
see: Robak, M. A. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev., 2010, 110 3600.
5. It was reported by Sun et. al. (Sun, X.; Wang, S.; Sun, S.; Zhu, J.; Deng, J. Synlett., 2005, 18,
2776) that the reaction of the bis-sulfinimine 5 with allylbromide and zinc led to the formation of
the sinlge diastereomer 1a. However, we were not able to reproduce the same in our hands and the
reaction always resulted in the formation of three diastereomers.
6. Crystal structure data has been deposited with the Cambridge Crystallographic Data Center
(CCDC). CCDC numbers for 1a: 1405612; 1c: 1058816.
7. Crystal structure data has been deposited with the Cambridge Crystallographic Data Center
(CCDC). CCDC number 1432175.
8. Further mechanistic studies to elucidate the mechanism are currently underway.
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Graphical abstract
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