Catalytic Enantioselective Synthesis of N-C Axially Chiral N-(2,6-Disubstituted-phenyl)sulfonamides through Chiral Pd-Catalyzed N-Allylation

Recently, catalytic enantioselective syntheses of N-C axially chiral compounds have been reported by many groups. Most N-C axially chiral compounds prepared through a catalytic asymmetric reaction possess carboxamide or nitrogen-containing aromatic heterocycle skeletons. On the other hand, although N-C axially chiral sulfonamide derivatives are known, their catalytic enantioselective synthesis is relatively underexplored. We found that the reaction (Tsuji–Trost allylation) of allyl acetate with secondary sulfonamides bearing a 2-arylethynyl-6-methylphenyl group on the nitrogen atom proceeds with good enantioselectivity (up to 92% ee) in the presence of (S,S)-Trost ligand-(allyl-PdCl)2 catalyst, affording rotationally stable N-C axially chiral N-allylated sulfonamides. Furthermore, the absolute stereochemistry of the major enantiomer was determined by X-ray single crystal structural analysis and the origin of the enantioselectivity was considered.


Introduction
Atropisomers (N-C axially chiral compounds), owing to the rotational restriction around an N-C single bond, have recently attracted much attention [1][2][3][4][5][6][7]. In 2002 and 2005, we reported the enantioselective syntheses of ortho-tert-butyl anilides IA and IB through chiral Pd-catalyzed N-allylation (Tsuji-Trost allylation) and N-arylation (Buchwald-Hartwig amination), respectively (Scheme 1a) [8,9]. The N-allylation reaction shown in Scheme 1a was the first example of the catalytic asymmetric synthesis of N-C axially chiral compounds [8], although the enantioselectivity was by no means satisfactory. The enantioselectivity was significantly improved by using N-arylation instead of N-allylation, and N-arylated anilide products IB were obtained in 88-96% ee [9]. In 2010, as the first catalytic asymmetric synthesis of non-amide type N-C axially chiral compounds, we succeeded in the enantioselective construction of N-(ortho-tert-butylphenyl)-2-arylindoles II through chiral Pd(II)-catalyzed 5-endo-hydroaminocyclization of 2-alkynyl aniline derivatives (Scheme 1b) [10]. Since the publication of the reactions shown in Scheme 1a,b, N-C axially chiral compounds have been widely accepted as new target molecules for catalytic asymmetric reactions, and more than 130 original papers on their catalytic enantioselective syntheses have been published to date [2][3][4][5][6][7]. Most N-C axially chiral compounds, which have been prepared through catalytic asymmetric reactions, are carboxamide derivatives such as I or nitrogen-containing aromatic heterocycles such as II.
been prepared through catalytic asymmetric reactions, are carboxamide derivatives such as I or nitrogen-containing aromatic heterocycles such as II.

Scheme 1. Catalytic enantioselective synthesis of various N-C axially chiral compounds I-III.
On the other hand, although N-C axially chiral sulfonamides are also known [11][12][13][14], their catalytic asymmetric synthesis was not reported until recently. Since some N-C axially chiral sulfonamides are pharmaceutically attractive compounds, their catalytic asymmetric synthesis is meaningful from the viewpoint of not only synthetic organic chemistry, but also medicinal chemistry. In 2019, we and Zhao et al. independently reported the catalytic asymmetric synthesis of N-C axially chiral sulfonamides IIIA and IIIB through N-allylation with a chiral Pd catalyst and a chiral organic base, respectively (Scheme 1c,d) [15,16]. The products in Scheme 1c (our reaction) were N-(ortho-mono-tert-butylphenyl)sulfonamides IIIA, which are rotationally somewhat unstable, while the products in Scheme 1d (Zhao's reaction) were N- (2,6-disubstituted-phenyl)sulfonamides IIIB, which are rotationally relatively stable. Subsequently, other groups also succeeded in the catalytic enantioselective synthesis of N- (ortho-mono-tert-butylphenyl) and N- (2,6-disubstituted-phenyl)sulfonamides through similar or other asymmetric reactions [17][18][19][20][21][22]. We were curious about whether our method via chiral Pd-catalyzed N-allylation can also be applied to the enantioselective synthesis of N- (2,6-disubstituted-phenyl)sulfonamides.
In this article, we report the catalytic enantioselective synthesis of N-C axially chiral N- (2,6-disubstituted-phenyl)sulfonamides through the chiral Pd-catalyzed N-allylation of secondary sulfonamides (Scheme 2). It was found that N-allylation with N- (2-arylethynyl-6-methylphenyl)sulfonamides proceeded with good enantioselectivity in the presence of (S,S)-Trost ligand-(allyl-PdCl)2 to give rotationally stable N-C axially chiral sulfonamides in a reasonable yield. Furthermore, the absolute stereochemistry of the major enantiomer was determined and the origin of the enantioselectivity was rationally explained. Scheme 2. Catalytic enantioselective synthesis of N-C axially chiral N- (2,6-disubstituted-phenyl)sulfonamides 2 though chiral Pd-catalyzed N-allylation.

Scheme 1. Catalytic enantioselective synthesis of various N-C axially chiral compounds I-III.
On the other hand, although N-C axially chiral sulfonamides are also known [11][12][13][14], their catalytic asymmetric synthesis was not reported until recently. Since some N-C axially chiral sulfonamides are pharmaceutically attractive compounds, their catalytic asymmetric synthesis is meaningful from the viewpoint of not only synthetic organic chemistry, but also medicinal chemistry. In 2019, we and Zhao et al. independently reported the catalytic asymmetric synthesis of N-C axially chiral sulfonamides IIIA and IIIB through N-allylation with a chiral Pd catalyst and a chiral organic base, respectively (Scheme 1c,d) [15,16]. The products in Scheme 1c (our reaction) were N-(ortho-monotert-butylphenyl)sulfonamides IIIA, which are rotationally somewhat unstable, while the products in Scheme 1d (Zhao's reaction) were N- (2,6-disubstituted-phenyl)sulfonamides IIIB, which are rotationally relatively stable. Subsequently, other groups also succeeded in the catalytic enantioselective synthesis of N-(ortho-mono-tert-butylphenyl) and N- (2,6disubstituted-phenyl)sulfonamides through similar or other asymmetric reactions [17][18][19][20][21][22]. We were curious about whether our method via chiral Pd-catalyzed N-allylation can also be applied to the enantioselective synthesis of N- (2,6-disubstituted-phenyl)sulfonamides.
In this article, we report the catalytic enantioselective synthesis of N-C axially chiral N- (2,6-disubstituted-phenyl)sulfonamides through the chiral Pd-catalyzed N-allylation of secondary sulfonamides (Scheme 2). It was found that N-allylation with N- (2-arylethynyl-6-methylphenyl)sulfonamides proceeded with good enantioselectivity in the presence of (S,S)-Trost ligand-(allyl-PdCl) 2 to give rotationally stable N-C axially chiral sulfonamides in a reasonable yield. Furthermore, the absolute stereochemistry of the major enantiomer was determined and the origin of the enantioselectivity was rationally explained. On the other hand, although N-C axially chiral sulfonamides are also known [11][12][13][14], their catalytic asymmetric synthesis was not reported until recently. Since some N-C axially chiral sulfonamides are pharmaceutically attractive compounds, their catalytic asymmetric synthesis is meaningful from the viewpoint of not only synthetic organic chemistry, but also medicinal chemistry. In 2019, we and Zhao et al. independently reported the catalytic asymmetric synthesis of N-C axially chiral sulfonamides IIIA and IIIB through N-allylation with a chiral Pd catalyst and a chiral organic base, respectively (Scheme 1c,d) [15,16]. The products in Scheme 1c (our reaction) were N-(ortho-mono-tert-butylphenyl)sulfonamides IIIA, which are rotationally somewhat unstable, while the products in Scheme 1d (Zhao's reaction) were N- (2,6-disubstituted-phenyl)sulfonamides IIIB, which are rotationally relatively stable. Subsequently, other groups also succeeded in the catalytic enantioselective synthesis of N- (ortho-mono-tert-butylphenyl) and N- (2,6-disubstituted-phenyl)sulfonamides through similar or other asymmetric reactions [17][18][19][20][21][22]. We were curious about whether our method via chiral Pd-catalyzed N-allylation can also be applied to the enantioselective synthesis of N- (2,6-disubstituted-phenyl)sulfonamides.
In this article, we report the catalytic enantioselective synthesis of N-C axially chiral N- (2,6-disubstituted-phenyl)sulfonamides through the chiral Pd-catalyzed N-allylation of secondary sulfonamides (Scheme 2). It was found that N-allylation with N- (2-arylethynyl-6-methylphenyl)sulfonamides proceeded with good enantioselectivity in the presence of (S,S)-Trost ligand-(allyl-PdCl)2 to give rotationally stable N-C axially chiral sulfonamides in a reasonable yield. Furthermore, the absolute stereochemistry of the major enantiomer was determined and the origin of the enantioselectivity was rationally explained.

Survey of Alkynyl Substituents
Subsequently, under the same conditions, alkynyl substituents of N- (2-ethynyl-6methylphenyl)-4-toluenesulfonylamide substrate, which gave the best result in Table 1, were explored (Table 2). Similar to 4-tolylethynyl derivative 1i, the reaction with (4-methoxylphenyl)ethynyl and phenylethynyl derivatives 1j and 1k also gave N-allylated products 2j and 2k with high yields (98 and 92%) and good enantioselectivities (88 and 89% ee, Entries 2 and 3). On the other hand, in the reaction with trimethylsilylethynyl and hexynyl derivatives 1l and 1m, a considerable decrease in the enantioselectivity was observed. In these cases, the products 2l and 2m were obtained in 75 and 77% ee, respectively (Entries 4 and 5).

Survey of Sulfonyl Substituents
The substituent effect on the sulfonyl group was further explored by using N-(2arylethynyl-6-methylphenyl)sulfonamide substrates (Table 3). Table 3. Substituent effect on sulfonyl group in enantioselective N-allylation. tive 1i, a maximum enantioselectivity (86% ee) was observed (Entry 9). Attempts w made to improve the enantioselectivity using other Trost ligands possessing a cyclohe skeleton. However, a decrease in the enantioselectivity or chemical yield was observ (Entries 10 and 11).

Survey of Alkynyl Substituents
Subsequently, under the same conditions, alkynyl substituents of N-(2-ethynyl methylphenyl)-4-toluenesulfonylamide substrate, which gave the best result in Table  were explored (Table 2). Similar to 4-tolylethynyl derivative 1i, the reaction with (4-me oxylphenyl)ethynyl and phenylethynyl derivatives 1j and 1k also gave N-allylated pro ucts 2j and 2k with high yields (98 and 92%) and good enantioselectivities (88 and 89% Entries 2 and 3). On the other hand, in the reaction with trimethylsilylethynyl and hexyn derivatives 1l and 1m, a considerable decrease in the enantioselectivity was observed. these cases, the products 2l and 2m were obtained in 75 and 77% ee, respectively (Entr 4 and 5).

Survey of Sulfonyl Substituents
The substituent effect on the sulfonyl group was further explored by using N-(2ylethynyl-6-methylphenyl)sulfonamide substrates (Table 3). The present reactions proceeded smoothly regardless of the electronic effect of the para-substituent on the benzenesulfonyl group, affording N-allylation products 2n-q with high yields (88%-quant) and good enantioselectivities (85-92% ee, Entries 2-5). With benzenesulfonyl amides 1o,p bearing an electron-withdrawing substituent such as a nitro group, a slight increase in enantioselectivity was observed (89 and 92% ee, Entries 3 and 4). The reaction of methanesulfonyl amides 1r also gave the product 2r with a good enantioselectivity (87% ee, Entry 6). On the other hand, in the reaction with bulky 2,4,6trimethylphenylsulfone amide 1s, the enantioselectivity was considerably lowered (63% ee, Entry 7).

Absolute Stereochemistry and Origin of Enantioselectivity
The absolute stereochemistry of the major enantiomer was determined to be (P)configuration by X-ray single crystal structural analysis of 2o ( Figure 1) with the flack parameter 0.02 (6) [33,34]. Although the absolute stereochemistries of other ortho-ethynyl sulfonamides 2f-s were not determined exactly, the major enantiomers of 2f-s (+61. 5-196.7 • ), which have large positive [α] D values such as 2o (+201 • ), were also predicted to possess the (P)-configuration (only methanesulfonamide 2r showed a small positive [α] D value = +7.7 • ). Moreover, in the previously reported reaction of N-(ortho-mono-tertbutylphenyl)sulfonamides using (S,S)-Trost ligand (Scheme 1c), since the N-allylated products IIIA possessing (P)-configuration were obtained as the major enantiomer, the ethynyl group is expected to act as a bulky substituent in a similar way to the tert-butyl group.
zenesulfonyl amides 1o,p bearing an electron-withdrawing substitu group, a slight increase in enantioselectivity was observed (89 and 9 4). The reaction of methanesulfonyl amides 1r also gave the product 2 tioselectivity (87% ee, Entry 6). On the other hand, in the reaction wit thylphenylsulfone amide 1s, the enantioselectivity was considerably l try 7).

Absolute Stereochemistry and Origin of Enantioselectivity
The absolute stereochemistry of the major enantiomer was deter figuration by X-ray single crystal structural analysis of 2o ( Figure 1) w eter 0.02 (6) [33,34]. Although the absolute stereochemistries of other o amides 2f-s were not determined exactly, the major enantiomers of which have large positive [α]D values such as 2o (+201 °), were also the (P)-configuration (only methanesulfonamide 2r showed a small p +7.7 °). Moreover, in the previously reported reaction of Ntylphenyl)sulfonamides using (S,S)-Trost ligand (Scheme 1c), since t ucts IIIA possessing (P)-configuration were obtained as the major ena group is expected to act as a bulky substituent in a similar way to the The (P)-selectivity in the present reaction may be rationalized on ing model proposed by Trost ( Figure 2) [35,36]. Among four possible A-D in the reaction with (S,S)-Trost ligand, TS-B and TS-C should be bilized because of the strong steric repulsion between the ortho-ethy group and Ph (wall) group (green color) on the phosphorus atom. TS favorable, due to the steric repulsion between the ortho-ethynyl group (blue color). As a result, the reaction preferentially proceeds via TS-A a major enantiomer. In other 2,6-disubstituted phenyl derivatives 1 ethynyl derivatives, the reaction may proceed via TS-D as well as T decrease in the enantioselectivity. Since a linear ortho-arylethynyl gro considerable steric interaction with Ph (wall) groups (blue color) on D, the reaction via TS-D may be disfavored, resulting in a good ena a substrate 1s bearing a bulky sulfonyl group (R 1 = 2,4,, t TS-A may be caused by the steric repulsion between the Ph (wall) gro and R 1 substituent, leading to the decrease in the enantioselectivity (T The (P)-selectivity in the present reaction may be rationalized on the basis of a working model proposed by Trost ( Figure 2) [35,36]. Among four possible transition states TS-A-D in the reaction with (S,S)-Trost ligand, TS-B and TS-C should be significantly destabilized because of the strong steric repulsion between the ortho-ethynyl or ortho-methyl group and Ph (wall) group (green color) on the phosphorus atom. TS-D may also not be favorable, due to the steric repulsion between the ortho-ethynyl group and Ph (wall) group (blue color). As a result, the reaction preferentially proceeds via TS-A, leading to (P)-2 as a major enantiomer. In other 2,6-disubstituted phenyl derivatives 1a-e except for ortho-ethynyl derivatives, the reaction may proceed via TS-D as well as TS-A, resulting in the decrease in the enantioselectivity. Since a linear ortho-arylethynyl group brings about the considerable steric interaction with Ph (wall) groups (blue color) on the back side in TS-D, the reaction via TS-D may be disfavored, resulting in a good enantioselectivity. With a substrate 1s bearing a bulky sulfonyl group (R 1 = 2,4,6-Me 3 C 4 H 2 ), the destabilization in TS-A may be caused by the steric repulsion between the Ph (wall) group on the front side and R 1 substituent, leading to the decrease in the enantioselectivity (

Rotational Stability of Sulfonamide Products
The rotational barriers of N-(ortho-mono-tert-butylphenyl)sulfonamide derivatives IIIAr and IIIAs, which were previously reported, were 25.2 and 25.5 kcal mol −1 at 298 K, respectively (Figure 3), and the ee of IIIAr and IIIAs decreased gradually at rt in CCl4 (t1/2 at 298K = 1.9 and 3.6 days). On the other hand, in N- (2-arylethynyl-6-methylphenyl)sulfonamide products 2r and 2i, the decrease in the ee was not observed even after standing for a few days at rt in CCl4. The barrier values of 2r and 2i were evaluated to be 28.3 and 28.7 kcal mol −1 at 333 K, which are ca. 3 kcal mol −1 higher than those of IIIAr and IIIAs. In N-allyl-N- (2-(4-tolyl)ethynyl)phenyl sulfonamide 3 bearing no methyl group at the other ortho-position, the enantiomers could not be separated through a chiral HPLC method because of the rotationally unstable structure. Indeed, two allylic hydrogens (Ha and Hb) in III and 2 were detected as nonequivalent signals in the 1 H NMR, while those in 3 showed an equivalent NMR signal, which suggests the quick rotation around the N-Ar bond at the NMR time scale. (Supplementary Materials)

Application to Enantioselective Double N-Allylation
Since N-allyl-N- (2,6-disubstituted-phenyl)sulfonamide products 2 were revealed to be rotationally stable at rt, we further investigated the enantioselective construction of two N-C chiral axes through a double N-allylation with bis-sulfonamide substrate (Scheme 3).

Rotational Stability of Sulfonamide Products
The rotational barriers of N-(ortho-mono-tert-butylphenyl)sulfonamide derivatives IIIAr and IIIAs, which were previously reported, were 25.2 and 25.5 kcal mol −1 at 298 K, respectively (Figure 3), and the ee of IIIAr and IIIAs decreased gradually at rt in CCl 4 (t 1/2 at 298K = 1.9 and 3.6 days). On the other hand, in N-(2-arylethynyl-6methylphenyl)sulfonamide products 2r and 2i, the decrease in the ee was not observed even after standing for a few days at rt in CCl 4 . The barrier values of 2r and 2i were evaluated to be 28.3 and 28.7 kcal mol −1 at 333 K, which are ca. 3 kcal mol −1 higher than those of IIIAr and IIIAs.

Rotational Stability of Sulfonamide Products
The rotational barriers of N-(ortho-mono-tert-butylphenyl)sulfonamide derivatives IIIAr and IIIAs, which were previously reported, were 25.2 and 25.5 kcal mol −1 at 298 K, respectively (Figure 3), and the ee of IIIAr and IIIAs decreased gradually at rt in CCl4 (t1/2 at 298K = 1.9 and 3.6 days). On the other hand, in N- (2-arylethynyl-6-methylphenyl)sulfonamide products 2r and 2i, the decrease in the ee was not observed even after standing for a few days at rt in CCl4. The barrier values of 2r and 2i were evaluated to be 28.3 and 28.7 kcal mol −1 at 333 K, which are ca. 3 kcal mol −1 higher than those of IIIAr and IIIAs. In N-allyl-N- (2-(4-tolyl)ethynyl)phenyl sulfonamide 3 bearing no methyl group at the other ortho-position, the enantiomers could not be separated through a chiral HPLC method because of the rotationally unstable structure. Indeed, two allylic hydrogens (Ha and Hb) in III and 2 were detected as nonequivalent signals in the 1 H NMR, while those in 3 showed an equivalent NMR signal, which suggests the quick rotation around the N-Ar bond at the NMR time scale. (Supplementary Materials)

Application to Enantioselective Double N-Allylation
Since N-allyl-N- (2,6-disubstituted-phenyl)sulfonamide products 2 were revealed to be rotationally stable at rt, we further investigated the enantioselective construction of two N-C chiral axes through a double N-allylation with bis-sulfonamide substrate (Scheme 3). In N-allyl-N-(2-(4-tolyl)ethynyl)phenyl sulfonamide 3 bearing no methyl group at the other ortho-position, the enantiomers could not be separated through a chiral HPLC method because of the rotationally unstable structure. Indeed, two allylic hydrogens (Ha and Hb) in III and 2 were detected as nonequivalent signals in the 1 H NMR, while those in 3 showed an equivalent NMR signal, which suggests the quick rotation around the N-Ar bond at the NMR time scale (Supplementary Materials).

Application to Enantioselective Double N-Allylation
Since N-allyl-N-(2,6-disubstituted-phenyl)sulfonamide products 2 were revealed to be rotationally stable at rt, we further investigated the enantioselective construction of two N-C chiral axes through a double N-allylation with bis-sulfonamide substrate (Scheme 3). In the presence of an achiral Pd catalyst, the double N-allylation with N-(2-bromo-6tolylethynylphenyl)bis-sulfonamide 4 proceeds smoothly to give a 1:1 mixture of diastereomeric double allylation products chiral-5 and meso-5 (82% yield). The stereochemistry of both diastereomers was determined by chiral HPLC method. That is, the HPLC of one diastereomer (chiral-5) using a CHIRALPAK AD-H column gave two peaks corresponding to enantiomers, while for the other diastereomer (meso-5), the enantiomer separation by chiral HPLC was not observed. No isomerization between chiral-5 and meso-5 was detected even after standing for a several days at rt. 22,27,x FOR PEER REVIEW 7 of 22 In the presence of an achiral Pd catalyst, the double N-allylation with N- (2-bromo-6-tolylethynylphenyl)bis-sulfonamide 4 proceeds smoothly to give a 1:1 mixture of diastereomeric double allylation products chiral-5 and meso-5 (82% yield). The stereochemistry of both diastereomers was determined by chiral HPLC method. That is, the HPLC of one diastereomer (chiral-5) using a CHIRALPAK AD-H column gave two peaks corresponding to enantiomers, while for the other diastereomer (meso-5), the enantiomer separation by chiral HPLC was not observed. No isomerization between chiral-5 and meso-5 was detected even after standing for a several days at rt. Subsequently, the enantioselective double N-allylation with 4 was conducted at −20 °C in the presence of (S,S)-Trost ligand-Pd catalyst. In this case, the double N-allylated products chiral-5 and meso-5 were obtained in a diastereomer ratio of 3.1:1 (88% yield). After the removal of meso-5 via MPLC separation, the optical purity of the obtained chiral-5 was found to be 99% ee. Since no the diastereoselectivity was observed at all under the achiral reaction conditions, it is obvious that the chiral axis constructed in the first N-allylation does not influence asymmetric induction in the second N-allylation (the stereoselectivity is only determined by the chiral catalyst).
The significantly high optical purity of double N-allylation product chiral-5 in comparison with mono-N-allylation products 2 (for example, 2g: 72% ee, Entry 7 in Table 1) can be rationally explained on the basis of the Horeau principle [37][38][39]. The product distributions (the enantiomeric excess and diastereomer ratio) in double asymmetric reactions are represented in Equations A and B (Scheme 4). When the ee (72% ee, x = 0.86) of 2-bromo-6-arylethynyl derivative 2g is used as the value (x) for the first asymmetric induction in Scheme 3, the ee of chiral-5 and the diastereomer ratio were calculated to be 95% and 3.2, respectively, which are similar to the experimental values (99% ee and dr = 3.1). Thus, it was revealed that bis-sulfonamide bearing two N-C chiral axes is obtained in a high optical purity through an asymmetric double N-allylation. Subsequently, the enantioselective double N-allylation with 4 was conducted at −20 • C in the presence of (S,S)-Trost ligand-Pd catalyst. In this case, the double N-allylated products chiral-5 and meso-5 were obtained in a diastereomer ratio of 3.1:1 (88% yield). After the removal of meso-5 via MPLC separation, the optical purity of the obtained chiral-5 was found to be 99% ee. Since no the diastereoselectivity was observed at all under the achiral reaction conditions, it is obvious that the chiral axis constructed in the first N-allylation does not influence asymmetric induction in the second N-allylation (the stereoselectivity is only determined by the chiral catalyst).
The significantly high optical purity of double N-allylation product chiral-5 in comparison with mono-N-allylation products 2 (for example, 2g: 72% ee, Entry 7 in Table 1) can be rationally explained on the basis of the Horeau principle [37][38][39]. The product distributions (the enantiomeric excess and diastereomer ratio) in double asymmetric reactions are represented in Equations A and B (Scheme 4). When the ee (72% ee, x = 0.86) of 2-bromo-6-arylethynyl derivative 2g is used as the value (x) for the first asymmetric induction in Scheme 3, the ee of chiral-5 and the diastereomer ratio were calculated to be 95% and 3.2, respectively, which are similar to the experimental values (99% ee and dr = 3.1). Thus, it was revealed that bis-sulfonamide bearing two N-C chiral axes is obtained in a high optical purity through an asymmetric double N-allylation.

General Information
Melting points were uncorrected. 1 H and 13 C NMR spectra were recorded on a 400 MHz spectrometer. In 1 H and 13 C NMR spectra, chemical shifts were expressed in δ (ppm) downfield from CHCl 3 (7.26 ppm) and CDCl 3 (77.0 ppm), respectively. HRMS were recorded on a double-focusing magnetic sector mass spectrometer using electron impact ionization. Column chromatography was performed on silica gel (75-150 μm). Medium-pressure liquid chromatography (MPLC) was performed on a 25 × 4 cm i.d. prepacked column (silica gel, 10 μm) with a UV detector. High-performance liquid chromatography (HPLC) was performed on a 25 × 0.4 cm i.d. chiral column with a UV detector. Optical rotations were measured in CHCl3 or MeOH on JASCO P-1020 Polarimeter at λ = 589 nm. [α]D values are reported at 25 °C in degree·cm 2 ·g -1 with concentrations reported in g/100 mL.

General Information
Melting points were uncorrected. 1 H and 13 C NMR spectra were recorded on a 400 MHz spectrometer. In 1 H and 13 C NMR spectra, chemical shifts were expressed in δ (ppm) downfield from CHCl 3 (7.26 ppm) and CDCl 3 (77.0 ppm), respectively. HRMS were recorded on a double-focusing magnetic sector mass spectrometer using electron impact ionization. Column chromatography was performed on silica gel (75-150 µm). Mediumpressure liquid chromatography (MPLC) was performed on a 25 × 4 cm i.d. prepacked column (silica gel, 10 µm) with a UV detector. High-performance liquid chromatography (HPLC) was performed on a 25 × 0.4 cm i.d. chiral column with a UV detector. Optical rotations were measured in CHCl 3 or MeOH on JASCO P-1020 Polarimeter at λ = 589 nm. [α] D values are reported at 25 • C in degree·cm 2 ·g -1 with concentrations reported in g/100 mL.

Conclusions
We found that the N-allylation of secondary sulfonamides bearing a 2-ethynyl-6methylphenyl group on the nitrogen atom proceeds with good enantioselectivity in the presence of (S,S)-Trost ligand-(allyl-PdCl) 2 catalyst, giving optically active N-C axially chiral N-allylated sulfonamides with good yields. The N-C axially chiral sulfonamide products were also revealed to possess relatively high rotational barriers and can be handled without a decrease in the ee at room temperature. Furthermore, the absolute stereochemistry of the major enantiomer was determined by X-ray single crystal structural analysis and the origin of the enantioselectivity was rationally explained on the basis of a working model by Trost. In addition, the double N-allylation with bis-sulfonamide substrate gave a N-allylated product with two N-C chiral axes in a high optical purity.