Catalytic Hydrosilylation of Carbonyl Compounds with Zinc(II) Acetate: Asymmetric Induction Collaborated with N₂S₂ Ligands

Abstract

Zinc acetate proved to be an efficient catalyst for hydro­silylation of ketones and aldehydes in the combination with (EtO)₂MeSiH, and a good to excellent asymmetric induction was observed in the presence of chiral N₂S₂ ligands.

Reduction method of carbonyl compounds has been rapidly progressing as compatible with social demands such as environmetally benign and inexpensive procedures. [¹] In this context, iron catalysts have been highlighted to show efficient activity including asymmetric induction with appropriate phosphine, nitrogen, or sulfur ligands. [²] In place of iron catalysts, biologically benign zinc-based catalyts can also be applied as one of alternatives. In 1999, actually, Mimoun et al. reported the excellent achievement of economical reduction method with zinc catalysts derived from Zn(2-ethylhexanoate)₂ (2-EH)/NaBH₄ or ZnEt₂/Me₂N(CH₂)₂NMe₂ (TMEDA) in the presence of inexpensive polymethylhydrosiloxane (PMHS) as a hydride donnor. [³] The zinc-catalyzed reduction of ketones was fol-lowed by Carpentier, [4] Parrodi-Juaristi-Walsh, [5] Mikami, [6] and Riant, [7] to disclose asymmetric reductions. Recently, Bandini-Umani-Ronchi [8] applied their chiral diamine-bisthiophene ligands with ZnEt₂ for asymmetric reduction of ketones. [9] Here, we disclose that Zn(OAc)₂ can act as an efficient catalyst for hydrosilylation of ketones with (EtO)₂MeSiH as hydride donor, and we show some examples for asymmetric induction by use of N₂S₂ ligands.

A system of Zn(2-EH)₂/PMHS reported by Mimoun needs NaBH₄ as a metal activator for hydrosilylation of ketones. [9] During our previous work for metal-catalyzed hydrosilylation, [¹0] we happened to find that a cheep zinc salt Zn(OAc)₂ by itself with (EtO)₂MeSiH sufficiently works a reducing agent of ketones. The representative example is as follows: methyl biphenyl-4-yl ketone (1) (1.0 mmol) was treated in a THF (3.0 mL) solution at 65 ˚C for 12 hours with Zn(OAc)₂ (0.05 mmol, 5 mol%) and (EtO)₂MeSiH (2.0 mmol). The hydrosilylation smoothly took place followed by hydrolysis to produce the corresponding secondary alcohol 2 in almost quantitative yield (Table  [¹] , entry 1). The reaction proceeded very slowly at 30 ˚C; ca. 50% for 72 hours (entry 2). The catalyst loading of 1 mol% worked sufficiently to result in the almost the same result (entry 3). The PMHS in place of (EtO)₂MeSiH did not work well under the above conditions, even in methanol-containing solution described by Mimoun ­(entry 4). Alkoxysilanes such as (EtO)Me₂SiH and (EtO)₃SiH gave good yields (entries 5 and 6), but alkyl­silanes did not give the product alcohol (entries 7 and 8).

Table 1 Catalytic Hydrosilylation of 1 with Zn(OAc)₂ and Hydrosilanes^a

Entry	Silane	Time (h)	Yield (%)
1	(EtO)2MeSiH	12	99
2b	(EtO)2MeSiH	72	49
3c	(EtO)2MeSiH	18	98
4	PMHS	24	trace
5	(EtO)Me2SiH	24	97
6	(EtO)3SiH	18	98
7	Et3SiH	24	no reaction
8	Me2PhSiH	24	no reaction
a Reaction conditions: 1 (1.0 mmol), silane (2.0 mmol), THF (3.0 mL). b At 30 ˚C. c With Zn(OAc)2 (1 mol%).

Under the conditions used in entry 1 of Table  [¹] , representative aromatic and aliphatic ketones were subjected to the hydrosilylation to give the corresponding secondary alcohols in high yields 91-99% (Table  [²] , entries 1-9). In addition, hydrosilylation of the several aldehydes was also demonstrated to give the corresponding primary alcohols in high yields 91-99% (entry 10-13). Benzalacetone was reduced to exclusively give 1,2-reduction product (entry 14).

In the case of reduction of ester groups, Mimoun reported that the reduction of methyl benzoate to benzyl alcohol was readily promoted by Zn(2-EH)₂/NaBH₄/PMHS system, while the reduction with Zn(OAc)₂/NaBH₄/PMHS resulted in a low yield 2%. [9] Therefore, we were interested in the reduction ability of our system with Zn(OAc)₂/(EtO)₂MeSiH using 4-MeOCOC₆H₄C(=O)Me (3) as a substrate (Scheme  [¹] ). Gratifyingly, the chemoselective hydrosilylation was realized at 50 ˚C on the ketone moiety to give the corresponding secondary alcohol 4 in 95 yield with small amount (ca. 5%) of the diol 5. Furthermore, both of the ketone and the ester moiety were reduced at 100 ˚C in a dioxane solution to the diol 5 in 72% with 24% of 4.

Table 2 Catalytic Hydrosilylation of Other Ketones and Aldehydes with Zn(OAc)₂ and (EtO)₂MeSiH^a

Entry	R¹	R²	Yield (%)
1	Ph	Me	98
2b	4-MeOC6H4	Me	98
3	4-BrC6H4	Me	98
4c	4-F3CC6H4	Me	91
5b	2,6-(MeO)2C6H3	Me	95
6	2-Naph	Me	98
7	Ph	n-C5H11	99
8	Ph(CH2)2	Me	99
9	n-C11H23	Me	99
10c	4-PhC6H4	H	99
11c	4-NCC6H4	H	91
12b,c	4-MeOPh	H	99
13c	9-Anth	H	93
14b	PhCH=CH	Me	99
a Reaction conditons: carbonyl compound (1.0 mmol), THF (3.0 mL), 12 h. b Work-up: KF (2 mmol), TBAF (TBAF, ca. 1 mL, 1 M in THF), 0 ˚C, 2 h. c 24 h.

Bandini-Umani-Ronchi have recently developed chiral diamino-bis(thiophene) ligands of N₂S₂ type, including 6a and 6b to apply them to asymmetric hydrosilylation of several ketones with ZnEt₂ and PMHS. [8] [¹¹] We were interested in study on the matching of Zn(OAc)₂ and the N₂S₂-type ligands 6a and 6b in asymmetric hydrosilylation. In addition, we newly prepared 4-subsituted thiophene ligands 7a and 7b for this purpose. The hydrosilylation in the presence of 6a and 6b proceeded smoothly at 30 ˚C to result in 61% and 63% ee of 2 (S), respectively (Table  [³] , entry 1 and 2). It is noteworthy that the ligands 7a and 7b with substituents at 4-position of the thiophene skeletons were capable to increase the enantioselectivity up to 78-83% (entry 3 and 4). It was thus found that modification on the thiophene rings could give us change of enantio­selectivity. The reaction with the ligand 7a was accelerated to finish at 65 ˚C for 3 hours, but the ee decreased to 50%.

Table 3 Asymmetric Hydrosilylation of 1 ^a

Entry	Ligand	Time (h)	Yield (%)	ee (%) (abs. config)
1	6a	24	99	61 (S)
2	6b	24	97	63 (S)
3	7a	24	98	83 (S)
4	7b	18	99	78 (S)
a Reaction conditons: 1 (1.0 mmol), 6 and 7 (6 mol%), THF (3.0 mL).

Some of ketone substrates (1.0 mmol) were examined for asymmetric hydrosilylation with Zn(OAc)₂ (5 mol%), (EtO)₂MeSiH (2 mmol), and N₂S₂ ligand 7a (6 mol%, Figure  [¹] ). Several substituted phenyl ketones were reduced in ca. 70% ee of 8-12. Methyl α-naphthyl ketone successfully gave the corresponding alcohol 13 in 92% ee (S) with 95% yield. [¹²] [¹³]

In conclusion, it was found that commercially available zinc acetate as a catalyst without any assistance of ligands could promote hydrosilylation of carbonyl compounds in the combination of diethoxymethylsilane. Although the asymmetric induction with chiral N₂S₂ ligands is still good to excellent, further experiments are now under way to reach high efficiency.

Acknowledgment

This work was partly supported by a Grant-in-Aid for Scientific ­Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Concerto Catalysts, 460:18065011), the Japan Society for the Promotion of Science (18350049).

References and Notes

• 1a Andersson PG. Munslow IJ. Modern Reduction Methods   Wiley-VCH; New York: 2008. 
• 1b Burke SD. Danheiser RL. Handbook of Reagents for Organic Synthesis, Oxidizing and Reducing Agents   John Wiley and Sons; Chichester: 1999. 
• For reviews, see:
• 2a Bullock RM. Angew. Chem. Int. Ed.  2007,  46:  7360 
  Search in Google Scholar
• 2b Enthaler S. Junge K. Beller M. Angew. Chem. Int. Ed.  2008,  47:  3317 
  Search in Google Scholar
• 2c Riant O. Mostefi N. Courmarcel J. Synthesis  2004,  2943 
• 2d For papers: Shaikh NS. Enthaler S. Junge K. Beller M. Angew. Chem. Int. Ed.  2008,  47:  2497 
  Search in Google Scholar
• 3a Mimoun H. J. Org. Chem.  1999,  64:  2582 
  Search in Google Scholar
• 3b Mimoun H. de Saint Laumer JY. Giannini K. Scopelliti R. Floriani C. J. Am. Chem. Soc.  1999,  121:  6158 
  Search in Google Scholar
• 4a Bette V. Mortrex A. Lehmann CW. Carpentier J.-F. Chem. Commun.  2003,  332 
• 4b Bette V. Mortorex A. Savoia D. Carpentier J.-F. Tetrahedron  2004,  60:  2837 
  Search in Google Scholar
• 5 Mastranzo VM. Quintero K. de Parrodi CA. Juaristi E. Walsh PJ. Tetrahedron  2004,  60:  1781 
  CrossrefSearch in Google Scholar
• 6 Ushio H. Mikami K. Tetrahedron Lett.  2005,  46:  2903 
  CrossrefSearch in Google Scholar
• 7 Gérard S. Pressel Y. Riant O. Tetrahedron: Asymmetry  2005,  16:  1889 
  CrossrefSearch in Google Scholar
• 8 Bandini M. Melucci M. Piccinelli F. Sinisi R. Tommasi S. Umani-Ronchi A. Chem. Commun.  2007,  4519 
  Crossref
• Hydrosilylation of imines with chiral zinc catalysts:
• 9a Ireland T. Fontanet F. Tchao G.-G. Tetrahedron Lett.  2004,  45:  4383 
  Search in Google Scholar
• 9b Park B.-M. Mun S. Yun J. Adv. Synth. Catal.  2006,  348:  1029 
  Search in Google Scholar
• 10a Nishiyama H. Furuta A. Chem. Commun.  2007,  760 
• 10b Furuta A. Nishiyama H. Tetrahedron Lett.  2008,  49:  110 
  Search in Google Scholar
• For compound 6, see:
• 11a Albano VG. Bandini M. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Adv. Synth. Catal.  2005,  347:  1507 
  Search in Google Scholar
• 11b Albano VG. Bandini M. Barbarella G. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Chem. Eur. J.  2006,  12:  667 
  Search in Google Scholar

Typical Procedure for Hydrosilylation of Methyl Biphenyl-4-yl Ketone (1) Zinc acetate (9.2 mg, 0.05 mmol; Wako 260-01881, lot LTM1219) and the ketone (196 mg, 1.0 mmol) were placed in a flask. Under an argon atmosphere, absolute THF (3.0 mL) was added at r.t. The mixture was stirred for 10 min at 65 ˚C, and (EtO)₂MeSiH (320 µL, 2.0 mmol) was then added by a syringe. The mixture was stirred for 24 h at 65 ˚C. The reaction was monitored by TLC examination; the ketone was consumed, and the silyl ether product was observed. At 0 ˚C, aq HCl (2 N, 2 mL) was added to quench the reaction. After stirring for 1 h, the mixture was extracted with EtOAc (3 × 10 mL), and the extract was washed with brine and aq NaHCO₃ and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography (hexane-EtOAc as eluent) to give the corresponding desired alcohol 2 (196 mg, 0.99 mmol) in 99%.
Asymmetric Hydrosilylation of Methyl α-Naphthyl Ketone
Under the same reaction conditions above described in the typical procedure, the ligand 7a (27.4 mg, 0.06 mmol) and methyl α-naphthyl ketone (170 mg, 1.0 mmol) were used to obtain the alcohol 13 (163 mg, 0.95 mmol) in 95% and 92% ee (S); analysis, CHIRALCEL OJ-H [hexane-2-PrOH (95:5), 0.8 mL min^-¹]; t _R (S) = 34.2 min, t _R (R) = 43.5 min.

Preparation of Ligands 7a and 7b
A mixture of (1R,2R)-cyclohexane-1,2-diamine (116 mg, 1.0 mmol), 4-phenylthiophene-2-carbaldehyde (392 g, 2.1 mmol, commercially available), MgSO₄ (2.4 g) in THF (10 mL) was stirred at r.t. for 40 h. After diluted with EtOAc (10 mL), the mixture was filtered through Celite and was concentrated to give white solids (ca. 470 mg). A MeOH solution (15 mL) of the solids was treated with NaBH₄ (392 mg) at r.t. for 18 h. Then, H₂O (15 mL) was added, and the mixture was extracted with EtOAc. The extract was washed with brine and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography with hexane-EtOAc to give white solids (265 mg, 0.58 mmol) in 58% yield.
Compound 7a: mp 113-115 ˚C. IR (KBr): ν = 3100, 3056, 2927, 2853, 1451, 737, 688 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 0.91-2.37 (m, 14 H), 3.90-3.94 (m, 2 H), 4.13-4.18 (m, 2 H), 7.24-7.39 (m, 8 H), 7.54-7.57 (m, 4 H). ^¹³C (75 MHz, CDCl₃): δ = 25.1, 31.6, 45.7, 60.4, 118.8, 123.4, 126.0, 126.7, 128.5, 135.8, 141.3, 145.7. Anal. Calcd (%) for C₂₈H₃₀N₂S₂: C, 73.32; H, 6.59; N, 6.11. Found: C, 72.91; H, 6.69; N, 6.01; [α]_D ^²9 -17.0 (c 1.00, CHCl₃).
Synthesis of Compound 7b
Starting from 2,6-diisopropylaniline via 2,6-diisopropyl-phenyliodide, 2,6-diisopropylphenyl boronic acid was prepared. The mixture of the boronic acid (463 mg, 2.25 mmol), 4-bromothiophene-2-carbaldehyde (318 mg, 1.5 mmol, commercially available), Pd(OAc)₂ (3.4 mg), S-Phos (12.7 mg), K₃PO₄ (650 mg, 3.0 mmol) in toluene (3.0 mL) at 100 ˚C for 24 h. The mixture was diluted with EtOAc and filtered through Celite. After concentration, the residue was purified by silica gel column chromatography to give
4-(2′,6′-diisopropylphenyl)thiophene-2-carbaldehyde (354 mg, 1.3 mmol) in 87%. A mixture of (1R,2R)-cyclohexane-1,2-diamine (46 mg, 0.4 mmol), thiophene-2-carbaldehyde (218 mg, 0.8 mmol, commercially available), and MgSO₄ (960 mg) in THF (5.0 mL) was stirred at r.t. for 24 h. After diluted with EtOAc, the mixture was filtered through Celite and was concentrated to give white solids. A MeOH solution (10 mL) of the solids was treated with NaBH₄ (151 mg) at r.t. for 24 h. Then, H₂O (10 mL) was added, and the mixture was extracted with EtOAc. The extract was washed with brine and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography with hexane-EtOAc to give the desired amine 7b (178 mg, 0.284 mmol) in 71% yield.
Compound 7b: oil. IR (film): ν = 3055, 2959, 2927, 2861, 1459, 751, 673 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.09-1.10 (m, 24 H), 1.15-1.40 (m, 6 H), 1.85 (m, 2 H), 2.23 (m, 2 H), 2.42 (m, 2 H), 2.83 (m, 4 H), 4.00 (d, J = 14.9 Hz, 2 H), 4.19 (d, J = 14.9 Hz, 2 H), 6.82 (s, 2 H), 6.93 (s, 2 H), 7.22-7.27 (m, 4 H), 7.38 (m, 2 H). ^¹³C (75 MHz, CDCl₃): δ = 24.2, 24.3, 24.5, 24.6, 25.1, 30.3, 30.4, 31.6, 45.5, 60.2, 121.0, 122.1, 126.9, 127.6, 134.4, 139.2, 144.0, 147.4. HRMS-FAB: m/z calcd for C₄₀H₅₅Cl₂N₂S₂ ⁺ [M + H]: 627.3807; found: 627.3805. [α]_D ^²9 -23.4 (c 1.00, CHCl₃).

References and Notes

• 1a Andersson PG. Munslow IJ. Modern Reduction Methods   Wiley-VCH; New York: 2008. 
• 1b Burke SD. Danheiser RL. Handbook of Reagents for Organic Synthesis, Oxidizing and Reducing Agents   John Wiley and Sons; Chichester: 1999. 
• For reviews, see:
• 2a Bullock RM. Angew. Chem. Int. Ed.  2007,  46:  7360 
  Search in Google Scholar
• 2b Enthaler S. Junge K. Beller M. Angew. Chem. Int. Ed.  2008,  47:  3317 
  Search in Google Scholar
• 2c Riant O. Mostefi N. Courmarcel J. Synthesis  2004,  2943 
• 2d For papers: Shaikh NS. Enthaler S. Junge K. Beller M. Angew. Chem. Int. Ed.  2008,  47:  2497 
  Search in Google Scholar
• 3a Mimoun H. J. Org. Chem.  1999,  64:  2582 
  Search in Google Scholar
• 3b Mimoun H. de Saint Laumer JY. Giannini K. Scopelliti R. Floriani C. J. Am. Chem. Soc.  1999,  121:  6158 
  Search in Google Scholar
• 4a Bette V. Mortrex A. Lehmann CW. Carpentier J.-F. Chem. Commun.  2003,  332 
• 4b Bette V. Mortorex A. Savoia D. Carpentier J.-F. Tetrahedron  2004,  60:  2837 
  Search in Google Scholar
• 5 Mastranzo VM. Quintero K. de Parrodi CA. Juaristi E. Walsh PJ. Tetrahedron  2004,  60:  1781 
  CrossrefSearch in Google Scholar
• 6 Ushio H. Mikami K. Tetrahedron Lett.  2005,  46:  2903 
  CrossrefSearch in Google Scholar
• 7 Gérard S. Pressel Y. Riant O. Tetrahedron: Asymmetry  2005,  16:  1889 
  CrossrefSearch in Google Scholar
• 8 Bandini M. Melucci M. Piccinelli F. Sinisi R. Tommasi S. Umani-Ronchi A. Chem. Commun.  2007,  4519 
  Crossref
• Hydrosilylation of imines with chiral zinc catalysts:
• 9a Ireland T. Fontanet F. Tchao G.-G. Tetrahedron Lett.  2004,  45:  4383 
  Search in Google Scholar
• 9b Park B.-M. Mun S. Yun J. Adv. Synth. Catal.  2006,  348:  1029 
  Search in Google Scholar
• 10a Nishiyama H. Furuta A. Chem. Commun.  2007,  760 
• 10b Furuta A. Nishiyama H. Tetrahedron Lett.  2008,  49:  110 
  Search in Google Scholar
• For compound 6, see:
• 11a Albano VG. Bandini M. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Adv. Synth. Catal.  2005,  347:  1507 
  Search in Google Scholar
• 11b Albano VG. Bandini M. Barbarella G. Melucci M. Monari M. Piccinelli F. Tommasi S. Umani-Ronchi A. Chem. Eur. J.  2006,  12:  667 
  Search in Google Scholar

Typical Procedure for Hydrosilylation of Methyl Biphenyl-4-yl Ketone (1) Zinc acetate (9.2 mg, 0.05 mmol; Wako 260-01881, lot LTM1219) and the ketone (196 mg, 1.0 mmol) were placed in a flask. Under an argon atmosphere, absolute THF (3.0 mL) was added at r.t. The mixture was stirred for 10 min at 65 ˚C, and (EtO)₂MeSiH (320 µL, 2.0 mmol) was then added by a syringe. The mixture was stirred for 24 h at 65 ˚C. The reaction was monitored by TLC examination; the ketone was consumed, and the silyl ether product was observed. At 0 ˚C, aq HCl (2 N, 2 mL) was added to quench the reaction. After stirring for 1 h, the mixture was extracted with EtOAc (3 × 10 mL), and the extract was washed with brine and aq NaHCO₃ and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography (hexane-EtOAc as eluent) to give the corresponding desired alcohol 2 (196 mg, 0.99 mmol) in 99%.
Asymmetric Hydrosilylation of Methyl α-Naphthyl Ketone
Under the same reaction conditions above described in the typical procedure, the ligand 7a (27.4 mg, 0.06 mmol) and methyl α-naphthyl ketone (170 mg, 1.0 mmol) were used to obtain the alcohol 13 (163 mg, 0.95 mmol) in 95% and 92% ee (S); analysis, CHIRALCEL OJ-H [hexane-2-PrOH (95:5), 0.8 mL min^-¹]; t _R (S) = 34.2 min, t _R (R) = 43.5 min.

Preparation of Ligands 7a and 7b
A mixture of (1R,2R)-cyclohexane-1,2-diamine (116 mg, 1.0 mmol), 4-phenylthiophene-2-carbaldehyde (392 g, 2.1 mmol, commercially available), MgSO₄ (2.4 g) in THF (10 mL) was stirred at r.t. for 40 h. After diluted with EtOAc (10 mL), the mixture was filtered through Celite and was concentrated to give white solids (ca. 470 mg). A MeOH solution (15 mL) of the solids was treated with NaBH₄ (392 mg) at r.t. for 18 h. Then, H₂O (15 mL) was added, and the mixture was extracted with EtOAc. The extract was washed with brine and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography with hexane-EtOAc to give white solids (265 mg, 0.58 mmol) in 58% yield.
Compound 7a: mp 113-115 ˚C. IR (KBr): ν = 3100, 3056, 2927, 2853, 1451, 737, 688 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 0.91-2.37 (m, 14 H), 3.90-3.94 (m, 2 H), 4.13-4.18 (m, 2 H), 7.24-7.39 (m, 8 H), 7.54-7.57 (m, 4 H). ^¹³C (75 MHz, CDCl₃): δ = 25.1, 31.6, 45.7, 60.4, 118.8, 123.4, 126.0, 126.7, 128.5, 135.8, 141.3, 145.7. Anal. Calcd (%) for C₂₈H₃₀N₂S₂: C, 73.32; H, 6.59; N, 6.11. Found: C, 72.91; H, 6.69; N, 6.01; [α]_D ^²9 -17.0 (c 1.00, CHCl₃).
Synthesis of Compound 7b
Starting from 2,6-diisopropylaniline via 2,6-diisopropyl-phenyliodide, 2,6-diisopropylphenyl boronic acid was prepared. The mixture of the boronic acid (463 mg, 2.25 mmol), 4-bromothiophene-2-carbaldehyde (318 mg, 1.5 mmol, commercially available), Pd(OAc)₂ (3.4 mg), S-Phos (12.7 mg), K₃PO₄ (650 mg, 3.0 mmol) in toluene (3.0 mL) at 100 ˚C for 24 h. The mixture was diluted with EtOAc and filtered through Celite. After concentration, the residue was purified by silica gel column chromatography to give
4-(2′,6′-diisopropylphenyl)thiophene-2-carbaldehyde (354 mg, 1.3 mmol) in 87%. A mixture of (1R,2R)-cyclohexane-1,2-diamine (46 mg, 0.4 mmol), thiophene-2-carbaldehyde (218 mg, 0.8 mmol, commercially available), and MgSO₄ (960 mg) in THF (5.0 mL) was stirred at r.t. for 24 h. After diluted with EtOAc, the mixture was filtered through Celite and was concentrated to give white solids. A MeOH solution (10 mL) of the solids was treated with NaBH₄ (151 mg) at r.t. for 24 h. Then, H₂O (10 mL) was added, and the mixture was extracted with EtOAc. The extract was washed with brine and dried over Na₂SO₄. After concentration, the residue was purified by silica gel column chromatography with hexane-EtOAc to give the desired amine 7b (178 mg, 0.284 mmol) in 71% yield.
Compound 7b: oil. IR (film): ν = 3055, 2959, 2927, 2861, 1459, 751, 673 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 1.09-1.10 (m, 24 H), 1.15-1.40 (m, 6 H), 1.85 (m, 2 H), 2.23 (m, 2 H), 2.42 (m, 2 H), 2.83 (m, 4 H), 4.00 (d, J = 14.9 Hz, 2 H), 4.19 (d, J = 14.9 Hz, 2 H), 6.82 (s, 2 H), 6.93 (s, 2 H), 7.22-7.27 (m, 4 H), 7.38 (m, 2 H). ^¹³C (75 MHz, CDCl₃): δ = 24.2, 24.3, 24.5, 24.6, 25.1, 30.3, 30.4, 31.6, 45.5, 60.2, 121.0, 122.1, 126.9, 127.6, 134.4, 139.2, 144.0, 147.4. HRMS-FAB: m/z calcd for C₄₀H₅₅Cl₂N₂S₂ ⁺ [M + H]: 627.3807; found: 627.3805. [α]_D ^²9 -23.4 (c 1.00, CHCl₃).