Synthesis of Stereoselectively Functionalized Silacyclopentanes

Dedicated to Professor Teruaki Mukaiyama in celebration of his 90^th birthday (Sotsuju)

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

An efficient approach to a variety of chiral silacyclopentanes having silicon stereogenic center based on the stereospecific transformations of C4 carbon stereogenic center of silacyclopentenols by ­Mitsunobu reaction or Tsuji–Trost reaction has been developed. The thus obtained substitution products can be converted into novel silacyclopentane triols, amines, and carboxylic acids in stereospecific manner.

Key words

asymmetric synthesis - chiral silicon molecule - silacyclopentanes - Mitsunobu reaction - Tsuji–Trost reaction

• References and Notes

• 1 Brook MA. Silicon in Organic, Organometallic, and Polymer Chemistry . John Wiley and Sons; New York: 2000
• 2 Bauer JO. Strohmann C. Eur. J. Inorg. Chem. 2016; 2868

Recent reports on stereoselective synthesis of chiral silicon molecules:
• 3a Bauer JO. Strohmann C. Angew. Chem. Int. Ed. 2014; 53: 720
• 3b Shintani R. Takagi C. Ito T. Naito M. Nozaki K. Angew. Chem. Int. Ed. 2015; 54: 1616
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• 3d Shintani R. Kurata H. Nozaki K. Chem. Commun. 2015; 51: 11378
• 3e Kumar R. Hoshimoto Y. Yabuki H. Ohashi M. Ogoshi S. J. Am. Chem. Soc. 2015; 137: 11838
• 3f Shintani R. Takano R. Nozaki K. Chem. Sci. 2016; 7: 1205
• 3g Zhang Q.-W. An K. Liu L.-C. Zhang Q. Guo H. He W. Angew. Chem. Int. Ed. 2017; 56: 1125
• 4a Igawa K. Takada J. Shimono T. Tomooka K. J. Am. Chem. Soc. 2008; 130: 16132
• 4b Igawa K. Yoshihiro D. Ichikawa N. Kokan N. Tomooka K. Angew. Chem. Int. Ed. 2012; 51: 12745
• 5a Nakazaki A. Nakai T. Tomooka K. Angew. Chem. Int. Ed. 2006; 45: 2235
• 5b Igawa K. Kokan N. Tomooka K. Angew. Chem. Int. Ed. 2010; 49: 728
• 6 Igawa K. Yoshihiro D. Abe Y. Tomooka K. Angew. Chem. Int. Ed. 2016; 55: 5814
• 7 Mitsunobu O. Synthesis 1981; 1
• 8 Selected Crystal Data for (S _Si*,4R*)-4a in Racemic Form Triclinic, P–1 (No. 2), a = 6.619(3) Å, b = 7.239(4) Å, c = 21.720(12) Å, α = 86.28(5)°, β = 84.55(4)°, γ = 73.97(3)°, V = 994.9(9) ų, Z = 2, R1 = 0.1460, wR2 = 0.1916, CCDC 1546493.
• 9 General Procedure for Mitsunobu Reaction of Silacyclopentenol 3 To a solution of (S _Si,4S)-3a (20.0 mg, 0.0860 mmol) in toluene (2 mL) was added PPh₃ (33.9 mg, 0.129 mmol), p-nitrobenzoic acid (17.3 mg, 0.104 mmol), and DEAD (58.7 μL of 2.20 M solution in toluene, 0.129 mmol) at rt and stirred for 6 h. The solvent of the reaction mixture was removed under reduced pressure. The crude product was purified by silica gel column chromatography (hexane/EtOAc = 50:1 to 30:1) to afford 27.5 mg (84%) of (S _Si,4R)-4a as a colorless crystal and 2.3 mg (12%) of 5 as a colorless oil, respectively. Compound Data of (S _Si,4R)-4a ¹H NMR (300 MHz, CDCl₃): δ = 8.32–8.21 (m, 4 H), 7.55–7.21 (m, 2 H), 7.41–7.34 (m, 3 H), 6.94 (dd, J = 10.2, 2.1 Hz, 1 H), 6.53 (dd, J = 10.2, 1.8 Hz, 1 H), 6.01–5.95 (m, 1 H), 1.85 (dd, J = 15.3, 8.1 Hz, 1 H), 1.14 (dd, J = 15.3, 5.7 Hz, 1 H), 1.02 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 164.4, 152.2, 150.6, 136.1, 134.9, 134.5, 131.9, 130.8, 129.5, 127.9, 123.6, 80.0, 26.9, 17.2, 14.6. IR (reflection): 2928, 1711, 1523, 1343, 1104, 901, 714, 638, 602, 520 cm^–1. HRMS (EI, positive): m/z calcd for C₁₇H₁₄NO₄Si [M – tBu]⁺, requires m/z: 324.0692; found: 324.0688. [α]_D ²⁶ –158.3 (c 1.02, CHCl₃) for >98% ee.

Silyl substituent effect on regioselective ring opening of epoxide, see:
• 10a Eisch JJ. Trainor JT. J. Org. Chem. 1963; 28: 2870
• 10b Manuel G. Boukherroub R. J. Organomet. Chem. 1993; 447: 167

Study on stereoselectivity of Tsuji–Trost reaction, see:
• 11a Hayashi T. Hagihara T. Konishi M. Kumada M. J. Am. Chem. Soc. 1983; 105: 7767
• 11b Murahashi S.-I. Taniguchi Y. Imada Y. Tanigawa Y. J. Org. Chem. 1989; 54: 3292
• 11c Granberg KL. Bäckvall J.-E. J. Am. Chem. Soc. 1992; 114: 6858
• 12 General Procedure for Tsuji–Trost Reaction of Methyl Carbonate 12 To a solution of dimethyl malonate (21.7 μL, 0.189 mmol) in THF (2 mL) was added NaH (63% in mineral oil, 7.2 mg, 0.189 mmol) at rt. After stirring for 20 min, to this solution was added P(o-tolyl)₃ (7.2 mg, 23.7 μmol), Pd₂(dba)₃·CHCl₃ (4.9 mg, 4.73 μmol), and a solution of carbonate (S _Si,4S)-12a (27.4 mg, 0.0943 mmol) in THF (1 mL) at that temperature, then stirred for 6.5 h at 50 °C. The reaction was quenched with sat. aq. NH₄Cl, then extracted with Et₂O. The combined organic phases were dried over Na₂SO₄, filtered, and the solvent was removed under reduced pressure. The crude product was purified by silica gel chromatography (hexane/Et₂O = 20:1) to afford 21.0 mg (64%) of (S _Si,4S)-13a as a colorless oil. IR (neat): 2953, 2855, 1738, 1435, 1200, 1142, 1008, 823, 730, 525 cm^–1. Compound Data of (S _Si,4S)-13a ¹H NMR (300 MHz, CDCl₃): δ = 7.51–7.48 (m, 2 H), 7.36–7.31 (m, 3 H), 6.81 (dd, J = 9.9, 1.8 Hz, 1 H), 6.30 (dd, J = 9.9, 2.4 Hz, 1 H), 3.65 (s, 3 H), 3.63 (s, 3 H), 3.54–3.44 (m, 1 H), 3.28 (d, J = 9.0 Hz, 1 H), 1.36 (dd, J = 15.3, 8.4 Hz, 1 H), 0.93 (s, 9 H), 0.71 (dd, J = 15.3, 6.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 169.0, 154.8, 136.5, 134.6, 129.1, 128.8, 127.7, 58.3, 52.4, 44.9, 26.7, 17.8, 10.6. HRMS (FAB, matrix: m-nitrobenzyl alcohol, positive): m/z calcd for C₁₅H₁₇O₄Si [M –tBu]⁺ requires 289.0896; found: 289.0897. [α]_D ²¹ +33.3 (c 0.20, CHCl₃) for >98% ee.