Synlett 2019; 30(12): 1457-1461
DOI: 10.1055/s-0037-1611865
letter
© Georg Thieme Verlag Stuttgart · New York

High Stereocontrol in the Preparation of Silyl-Protected γ-Substituted Enoldiazoacetates

Kuiyong Dong
a  Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, United States   Email: michael.doyle@utsa.edu
b  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China   Email: xinfangxu@suda.edu.cn
,
a  Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, United States   Email: michael.doyle@utsa.edu
,
Xingfang Xu
b  Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. of China   Email: xinfangxu@suda.edu.cn
c  Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, P. R. of China
,
a  Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, United States   Email: michael.doyle@utsa.edu
› Author Affiliations
We acknowledge the U.S. National Science Foundation (CHE-1763168) for funding this research. The NMR spectrometer used in this research was supported by a grant from the U.S. National Science Foundation (CHE-1625963). K.D. acknowledges the support from China Scholarship Council (CSC).
Further Information

Publication History

Received: 14 April 2019

Accepted after revision: 28 May 2019

Publication Date:
26 June 2019 (eFirst)

Abstract

A robust and efficient synthesis of triisopropylsilyl (TIPS)-protected γ-substituted enoldiazoacetates with excellent Z stereocontrol by using lithium bis(trimethylsilyl)azanide (LiHMDS) as a base and TIPSOTf as a silyl transfer reagent is reported. Despite their increased size compared to previously tert-butyldimethylsilyl (TBS)-protected γ-unsubstituted enoldiazoacetates, a high product yield with exceptional stereocontrol has been achieved in copper-catalyzed [3+3] cycloaddition reaction with nitrones by using a chiral indeno bisoxazoline ligand.

Supporting Information

 
  • References and Notes


    • For reviews, see:
    • 1a Xu X, Doyle MP. Acc. Chem. Res. 2014; 47: 1396
    • 1b Deng Y, Cheng Q.-Q, Doyle MP. Synlett 2017; 28: 1695
    • 1c Cheng Q.-Q, Deng Y, Lankelma M, Doyle MP. Chem. Soc. Rev. 2017; 46: 5425
    • 1d Yin Z, He Y, Chiu P. Chem. Soc. Rev. 2018; 47: 8881
    • 1e Marichev KO, Doyle MP. Org. Biomol. Chem. 2019; 17: 4183

      For recent research articles, see:
    • 2a Li S.-J, Fang D.-C. Organometallics 2018; 37: 1373
    • 2b Marichev KO, Adly FG, Carranco AM, Garcia EC, Arman H, Doyle MP. ACS Catal. 2018; 8: 10392
    • 3a Deng Y, Massey LA, Zavalij P, Doyle MP. Angew. Chem. Int. Ed. 2017; 56: 7479
    • 3b Deng Y, Massey LA, Rodriguez Núñez YA, Arman H, Doyle MP. Angew. Chem. Int. Ed. 2017; 56: 12292
    • 3c Xu X, Zavalij PY, Hu W, Doyle MP. J. Org. Chem. 2013; 78: 1583
    • 3d Xu X, Zavalij PJ, Doyle MP. Chem. Commun. 2013; 49: 10287
    • 3e Qian Y, Xu X, Wang X, Zavalij PJ, Hu W, Doyle MP. Angew. Chem. Int. Ed. 2012; 51: 5900
    • 3f Xu X, Zavalij PJ, Doyle MP. Angew. Chem. Int. Ed. 2012; 51: 9829
    • 4a Shved AS, Tabolin AA, Novikov RA, Nelyubina YV, Timofeev VP, Ioffe SL. Eur. J. Org. Chem. 2016; 5569
    • 4b Zhu C, Xu G. Sun J. 2016; 55: 11867
    • 4c Nocquet P.-A, Opatz T. Eur. J. Org. Chem. 2016; 1156
    • 4d Xu X, Wang X, Zavalij PY, Doyle MP. Org. Lett. 2015; 17: 790
    • 5a Wang X, Zhou Y, Qiu L, Yao R, Zheng Y, Zhang C, Bao X, Xu X. Adv. Synth. Catal. 2016; 358: 1571
    • 5b Deng Y, Jing C, Doyle MP. Chem. Commun. 2015; 51: 12924
  • 7 Lienhard GE, Wang T.-C. J. Am. Chem. Soc. 1969; 91: 1146
    • 8a Ireland RE, Mueller RH, Willard AK. J. Am. Chem. Soc. 1976; 98: 2868
    • 8b Fataftah ZA, Kopka IE, Rathke MW. J. Am. Chem. Soc. 1980; 102: 3959
    • 8c Corey EJ, Gross AW. Tetrahedron Lett. 1984; 25: 495
  • 9 General Procedure for the Preparation of (Z)-Enoldiazoacetates 3: A 10 mL oven-dried vial equipped with a magnetic stirring bar was charged with diazoacetate 2 (0.50 mmol) and the system was filled with nitrogen. THF (2.0 mL) was then added, and the reaction solution was cooled to –78 °C (dry ice/acetone bath). LiHMDS (0.60 mL, 1.0 M in the hexanes) was introduced dropwise in 2 min, followed by the addition of TIPSOTf (168.5 mg, 0.55 mmol) at –78 °C. The resulting solution was stirred at –78 °C until the reaction was complete (monitored by TLC, about 5–15 min). THF was then removed under reduced pressure, and the residue was purified by column chromatography on silica gel which was pretreated with triethylamine (5 vol.%)/hexanes (eluent: pure hexanes) to give the desired products 3 in high yields and excellent stereoselectivity. Methyl (Z)-2-Diazo-3-[(triisopropylsilyl)oxy]hex-3-enoate (3a): Orange oil; Yield: 138 mg (88%). 1H NMR (500 MHz, CDCl3): δ = 5.07 (t, J = 7.2 Hz, 1 H), 3.80 (s, 3 H), 2.15–2.22 (comp, 2 H), 1.24–1.16 (comp, 3 H), 1.12 (d, J = 6.6 Hz, 18 H), 1.01 (t, J = 7.4 Hz, 3 H), 13C NMR (125 MHz, CDCl3): δ = 165.8, 133.4, 116.3, 52.1, 19.7, 18.0, 14.1, 13.5; HRMS (ESI): m/z [M + H]+ calcd for C16H31N2O3Si: 327.2098; found: 327.2093. Methyl (Z)-2-Diazo-3-[(triisopropylsilyl)oxy]pent-3-enoate (3b): Orange oil; Yield: 111 mg (71%). 1H NMR (500 MHz, CDCl3): δ = 5.13 (q, J = 7.0 Hz, 1 H), 3.77 (s, 3 H), 1.70 (d, J = 7.0 Hz, 3 H), 1.20–1.13 (comp, 3 H), 1.10 (d, J = 6.7 Hz, 18 H); 13C NMR (125 MHz, CDCl3): δ = 165.8, 134.7, 108.7, 52.1, 18.0, 13.5, 11.9; HRMS (ESI): m/z [M + H]+ calcd for C15H29N2O3Si: 313.1942; found: 313.1935. Methyl (Z)-2-Diazo-5-phenyl-3-[(triisopropylsilyl)oxy]pent-3-enoate (3c): Orange oil, Yield 165 mg (85%). 1H NMR (500 MHz, CDCl3): δ = 7.29 (t, J = 7.5 Hz, 2 H), 7.23 (d, J = 7.1 Hz, 2 H), 7.19 (t, J = 7.2 Hz, 1 H), 5.31 (t, J = 7.4 Hz, 1 H), 3.78 (s, 3 H), 3.54 (d, J = 7.4 Hz, 2 H), 1.26–1.18 (comp, 3 H), 1.13 (d, J = 6.9 Hz, 18 H); 13C NMR (125 MHz, CDCl3) δ = 165.6, 141.0, 134.6, 128.5, 128.5, 126.1, 112.6, 52.1, 32.5, 18.0, 13.5; HRMS (ESI): m/z [M + H]+ calcd for C21H33N2O3Si: 389.2255; found: 389.2251. For more examples, see the Supporting Information.
  • 10 Jing C, Cheng Q.-Q, Deng Y, Arman H, Doyle MP. Org. Lett. 2016; 18: 4550