Volume 3, Issue 5, Pages 834-845 (November 2017) Site-Divergent Delivery of Terminal Propargyls to Carbohydrates by Synergistic Catalysis  Ren-Zhe Li, Hua Tang, Liqiang Wan, Xia Zhang, Zhengyan Fu, Jie Liu, Shengyong Yang, Da Jia, Dawen Niu  Chem  Volume 3, Issue 5, Pages 834-845 (November 2017) DOI: 10.1016/j.chempr.2017.09.007 Copyright © 2017 Elsevier Inc. Terms and Conditions

Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Site-Divergent Propargylation of Carbohydrates: Prior Art, Reaction Design, and Potential Utility TES, triethylsilyl; PG, protecting group. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 2 Site-Divergent Propargylation of Various Monosaccharides Isolated yields of pure compounds were reported (0.25–1.0 mmol scale). Absolute stereochemical assignments were made by analogy to that of 26a or 28. Ratios (of the two products shown) were determined by 1H NMR analysis. In some cases, small amounts of other isomers were also formed. Product ratios resulting from the use of (±)-L4 are provided in the Supplemental Information. See Supplemental Information for experimental details. Dashed, double-headed arrows indicate diol moieties that could complex with B1. “All” denotes allyl. See Figures S24–S148 for 1D and 2D NMR spectra of the products in this figure. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 3 Site-Divergent Propargylation of a Non-protected Galactose Derivative Isolated yields are reported (0.5 mmol scale). See Supplemental Information for experimental details. Dashed, double-headed arrows indicate diol moieties that can complex with B1. See Figures S149–S158 for 1D and 2D NMR spectra of the products in this figure. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 4 Product Derivatization Reaction conditions: (i) CuI, air, Et3N/MeOH/THF, room temperature (rt); (ii) PdCl2(PPh3)2, CuI, methyl 4-iodobenzoate, Et3N, THF, rt; (iii) Ni(acac)2, PPh3, 4-MePhB(OH)2, Cs2CO3, 1,4-dioxane/MeOH, 90°C; (iv) IPrCuCl, KOtBu, (EtO)2SiMeH, tBuOH, toluene, rt; (v) Pd/C, H2 balloon, MeOH, rt; (vi) TsN3, CuI, Et3N, H2O, CHCl3, rt; (vii) PdCl2(PPh3)2, CuI, N-(2-iodophenyl)-tosylamide, dimethylformamide, 40°C. See Supplemental Information for experimental details. See Figures S159–S172 for 1H and 13C NMR spectra of the products in this figure. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 5 Propargylation of Natural Products Isolated yields were reported (0.05 mmol scale). Click conditions: CuSO4·5H2O, sodium ascorbate, organic azide, tBuOH/H2O, rt. Propargyl carbonate: 5-(4-benzoylphenoxy)pent-1-yn-3-yl tert-butyl carbonate. See Supplemental Information for experimental details. See also Figure S3. See Figures S173–S195 for 1D and 2D NMR spectra of the products in this figure. (A) Selective propargylation of cimiracemoside C. (B) Selective propargylation of digitoxin. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions

Scheme 1 Condition Optimization for the Propargylation of a Mannose Derivative 18 Yields were determined by 1H NMR analysis with 1,3,5-trimethylbenzene as internal standard unless otherwise noted. Ratios were determined by 1H NMR analysis of the crude reaction mixture. Small amounts of other isomers could also be observed. Entries 7, 8, 12, and 13: 4 Å molecular sieves were added; isolated yields. See Supplemental Information for experimental details. N.D., not determined. See Figures S4–S23 for 1D and 2D NMR spectra of the products in this scheme. Chem 2017 3, 834-845DOI: (10.1016/j.chempr.2017.09.007) Copyright © 2017 Elsevier Inc. Terms and Conditions