One and Two-Carbon Homologation of Primary and Secondary Alcohols to Corresponding Carboxylic Esters Using β-Carbonyl BT Sulfones as a Common Intermediate

Abstract

Herein we report the efficient one- and two-carbon homologation of 1° and 2° alcohols to their corresponding homologated esters via the Mitsunobu reaction using β-carbonyl benzothiazole (BT) sulfone intermediates. The one-carbon homologation approach uses standard Mitsunobu C-S bond formation, oxidation and subsequent alkylation, while the two-carbon homologation uses a less common C-C bond forming Mitsunobu reaction. In this latter case, the use of β-BT sulfone bearing esters lowers the p K sufficiently enough for the substrate to be used as a carbon-based nucleophile and deliver the homologated β-BT sulfone ester, and this superfluous sulfone group can then be cleaved. In this paper we describe several methods for the effective desulfonylation of BT sulfones and have developed methodology for one-pot alkylation-desulfonylation sequences. As such, overall, a one-carbon homologation sequence can be achieved in a two-pot (four step) procedure and the two-carbon homologation in a two-pot (three step) procedure (three-pot; four step when C-acid synthesis is included). This methodology has been applied to a wide variety of functionality (esters, silyl ethers, benzyls, heteroaryls, ketones, olefins and alkynes) and are all tolerated well providing good to very good overall yields. The power of our method was demonstrated in site-selective ingenol C20 allylic alcohol two-carbon homologation.

Unified Approach to Benzo[d]thiazol-2-yl-Sulfonamides

“…Finally, the BT-sulfonyl group removal was achieved using either a thiolate anion or NaBH 4 (Scheme 6C). 38…”

Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

“…2 1 H NMR (600 MHz, CDCl3) δ 7.34 (d, J = 7.8 Hz, 2H), 7.28 (t, J = 7.7 Hz, 2H), 7.18 (t, J = 7.3 Hz, 1H), 5.47 (dd, J = 12.2, 5.7 Hz, 1H), 5.38 (dt, J = 10.1, 7.4 Hz, 1H), 2.94 (t, J = 7.5 Hz, 2H), 2.38 (q, J = 7.4 Hz, 2H), 2.02 (p, J = 7.5 Hz, 2H), 0.96 (t, J = 7.6 Hz, 3H). 13 C NMR (150 MHz,CDCl3) δ 136.74,133.77,129.23,128.98,126.54,125.96,33.73,27.04,20.78,14.38. HRMS calcd.…”

“…1 H NMR (600 MHz, CDCl3) δ 7.65-7.46 (m, 5H), 5.51 (dt, J = 10.7, 7.1 Hz, 1H), 5.41-5.26 (m, 1H), 3.41 (t, J = 7.2 Hz, 2H), 2.58 (q, J = 7.3 Hz, 2H), 2.03 (p, J = 6.7, 6.3 Hz, 2H), 0.94 (t, J = 7.6 Hz, 3H). 13 C NMR (150 MHz,CDCl3) δ 154.27,134.80,133.66,130.00,129.69,125.08,123.77,33.19,26.67,20.62,14.07. HRMS calcd.…”

“…The title compound was prepared following a literature procedure. 14 To a flame-dried 10-mL roundbottom flask equipped with a stir bar was added (E)-2-((4-phenylbut-3-en-1-yl)sulfonyl)benzothiazole ( 9) (0.100 mmol, 1 equiv) in THF (1 mL, 0.1 M) and cooled to -78 ° C. LiHMDS (0.1 mL, 2.2 equiv; 1 M sol. in THF) was added followed quickly by ethyl carbonocyanidate (0.120 mmol, 1.2 equiv).…”

“…The title compound was prepared following a literature procedure. 14 To a 10-mL round-bottom flask equipped with a stirbar was added ethyl (E)-2-(benzothiazol-2-ylsulfonyl)-5-phenylpent-4-enoate (12-I) (0.100 mmol, 1 equiv) in THF (1 mL, 0.1 M). Zinc dust (0.500 mmol, 5 equiv) was added, and the reaction mixture was cooled to 0 ° C. AcOH (0.5 mL, excess) was added, and the reaction was allowed to warm to room temperature and stir for 8 h. EtOAc (10 mL) was added, and the crude mixture was filtered through a pad of Celite, which was washed with EtOAc.…”