Halodiazophosphonates, a New Class of Diazo Compounds for the Diastereoselective Intermolecular Rh(II) Catalyzed Cyclopropanation

Abstract

(Halodiazomethyl)phosphonates 2A-C have been generated by a one-pot procedure via a clean, efficient, and rapid deprotonation/electrophilic halogenation sequence from diethyl diazomethylphosphonate 1 (EDP). Subsequent intermolecular Rh(II)-catalyzed cyclopropanation afforded the corresponding halocyclopropylphosphonates 3-10 in moderate to high yields and high diastereomeric ratios. Catalyst loadings down to 0.1 mol % as well as clean and selective product formation were achieved.

Pd‐initiated polymerization of diazo compounds bearing dialkoxyphosphinyl group and hydrolysis of the resulting polymers and oligomers to afford phosphonic acid‐containing products

“…π‐AllylPdCl ( 3 ) (Strem Chem, 99%), NaBPh 4 ( 4 ) (Kanto Chemical, >99.5%), bromoacetyl bromide (TCI, >98%), 1,8‐diazabicyclo[5.4.0]‐7‐undecene (DBU: Nacalai Tesque, 97%), and trimethylsilyl bromide (TMSBr, TCI, 98%) were used as received. N , N ’‐Ditosylhydrazine, benzyl diazoacetate (BDA 5 ), dialkyl (ethyl, n ‐butyl, and isopropyl) 2‐hydroxyethylphosphonates, and diethyl diazomethylphophonate ( 2 ) were prepared according to the literatures. Extra care must be taken for preparation and handling of the diazo compounds because of their potential explosiveness.…”

Enantiodivergent Synthesis of Halofuginone by Candida antarctica Lipase B (CAL-B)-Catalyzed Kinetic Resolution in Cyclopentyl Methyl Ether (CPME)

“…(2-Oxo-propyl)-phosphonic acid diethyl ester (10) 19 Chloroacetone (2 mL, 25 mmol) was added to a suspension of KI (4.6 g, 27.5 mmol) in anhydrous CH3CN (10 mL) and anhydrous acetone (10 mL) and the reaction was stirred at room temperature for 1 h. Then triethylphosphite (4.34 mL, 25 mmol) was added dropwise in 10 min. After 16 h, the reaction mixture was quenched with water (20 mL) and extracted with EtOAc (3 x 40 mL).…”

“…Scheme 1 Previous literature reports on EKR and the approach reported herein Thus, commercially available, N-Cbz-protected 1,2,3,4tetrahydropyridine 8 (Scheme 2) was treated with Oxone ® (2 equiv) in acetone/water and in the presence of K 2 CO 3 (2 equiv) to obtain hemiaminal 9 (96% yield) 18 that, as the crude product, was subjected to Horner-Wadsworth-Emmons (HWE) olefination by reaction with phosphonate 10 19 to give alcohol 11 with E geometry. 9 Treatment of crude 11 with BF 3 •Et 2 O in anhydrous acetonitrile eventually provided racemic 3a contaminated with furan derivative 12 (15% by 1 H NMR analysis).…”

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

“…Firstly, replacement of an electronegative oxygen atom with a non-polar methylene group may reduce affinity for the phosphate-recognizing-protein active site. 16 Thus, a-bromophosphonates may have different steric requirements than their uoro-derived counterparts. The phosphonate group may also exhibit changes in charge state, for example if the pK a of the phosphonic acid is increased above physiological pH; 10 this can make salt bridge or hydrogen bond contacts less favorable in an enzyme active site.…”