Preparation of Sulfamates and Sulfamides Using a Selective Sulfamoylation Agent

Abstract

Sulfamates and sulfamides are prevalent in biological molecules, but their universal synthetic methods are limited. We herein report a sulfamoylation agent with high solubility and shelf stability. Various sulfamates and sulfamides can be synthesized directly from alcohols or amines by employing this agent with high selectivity and high yields. This protocol was also successfully used for late-stage sulfamoylation of pharmaceuticals containing a hydroxyl or amino group.

Kukhtin–Ramirez-Reaction-Inspired Deprotection of Sulfamidates for the Synthesis of Amino Sugars

“…This significance has inspired tremendous efforts to devise elegant synthetic methods for the construction of amino alcohols [9][10][11][12][13][14][15]. Among them, the utility of sulfamate esters [16][17][18][19][20][21] as precursors of amino groups to form cyclic sulfamidate [22][23][24][25] via substitution [26,27], condensation [28][29][30], C-H amination [31][32][33][34], C-H aziridination [35], etc. [36][37][38], has been well established.…”

Catalyst-Controlled, Site-Selective Sulfamoylation of Carbohydrate Derivatives

“…The Burgess reagent ( 1a ) and related N -acylsulfene–Lewis base adducts engage with alcohols to generate N -acylsulfamates, which can either undergo further elimination, cyclization, or rearrangement reactions or serve as protected equivalents of primary sulfamates. Electrophiles that have been developed for the latter purpose include zwitterions 2a and 2b . Masked sulfamates can also be accessed using N -acylated sulfamoyl chlorides 3 , which are generated from alcohols and chlorosulfonyl isocyanate (ClSO 2 NCO).…”

Hexafluoroisopropyl Sulfamate: A Useful Reagent for the Synthesis of Sulfamates and Sulfamides

“…Its high sensitivity to hydrolysis also prevents long-term storage. Boc-protected Burgess-type salts 3a – 3c have been developed as sulfamoylation reagents with improved safety and stability, but Boc removal requires an additional step and strongly acidic conditions. , In 2020, the Miller laboratory disclosed a useful process employing pentachlorophenyl sulfamate (PCPS, 4 ) or pentafluorophenyl sulfamate (PFPS, 5 ) and catalytic NMI for the synthesis of sulfamates, with high selectivity for primary over secondary alcohols (e.g., N 6 -Bz-deoxyadenosine, 6a ) …”

“…The Burgess-type sulfamoylation reagents 3b and 3c and PCPS ( 4 ) are highly selective toward primary alcohols over secondary alcohols in diol or polyol substrates. , In order to probe the inherent selectivity of HFIPS toward primary and secondary alcohols, we designed a competition experiment involving alcohols 9a and 10a , which was followed by 1 H NMR (see Scheme ). Alcohols 9a and 10a were combined with HFIPS in equimolar amounts and stirred in CDCl 3 /pyridine- d 5 (7:3) or neat pyridine- d 5 at 30 °C.…”