Lewis Acid‐Catalyzed Nucleophilic Substitutions of Benzylic Alcohols with Sulfamides

Abstract

Nucleophilic substitutions of benzylic alcohols with sulfamides were achieved using an FeCl 3 Lewis acid catalyst in MeNO 2 . It was necessary to adjust the reaction conditions to obtain efficient yields depending on the stability of the carbocation intermediates. The reaction could easily be performed, and it [a

Dehydrative amination of benzhydrols with electron-withdrawing group-substituted 2-aminopyridines utilizing Au(iii)/TPPMS catalyst system in water

“…However, no N -benzylated product 3a was formed when using amine 1a with ether 5 (Scheme 4B). 15 Next, we performed a competitive reaction using benzhydryl alcohol 2b and benzophenone ( 6 ) to exclude the possibility of the borrowing hydrogen pathway (Scheme 4C) 16 As expected, the direct substitution of alcohol 2b proceeded completely to give only the N -benzylated 3w in quantitative yield.…”

FeCl3‐Catalyzed Diastereodivergent Sulfamidation of Diarylmethanol Diastereomixtures Bearing a Chiral Auxiliary Dependent on Catalyst Loading

“…However, few examples using sulfamides as a nucleophile have been reported. In this context, we have recently developed an efficient method for producing benzylic sulfamides 3 that serves as an alternative method to those reported thus far; it comprises sulfamide 4 being applied to nucleophilic substitutions of benzylic alcohols 1 using an FeCl 3 [18,19] catalyst [Scheme 1, (b)] [20] . However, upon investigating the reaction mechanism, it was found that the reaction proceeded via carbocation intermediates, and the obtained products were racemates.…”

“…To further demonstrate the usability of this sulfamidation reaction, the sulfamide moieties on products 7 Aa and 7 Ba were deprotected to transform these compounds into their corresponding amines (Scheme 2). Referencing a previously reported literature procedure, [20,23] the single diastereomer of sulfamide 7 Aa was refluxed in 5% H 2 O‐pyridine for 24 h to afford the desired amine ( R,S )‐ 8 in quantitative yield with a dr of 99 : 1 [Scheme 2, (1)]. The absolute configuration of 8 was determined by comparing its analysis with that of the reported compound [21f] .…”

“…In this context, we have recently developed an efficient method for producing benzylic sulfamides 3 that serves as an alternative method to those reported thus far; it comprises sulfamide 4 being applied to nucleophilic substitutions of benzylic alcohols 1 using an FeCl 3 [18,19] catalyst [ Scheme 1,(b)]. [20] However, upon investigating the reaction mechanism, it was found that the reaction proceeded via carbocation intermediates, and the obtained products were racemates. Our research group has demonstrated the Lewis acid-catalyzed diastereoconvergent substitution of diastereomixtures of diarylmethanols 5 bearing chiral auxiliaries using various nucleophiles, such as 2-naphthols, [21a] allyltrimethylsilanes, [21b] benzamides, [21c] sodium sulfinates, [21d] 1,3-dicarbonyls, [21e] and sulfonamides, [21f] to produce the corresponding substituted products 6 [Scheme 1, (c)].…”

“…We first examined the reaction of diarylmethanol diastereomer 5 a [21] [diastereomeric ratio (dr) = ca. 60 : 40] with sulfamide 4 using previously established conditions [20] as shown in Table 1. When the reaction was carried out in MeNO 2 at 0 using 5 mol% of FeCl 3 as the catalyst, it was completed in 2 h and yielded 7 Aa in 91% yield with a dr of 97 : 3 (entry 1).…”