The Detosylation of Chiral 1,2-Bis(tosylamides)

Abstract

The deprotection of chiral 1,2-bis(tosylamides) to their corresponding 1,2-diamines is mostly unsuccessful under standard conditions. In a new methodology, the use of Mg/MeOH with sufficient steric additions allows the facile synthesis of 1,2-diamines in 78−98% yields. These results are rationalized using density functional theory and the examination of inner and outer-sphere reduction mechanisms.Note pubs.acs.org/joc

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran

“…The Dolby group reduced three substates to the corresponding Birch-type products in 45% to quantitative yield using lithium, ethylenediamine, n -propylamine, and t -butanol ( 4 ). This method was moderately successful in one instance ( 21 ) and was not effective in the N -detosylation of a challenging substrate ( 22 ). Donohoe and House reported the reduction of electron-deficient arenes and heterocycles using di- tert -butylbiphenyl ($1000/mol; Sigma-Aldrich) and lithium at −78°C (Fig.…”

“…More broadly, the structure-reactivity relationship indicates the potential for (reverse) chemoselective reduction in synthesis. To control the selectivity, inner- and outer-sphere electron transfer processes may be considered ( 22 , 24 ). Our work also suggests a broader role for the alcohol than previously considered, including the product selectivity with naphthalene and indole systems.…”

C(sp3)–H 1,3-diamination of cumene derivatives catalyzed by a dirhodium(ii) catalyst

“…Product 2aa can be reduced by LiAlH 4 to give monobenzenesulfonyl 13. In a solution of NaH, 13 was further reacted with iodomethane to produce the corresponding amine dimethylation product 14, and then by treatment with magnesium in methanol, [48][49][50] 1,3-diamine product 15 was successfully obtained (Scheme 4).…”

Improved Synthesis of the Amine Fragment of FR901464 and Thailanstatins through the Development of a Convenient N-Detosylation Method

“…Although alcohols are occasionally used to remove tosyl groups from amines under Birch reduction conditions, they are generally not required for the Birch reduction of electron-deficient arenes . A tosyl amide was also cleaved in the presence of lithium, n -propylamine, and ethylenediamine . However, the method was inefficient (30% yield), perhaps because neither THF nor t -butanol was used.…”

“…However, the method was inefficient (30% yield), perhaps because neither THF nor t -butanol was used. The underlying reason for our efficient detosylation method (and for reductive detosylation in general ,− ) is not yet understood, but the new method may find other applications in complex amine synthesis.…”