Asymmetric Synthesis of α-Alkylated N-Sulfinyl Imidates as New Chiral Building Blocks

Abstract

Alpha-alkylation of N-sulfinyl imidates, prepared via condensation of tert-butanesulfinamide with ortho esters, led to alpha-substituted N-sulfinyl imidates in good-to-excellent diastereomeric ratios (dr up to >99:1) and yields. Deprotection of the alkylated N-sulfinyl imidates gave access to the corresponding imidate hydrochlorides in outstanding yields. These imidate hydrochlorides proved to be excellent intermediates for an easy transformation to chiral amides in good yields and enantiomeric excess upon simple heating in chloroform. Hydrolysis of the alpha-benzylated imidate hydrochlorides afforded the corresponding chiral esters with >95% ee.

Metal Free, Microwave Assisted Preparation of N-Sulfonyl and N-Sulfinyl Imines and Imidates

“…With two efficient methods for the synthesis of sulfonyl and sulfinyl imines from acetals, and being also interested in imidates, , we next considered applying similar conditions to the preparation of N -sulfonyl- and N -sulfinylimidates from orthoesters. N -Sulfonyl­imidates have mainly been used in diastereoselective α-alkylation reactions, ,, and can easily be converted into amides or esters, whereas N -sulfinylimidates have found applications in diastereoselective alkylations, Mannich-type condensations, conjugate additions, and diastereoselective aldol-type reactions . A few methods have been described for the preparation of such imidates, which suffer of long reaction time and tedious procedures.…”

Asymmetric Synthesis of δ‐Chloro‐β‐amino‐N‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines

“…The synthesis of the δ‐chloro‐ N ‐sulfinyl‐substituted imidate 8 was achieved by a modified literature procedure 17a,17b. Condensation of ( R S )‐ tert ‐butanesulfinamide ( 6 ) and orthoester 7 with a catalytic amount of p TsOH without solvent gave imidate ( R S )‐ 8 in high yield (Scheme ).…”

Total Synthesis of Lignan Lactone (–)-Hinokinin

“…We began our synthesis with the preparation of enantiopure ( R )- N - tert -butanesulfinyl imidate 14 (Scheme 2 ): treatment of the known nitrile 12 [ 49 , 50 ] with gaseous HCl in methanol yielded a good amount of trimethylorthoester intermediate [ 51 ], subsequent condensation of ( R )- tert -butanesulfinamide 13 and the corresponding trimethylorthoester with a catalytic amount of p -TsOH without solvent afforded chiral ( R )- N - tert -butanesulfinyl imidate 14 in 76 % overall yield [ 52 – 54 ]. With the N -sulfinyl imidate 14 in hand, we focused our attention on the construction of the pivotal butyrolactonimidate, as shown in Scheme 2 .…”