Asymmetric Synthesis of Cyclopropylamines Starting from N-Sulfinyl α-Chloro Ketimines

Abstract

Treatment of novel chiral N-sulfinyl alpha-chloro ketimines with Grignard reagents resulted in the synthesis of chiral N-(1-substituted cyclopropyl)-tert-butanesulfinamides in acceptable to good yields and diastereoselectivity via 1,3-dehydrohalogenation and subsequent addition of the Grignard reagent to the intermediate cyclopropylideneamine. Only in the case of allylmagnesium chloride did the reaction lead to aziridines in high yield. Further deprotection toward N-unprotected 1-substituted cyclopropylamines was established, and the absolute configuration was determined. [reaction: see text].

Synthesis and Applications of tert-Butanesulfinamide

“…De Kimpe and co-workers also reported the synthesis of N - tert -butanesulfinyl aziridines via the addition of allyl Grignard reagent to α-chloro N - tert -butanesulfinyl ketimines 1104a − c (eq ) . The aziridine products 1105a − c were obtained in good yields (65−95%) and with high diastereoselectivities (93:7 to >95:5).…”

“…A synthesis of cyclopropylamines via a proposed Favorskii-type rearrangement upon reaction of Grignard reagents with α-chloro N - tert -butanesulfinyl ketimines 329 was reported by De Kimpe and co-workers (Scheme ) . Optimization of the reaction conditions revealed that addition of 2.2 equiv of the Grignard reagent to the ketimine at −78 °C followed by subsequent warming to −40 °C provided the highest yields and diastereoselectivities of this interesting class of compounds.…”

“…In addition to the synthesis of aliphatic, α,β-unsaturated, aromatic, and heteroaromatic imine derivatives, the condensation of tert -butanesulfinamide with aldehydes and ketones bearing other functional groups has also been accomplished. For example, aliphatic imines bearing α-heteroatom functionality, including α-alkoxy aldimines 49 − and ketimines 50 , α-amino aldimines 51 , and ketimine 53 , and α-chloro aldimines and ketimines 54 (Figure ) have been reported. In cases where enantiomerically pure α-chiral aldehyde or ketone precursors were used, no epimerization at the α-stereocenter was detected.…”

Synthetic methods : Part (iii) Heteroatom chemistry

“…They utilised a chiral N-sulfinyl a-chloro ketimine 23 as the starting material. Reduction of 23 with borohydride reagents gave the corresponding aziridines, 51 and reaction of 23 with Grignard reagents gave either the corresponding aziridine or aminocyclopropane, 52 depending on the conditions (Scheme 20). Sulfinyl deprotection was achieved with dry hydrochloric acid in 1,4-dioxane, giving the corresponding hydrochloride salts with retention of configuration.…”

Allenylzinc reagents: new trends and synthetic applications

“…[114][115][116][117][118][119][120][121] So far, such imines have been intensively used in asymmetric synthesis. [122][123][124][125][126][127][128][129][130][131][132][133][134][135] The trans-acetylenic aziridines (AE)-33 are then formed as major isomers (trans : cis 4 91 : 9). Moreover, in all cases only one trans-aziridine (dr 4 98 : 2) was formed suggesting that the tBS-group has fully played its role of a chiral directing group.…”