Ti‐Mediated Synthesis of Aminocyclopropyl‐Substituted Carbohydrates

Abstract

Carbohydrates bearing aminocyclopropyl moieties were conveniently prepared from the corresponding nitriles by titanium-mediated addition of Grignard reagents. A wide range of protective groups are tolerated.

Transition metals in organic synthesis: Highlights for the year 2005

“…Titanium mediated intramolecular cyclopropanations of alkene tethered amides [762]. A titaniummediated cyclopropanation of nitriles with Grignard reagents to give amino-substituted cyclopropanes was described [763]. Cyclopropanation of alkenes was reported using 2-(1-alkyne-1-yl)-2-(trialkylsilyl)-1,3-dithianes and a titanium catalyst (Eq.…”

Synthesis of a 5-Spirocyclopropyl Deoxyrhamnojirimycin as a Constrained Naringinase Inhibitor

“…14 The addition of ethylmagnesium bromide at low temperature (-78°C), followed by warming to room temperature gave 9 in increased yield ( Table 1, entries 3 and 4), as previously noted for other nitriles, 15 including those derived from carbohydrates. 16 Here, again, the addition of a Lewis acid had a beneficial effect on the ring-contraction step (Table 1, entry 4).…”

Synthetic Access to the First Spirocyclopropyl Iminosugar

“…Recently, we described an application of this method to polyfunctionalized substrates such as sugar-derived nitriles. 8 A range of protecting groups like acetals, esters or ethers were shown to be well tolerated under the reaction conditions. Particularly, 2,3,5-tri-O-benzyl-4-O-pivaloyl-D-arabinononitrile (7), prepared in two steps from commercially available 2,3,5-tri-O-benzyl-D-arabinose ( 5), was smoothly transformed into the corresponding cyclopropylamine 9 by reaction with EtMgBr and Ti(Oi-Pr) 4 (Scheme 1).…”

“…Scheme 1 Synthesis of sugar-derived cyclopropylamine 9. 8 In an initial approach we envisioned the synthesis of 4 by simple functional group transformations starting from the cyclopropylamine 9 (Scheme 2). To this purpose, the deprotection of the pivaloyl protecting group (MeONa/ MeOH) was followed by mesylation of the free hydroxyl group (MsCl, pyridine).…”