Efficient synthesis of protected cyclopropyl β-aspartylphosphates

Abstract

The in situ reaction of protected dehydroamino acids with derivatives of vinyldiazomethane leads to good to excellent yields of vinyl cyclopropanes via 3 + 2 dipolar cycloaddition followed by N(2) extrusion. Chromatographic separation of the cyclopropane diastereomeric products, followed by characterisation by (1)H NMR and X-ray crystallography allowed the cis and trans diastereomers to be easily identified. Oxidative cleavage of the vinyl moiety then led directly to protected cyclopropane aspartic acid derivatives in three steps from commercially available materials. These compounds were converted to protected methylenephosphonate, difluoromethylenephosphonate and phosphoramidate analogues of [small beta]-aspartyl phosphate.

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

“…Direct methods to effectively synthesize functionalized enantio- and diastereoenriched cyclopropyl amines remain challenging, however. Existing routes to prepare amino cyclopropyl carbinols suffer from either low yields94 (Scheme 5, A), low diastereoselectivities95, 96 (Scheme 5, B) or are not enantioselective 97–99…”

Helical screw‐sense preferences of peptides based on chiral, Cα‐tetrasubstituted α‐amino acids

“…Overall, two pairs of enantiomers give rise to two possible dispositions ( cis or trans ) of the β‐substituent relative to the α‐amino group. Although this class of compounds has attracted considerable interest, the available structural information is mostly limited to N‐ and C‐protected / blocked amino acid derivatives . In this set of structures, heterogeneous in terms of terminal groups and nature of the β‐substituent, apart from a few examples of the semi ‐extended conformation, β‐substituted Ac 3 c overwhelmingly adopt a distorted helical conformation.…”

Functionalized fluoroalkyl and alkenyl silanes: Preparations, reactions, and synthetic applications

“…Later on deprotonation and silylation of difluoromethylphosphonate 86 [26], bromine-lithium [27] and bromine-magnesium [28] exchange reactions of bromodifluoromethylphosphonate 85 followed by silylation with TMSCl, and sulfur-lithium [29] exchange and silylation of difluoro(methylthio)methylphosphonate 87 were employed for the purpose (Scheme 20). Most favorably in laboratory scale preparation, the reaction of easily available bromide 85 with either butyl lithium or Grignard reagent followed by silylation with TMSCl provides 84a in over 90% yield.…”

“…The reaction of 84a with naphthyl aryl sulfoxide 74 provided difluoroethylphosphate 89 in high diastereoselectivity (de > 96%) via rearrangement of the phosphonate group from carbon to oxygen in which intramolecular nucleophilic attack of alkoxide anion of the intermediate to the phosphorus atom of the difluorophosphonate moiety may take place (Scheme 22) [22]. The reaction of 84a with cyclopropyl aldehyde 90 (trans-cis = 90:10) followed by DessMartin oxidation provided trans-91 as a sole product [29]. Optically active glyceraldehyde derivative 92 was transformed to 93 [27].…”