De Novo Synthesis of Racemic Spirocyclopropane‐Annelated 2‐Deoxyhexose Derivatives

Abstract

High‐pressure‐induced inverse‐electron‐demand hetero‐Diels−Alder reactions of ethyl trans‐4‐ethoxy‐2‐oxo‐3‐butenoate (2a) and methyl trans‐4‐benzyloxy‐2‐oxo‐3‐butenoate (2b) with benzyl (cyclopropylidenemethyl) ether (1) each yielded mixtures of two separable diastereomeric esters 7a (64%) and 7b (80%) which, in three subsequent steps, led to the 3‐ethylated and 3‐benzylated α‐ and β‐anomeric benzyl spiro[2‐deoxy‐(D,L)‐arabino‐hexopyranoside‐2,1′‐cyclopropanes] α‐10a,b and β‐10a,b, respectively. The relative configuration of β‐10a was proved by an X‐ray crystal structure analysis. Deprotection of β‐10b was achieved by Pd‐catalyzed hydrogenation in dimethylacetamide leading to spiro[2‐deoxy‐α/β‐2‐(D,L)‐arabino‐hexopyranoside‐2,1′‐cyclopropane] (4). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Thermally Induced [2+2] Cycloadditions of (Benzyloxymethylene)cyclopropane with Alkylidenemalononitriles

“…Recently, we found that [2+2] cycloadditions of (alkoxymethylene)cyclopropanes 1, which are easily accessible and storable at room temperature, [8] with imines proceeded at ambient pressure [Equation (1)]. [9] We envisioned that the formation of the zwitterionic intermediate A, in which the cation center is doubly stabilized by the cyclopropyl and the alkoxy groups, facilitated the cycloaddition.…”

Synthesis of Methylene‐ and Alkylidenecyclopropane Derivatives

“…For example, the use of t-BuOK or TEA as a base in this methodology has allowed products 58a-c to be obtained in good yields, as depicted in Scheme 24. [42] In particular, the highly strained and unusually tetrasubstituted alkene bicyclopropylidene 59 [8f,43] could be prepared by de Meijere et al in up to 82% yield starting from the corresponding 1-bromo-1-cyclopropylcyclopropane (Scheme 24). [44] In the last decade, a large number of nucleoside analogues based on a methylenecyclopropane structure have been synthesized by the group of Zemlicka with the aim of evaluating their broad-spectrum antiviral activities.…”

Cyclopropyl Building Blocks for Organic Synthesis, 139. Ethyl Cyclopropylidenepyruvate as a Novel Multifunctional Cyclopropyl Building Block: Facile Preparation and Basic Reaction Patterns

“…After stirring at ambient temperature for 2 h, the reaction was quenched by addition of 5 % aqueous H 2 SO 4 (2 mL), the organic layer was separated, and the aqueous phase was re-extracted with diethyl ether (3 2 mL). The combined organic phases were washed with brine (2 5 mL) and dried with MgSO 4 . Solvent removal left a crude product, which was purified by chromatography on silica gel.…”

“…A series of 1'-substituted methylenecyclopropane derivatives 1 (Scheme 1) has demonstrated a range of reactivity patterns potentially useful for the synthesis of certain natural products and spirocyclopropanated analogues of biologically active compounds. [2,3] For example, bicyclopropylidene (1a) has been employed in various palladium-catalyzed cascade reactions, [2] and (benzyloxymethylene)-cyclopropane (1b) was used in the synthesis of a spirocyclopropane-annelated sugar [4] as well as interesting azetidine derivatives. [5] Several previously prepared acceptor-substituted methylenecyclopropanes 1c-h come along with a particularly broad spectrum of applications.…”