Iron-Mediated Preparation of Vinylcyclopropanecarboxylates:  Scope, Mechanism, and Applications

Abstract

The addition of stabilized carbon nucleophiles to tricarbonyl(1-methoxycarbonylpentadienyl)iron(1+) cation (1a) proceeds via attack at C2 on the face of the ligand opposite the Fe(CO)(3) group to generate tricarbonyl(pentenediyl)iron complexes 2. Oxidation of complexes 2 affords vinylcyclopropanecarboxylates in good yield. In general, the relative stereochemistry about the cyclopropane ring reflects reductive elimination with retention of configuration. In cases where the C2 substituent is bulky (i.e., 2b) the major cyclopropane product 9b represents ring closure with inversion at C3. A mechanism involving pi-sigma-pi rearrangement of the initially oxidized (pentenediyl)iron species is proposed to account for these results. Experiments which probe the stereochemistry of deuterium labeling in the vinyl group of the vinylcyclopropanecarboxylate products were carried out, and these results are consistent with the proposed mechanism. This methodology for the preparation of vinylcyclopropanecarboxylates was applied to the synthesis of 2-(2'-carboxycyclopropyl)glycines (+)-22 and (-)-23 and the cyclopropane triester (-)-26.

Recent Applications of Acyclic (Diene)iron Complexes and (Dienyl)iron Cations in Organic Synthesis

“…[36] Alternatively, the thermal reaction of (vinylketene)iron complex 72 with dimethylfumarate generated the (pentenediyl)iron complex 71b . [37] Oxidation of either 71a or 71b with ceric ammonium nitrate gave the vinylcyclopropanecarboxylates 73a or b .…”

“…[37] Oxidation of either 71a or 71b with ceric ammonium nitrate gave the vinylcyclopropanecarboxylates 73a or b . [36a, 37] Since this is formally an oxidatively induced-reductive elimination, the reaction generally proceeds with retention of configuration at the two centers undergoing C–C bond formation.…”

“…[36a] Decomplexation of the mixture of diastereomers afforded vinylcyclopropanecarboxylate (2′ S )- 78 as an inseparable mixture of diastereomers at the nitroacetate carbon. Transformation of the diastereomeric mixture (2′ S )- 78 into the individual 3-ethyl CCGs (−)- 79 and (+)- 80 required reduction of the vinyl and nitro groups, conversion of the amines into a separable mixture of diphenylmethylene imines,[40] hydrolysis of the separate diphenylmethylene imines and the methyl esters and finally generation of the free bases.…”

Benzophenone Schiff bases of glycine derivatives: Versatile starting materials for the synthesis of amino acids and their derivatives

“…An interesting use of benzophenone Schiff base derivatives was reported by Donaldson (Scheme 26). 69 The amino ester diasts-55, a mixture of diastereomers, was an intermediate in the synthesis of conformationally restricted analogs of glutamate. When it was not possible to separate the mixture of diastereomers into its individual diastereomers, diasts-55 was converted into its benzophenone imine, which was readily separable by column chromatography to give the individual diastereomers (-)-55a and (+)-55b.…”

Recent advances in the total synthesis of cyclopropane-containing natural products

“…13 This methodology, first reported by the Donaldson group in 2003, rests its foundation on the addition of a carbon nucleophile to the cationic iron complex 8 to produce a neutral organo-iron species 10. 14 Mechanistically, an initial single electron transfer from the organometallic reagent (e.g. MeLi) to the cationic iron-complex 8, followed by a homolytic carbon-carbon bond formation at the C-2 position, was proposed for this transformation.…”