Synthesis of cyclopropanes via organoiron methodology: stereoselective preparation of cis-2-(2’-carboxycyclopropyl)glycine

A stereoselective route to cis-2-(2′-carboxycyclopropyl)glycine has been developed. exo-Nucleophilic addition to the (bicyclo[5.1.0]octadienyl)iron(1+) cation establishes the relative stereochemistry at the cyclopropane ring and the α-stereocenter. Subsequent removal of the metal and cleavage of the cyclic diene gave the protected target 10, which upon hydrolysis gave 1. A stereoselective route to cis-2-(2′-carboxycyclopropyl)glycine has been developed. exo-Nucleophilic addition to the (bicyclo[5.1.0]octadienyl)iron(1+) cation establishes the relative stereochemistry at the cyclopropane ring and the α-stereocenter

Reactivity of (Bicyclo[5.1.0]octadienyl)iron(1+) Cations: Application to the Synthesis of cis-2-(2’-carboxycyclopropyl)glycines

The addition of carbon and heteroatom nucleophiles to (bicyclo[5.1.0]octadienyl)Fe(CO)2L+ cations 5 or 8 (L = CO, PPh3) generally proceeds via attack at the dienyl terminus on the face of the ligand opposite to iron to generate 6-substituted (bicyclo[5.1.0]octa-2,4-diene)iron complexes (11 or 13). In certain cases, these products are unstable with respect to elimination of a proton and the nucleophilic substituent to afford (cyclooctatetraene)Fe(CO)2L (4 or 7). Decomplexation of 13f, arising from addition of phthalimide to 8, gave N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (19). Oxidative cleavage of 19 (RuCl3/NaIO4) followed by esterification gave the cyclopropane diester 22, which upon hydrolysis gave cis-2-(2‘-carboxycyclopropyl)glycine (CCG-III, 18) (eight steps from 4, 43% overall yield). This methodology was also utilized for preparation of stereospecifically deuterated CCG-III (d-18) and optically enriched (−)-18. Deprotonation of 22 resulted in cyclopropane ring opening to afford the benzoindolizidine (23)

Crystal structure of \u3cem\u3ecis\u3c/em\u3e-2-(2-carboxycyclopropyl)-glycine (CCG-III) monohydrate

The title compound, C6H9NO4·H2O [systematic name: (αR,1R,2S)-rel-α-amino-2-carb­oxy­cyclo­propane­acetic acid monohydrate], crystallizes with two organic mol­ecules and two water mol­ecules in the asymmetric unit. The space group is P21 and the organic mol­ecules are enanti­omers, thus this is an example of a `false conglomerate\u27 with two mol­ecules of opposite handedness in the asymmetric unit (r.m.s. overlay fit = 0.056 Å for one mol­ecule and its inverted partner). Each mol­ecule exists as a zwitterion, with proton transfer from the amino acid carb­oxy­lic acid group to the amine group. In the crystal, the components are linked by N-H···O and O-H···O hydrogen bonds, generating (100) sheets. Conformationally restricted glutamate analogs are of inter­est due to their selective activation of different glutamate receptors, and the naturally occurring (+)-CCG-III is an inhibitor of glutamate uptake and the key geometrical parameters are discussed

Synthesis of Cyclopropanes via Organoiron Methodology: Preparation and Rearrangement of Divinylcyclopropanes

Addition of alkenyl Grignard reagents to (1-methoxycarbonylpentadienyl)iron(1+) cation generates the corresponding (2-alkenylpent-3-en-1,5-diyl)iron complexes. Oxidatively induced-reductive elimination of these complexes gives divinylcyclopropanes which can undergo subsequent Cope rearrangement to give 1,4-cycloheptadienes

Sprectral data for Generation of Molecular Complexity from Cyclooctatetraene Using Dienyliron and Olefin Metathesis

Spectral data used in the course of researching Generation of molecular complexity from cyclooctatetraene using dienyliron and olefin metathesis methodology . Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis

Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system

A diastereoselective route to the 5,7,5-tricyclic core of the guianolides is presented. This route relies on Cope rearrangement of a divinylcyclopropane prepared by alkenyl Grignard addition to a (pentadienyl)iron(+1) cation, followed by oxidative decomplexation. An additional key reaction involves oxidative rearrangement of a 3,4-epoxy-1,7-diol to generate a γ-lactone. The relative stereochemistry of this product was established by X-ray crystallography

Reactivity of (2-alkenyl-3-pentene-1,5-diyl)iron complexes: preparation of functionalized vinylcyclopropanes and cycloheptadienes

The reactivity of (2-alkenyl-3-pentene-1,5-diyl)iron complexes toward olefin metathesis, cycloaddition, and mild oxidations (MnO2 or mCPBA) was examined. Cycloaddition reactions were observed to occur with modest diastereoselectivity (33−63% de). Decomplexation of the (3-pentenediyl) ligand may be accomplished by oxidation with either CAN or alkaline hydrogen peroxide to afford vinylcyclopropanecarboxylates or divinylcyclopropanecarboxylates. Reduction of the latter, followed by Cope rearrangement generates cycloheptadienylmethanols. These studies demonstrate that (2-alkenyl-3-pentene-1,5-diyl)iron complexes can serve as organometallic scaffolds for the preparation of a wide variety of structural motifs containing up to 5 contiguous stereocenters

Generation of Molecular Complexity from Cyclooctatetraene Using Dienyliron and Olefin Metathesis Methodology

Transformation of the simple hydrocarbon cyclooctatetraene into a variety of polycyclic skeletons was achieved by sequential coordination to iron, reaction with electrophiles followed by allylated nucleophiles, decomplexation and olefin metathesis

Preparation of Cyclopropanes via Organoiron Methodology

The cyclopropane moiety is found in a wide variety of the natural products, from small amino acid molecules to the structurally intriguing (and synthetically challenging) polycyclopropanes. This is perhaps somewhat surprising, due to the inherent instability associated with simplest of carbocyclic rings. Cyclopropanes are unique in both their bonding and reactivity. In fact it is the sp2-like character of the cyclopropane carbons that ultimately determines their reactivity. Indeed, most reactions associated with alkenes have similar counterparts in cyclopropane chemistry. At the same time, organoiron chemistry is dominated by n-olefin complexes, and it somehow seems intuitive that cyclopropanes might be prepared ( or undesirably destroyed) via stoichiometric transition metal chemistry. Because nucleophilic addition to cationic organoiron complexes is often highly stereoselective, in principle\u27it also ought to be possible to prepare functionalized 3-membered rings in a stereocontrolled fashion. This work details an organoiron approach to the synthesis of cyclopropanes. Chapter 1 deals primarily with the synthesis and reactivity of (bicyclo[5.l.O]octadienyl)iron( l +) cations. The knowledge gained was.used to synthesize CCG-III, a small molecule neurotransmitter. Chapter 2 has a more general methodological focus; the synthesis of functionalized divinylcyclopropanes. These molecules serve as precursors to cycloheptadienes (via a Cope rearrangement)

Preparation of cyclopropanes via organoiron methodology

The cyclopropane moiety is found in a wide variety of the natural products, from small amino acid molecules to the structurally intriguing (and synthetically challenging) polycyclopropanes. This is perhaps somewhat surprising, due to the inherent instability associated with simplest of carbocyclic rings. Cyclopropanes are unique in both their bonding and reactivity. In fact it is the sp2 -like character of the cyclopropane carbons that ultimately determines their reactivity. Indeed, most reactions associated with alkenes have similar counterparts in cyclopropane chemistry. At the same time, organoiron chemistry is dominated by π-olefin complexes, and it somehow seems intuitive that cyclopropanes might be prepared (or undesirably destroyed) via stoichiometric transition metal chemistry. Because nucleophilic addition to cationic organoiron complexes is often highly stereoselective, in principle it also ought to be possible to prepare functionalized 3-membered rings in a stereocontrolled fashion. This work details an organoiron approach to the synthesis of cyclopropanes. Chapter 1 deals primarily with the synthesis and reactivity of (bicyclo[5.1.0]octadienyl)-iron(1+) cations. The knowledge gained was used to synthesize CCG-III, a small molecule neurotransmitter. Chapter 2 has a more general methodological focus; the synthesis of functionalized divinylcyclopropanes. These molecules serve as precursors to cycloheptadienes (via a Cope rearrangement)