The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3 + 2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e.Download high-res image (192KB)Download full-size image

The addition of phosphonate stabilized carbon nucleophiles to acyclic (pentadienyl)iron(1+) cations proceeds predominantly at an internal carbon to afford (pentenediyl)iron complexes. Those complexes bearing an electron withdrawing group at the σ-bound carbon (i.e., 13/14) are stable and isolable, while complexes which do not contain an electron withdrawing group at the σ-bound carbon undergo CO insertion, reductive elimination and conjugation of the double bond to afford cyclohexenone products (21/22). Deprotonation of the phosphonate 13/14 or 21 and reaction with paraformaldehyde affords the olefinated products. This methodology was utilized to prepare oxygenated carvone metabolites (±)-25 and (±)-26.

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.

A short, 4-step route to the scaffold of frondosin A and B is reported. The [1-methoxycarbonyl-5-(2′,5′-dimethoxyphenyl)pentadienyl]Fe(CO)3+ cation was prepared in two steps from (methyl 6-oxo-2,4-hexadienoate)Fe(CO)3. Reaction of this cation with isopropenyl Grignard or cyclohexenyllithium reagents affords (2-alkenyl-5-aryl-1-methoxycarbonyl-3-pentene-1,5-diyl)Fe(CO)3 along with other addition products. Oxidative decomplexation of these (pentenediyl)iron complexes, utilizing CuCl2, affords 6-aryl-3-methoxycarbonyl-1,4-cycloheptadienes via the presumed intermediacy of a cis-divinylcyclopropane.

The syntheses of 12 stereochemically diverse polyhydroxyl aminocyclohexane (“aminocyclitols”) derivatives are described. These short syntheses require 2–5 steps from N-(2,4-cyclohexadien-1-yl)phthalimide, which is prepared in two steps from tricarbonyl(cyclohexadienyl)iron(1+). The relative stereochemistries of the aminocyclitols were assigned by 1H NMR spectroscopy as well as X-ray diffraction analysis.

A route to the carbon skeleton of the proposed structure for heteroscyphic acid A was developed utilizing a Mn(III)/Cu(II) mediated oxidative free-radical cyclization and nucleophilic addition to (3-methylpentadienyl)iron(1+) cation.

A synthesis of the C9–C16 segment of ambruticin is described which relies on organoiron methodology to establish the 1,2,3-trisubstituted cyclopropane ring.

Tricarbonyl(1-methoxycarbonyl-5-phenylpentadienyl)iron(1+) hexafluorophosphate (7) was prepared in two steps from tricarbonyl(methyl 6-oxo-2,4-hexadienoate)iron. While addition of carbon and heteroatom nucleophiles to 7 generally occurs at the phenyl-substituted dienyl carbon to afford (2,4-dienoate)iron products, the addition of phthalimide proceeded at C2 to afford a (pentenediyl)iron product (18). Complex 18 was structurally characterized by X-ray diffraction analysis.The reaction of the title cation with carbon and heteroatom nucleophiles was examined. In general, the products arise from nucleophilic attack at C5 to give E,E- or E,Z-dienoate iron complexes. Addition of phthalimide anion proceeds at C2 of the cation to afford a (pentenediyl)iron complex, whose structure was confirmed by X-ray diffraction analysis.

A synthesis of (+)-decarestrictine L 1, a cholesterol biosynthesis inhibitory metabolite isolated from Penicilliumsimplicissimum, is described. Beginning from tri-O-acetyl-d-glucal, alkylation with trimethylaluminum introduced the axial methyl group at C-2 in a stereoselective fashion. Chain extension at the C-6 carbon was accomplished by generation of the primary tosylate, followed by displacement with cyanide anion. The synthesis of (+)-1 was completed in 13 steps and 6.3% overall yield.A total asymmetric synthesis of decarestrictine L, a cholesterol biosynthesis inhibitory metabolite isolated from Penicilliumsimplicissimum, from triacetyl-d-glucal is described. The synthesis is completed in 13 steps, with 6.3% overall yield.2,6-Anhydro-1,3,4-trideoxy-d-ribo-hept-3-enitol diacetateC11H16O5[α]D23=+109 (c 0.216, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2S,5S,6R2,6-Anhydro-1,3,4-trideoxy-d-arabino-hept-3-enitol diacetateC11H16O5[α]D23=+71.2 (c 0.332, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6R2,6-Anhydro-1,3,4-trideoxy-d-ribo-heptitol diacetateC11H18O5[α]D23=+50 (c 0.29, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2S,5S,6R2,6-Anhydro-1,3,4-trideoxy-d-arabino-heptitol diacetateC11H18O5[α]D23=+32 (c 0.26, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6R2,6-Anhydro-1,3,4-trideoxy-d-arabino-heptitolC7H14O3[α]D23=+43 (c 0.26, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6R2,6-Anhydro-1,3,4-trideoxy-4,6-O-(phenylmethylene)-d-arabino-heptitolC14H18O3[α]D23=+29 (c 0.20, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6R2,6-Anhydro-1,3,4-trideoxy-4-O-(phenylmethyl)-6-methylbenzenesulfonate-d-arabino-heptitolC21H26O5S[α]D23=+45 (c 0.28, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6R6-Methyl-3-(phenylmethoxy)-tetrahydro-2H-pyran-2-acetonitrileC15H19O2N[α]D23=+91 (c 0.32, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2R,5S,6Rcis-1-[(3′S,6′R)-Tetrahydro-6′-methyl-3′-(phenylmethoxy)-2′H-pyran-2′-yl]-2-propanoneC16H22O3[α]D23=+25.1 (c 0.432, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2′S,3′S,6′Rtrans-1-[(3′S,6′R)-Tetrahydro-6′-methyl-3′-(phenylmethoxy)-2′H-pyran-2′-yl]-2-propanoneC16H22O3[α]D23=+43.3 (c 0.448, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2′R,3′S,6′R1-[(2′R,3′S,6′R)-Tetrahydro-3-hydroxy-6′-methyl-2H-pyran-2-yl]-2-propanone (decarestrictine L)C9H16O3[α]D23=+21.1 (c 0.452, CHCl3)Source of chirality: chiral pool (triacetyl-d-glucal)Absolute configuration: 2′R,3′S,6′R

Addition of allyldiisopinocampheylborane to racemic (dienal)iron complexes, followed by oxidation, affords diastereomeric (1,4,6-trien-3-ol)iron complexes with moderate to low enantioselectivity. The high enantioselectivity typically observed for this allylborane reagent is attenuated by steric interaction between the Fe(CO)3 group and the chiral isopinocampheyl groups. Further diminution of the enantioselectivity is observed for dienal complexes in which one rotomer predominates.

The syntheses of 12 stereochemically diverse polyhydroxyl aminocyclohexane (“aminocyclitols”) derivatives are described. These short syntheses require 2–5 steps from N-(2,4-cyclohexadien-1-yl)phthalimide, which is prepared in two steps from tricarbonyl(cyclohexadienyl)iron(1+). The relative stereochemistries of the aminocyclitols were assigned by 1H NMR spectroscopy as well as X-ray diffraction analysis.

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.

A short, 4-step route to the scaffold of frondosin A and B is reported. The [1-methoxycarbonyl-5-(2′,5′-dimethoxyphenyl)pentadienyl]Fe(CO)3+ cation was prepared in two steps from (methyl 6-oxo-2,4-hexadienoate)Fe(CO)3. Reaction of this cation with isopropenyl Grignard or cyclohexenyllithium reagents affords (2-alkenyl-5-aryl-1-methoxycarbonyl-3-pentene-1,5-diyl)Fe(CO)3 along with other addition products. Oxidative decomplexation of these (pentenediyl)iron complexes, utilizing CuCl2, affords 6-aryl-3-methoxycarbonyl-1,4-cycloheptadienes via the presumed intermediacy of a cis-divinylcyclopropane.