William A. Donaldson

Model studies toward the synthesis of macrolactin A: Organoiron methodology for introduction of the C1–C11 and C16–C24 segments

Abstract Preparation of the Fe(CO)3 complexed C1–C11 and the C16–C24 segments of macrolactin A has been accomplished from (sorbaldehyde)Fe(CO)3 in 4 steps and 5 steps respectively.

Synthetic studies directed toward the phorboxazoles: preparation of the C3–C15 bisoxane segment and two stereoisomers

Abstract A synthetic approach to the C3–C15 segment of the cytotoxic marine metabolite phorboxazoles is described. This segment consists of a methylene linked bisoxane structure. The first pyran ring was constructed by a Lewis acid catalyzed diene–aldehyde cyclocondensation. The β-C-glucoside substitution pattern of this ring was established by a stereoselective allylation. Ozonolysis of vinyl group and enantioselective allylation of the racemic aldehyde generated two separable homoallylic alcohols (−)-22 and (+)-23 . The Moshers esters of each alcohol were determined to be >90% de. Reaction of (−)-22 with acryloyl chloride, followed by ring closing metathesis gave the dihydro-2-pyrone target (−)-5 . Mitsunobu inversion of (+)-23 with p-nitrobenzoic acid, hydrolysis, and esterification with acryloyl chloride and ring closing metathesis gave pseudoenantiomeric segment (+)-6 .

Stoichiometric Applications of Acyclic π-Organoiron Complexes to Organic Synthesis

The application of acyclic (diene)iron complexes and (pentadienyl)iron cations in organic synthesis has steadily increased over the past 20 years. This is due to their ease of preparation, their stability toward a wide variety of reaction conditions, the manifold method for removal of the Fe(CO)3 group, and the low cost of iron carbonyls. The (tricarbonyl)iron adjunct may serve in three capacities: i) as a protecting group for conjugated dienes, ii) to direct the formation of chiral centers adjacent to the complexed dient, and iii) to stabilize the formation of positive charge adjacent ot the complexed diene (i.e. pentadienyl cations). Specific examples of these attributes will be presented in this review. One of the advantages of stoichiometri c organometallic reagents is the ability to repeatedly utilize the same metal center to control a number of different bond forming reactions. Six examples will be presented which demonstrate this potential for acyclic (diene)iron complexes and (pentadienyl) iron cations.

Enantioselective synthesis of the C11-C24 segment of macrolactin a via organoiron methodology

Abstract The enantioselective synthesis of the Fe(CO) 3 completed C11-C24 segment of macrolactin A has been accomplished from rac -(methyl 6-oxo-2,4-hexadienoate)Fe(CO) 3 in 11 steps (>50% ee).

Phorboxazole synthetic studies: the C3–C15 bis-oxane segment

Abstract The enantioselective synthesis of the C3–C15 bis-oxane segment of the phorboxazoles has been accomplished from 3- t -butyldiphenylsilyloxypropanal in 9 steps (>90% ee).

Development of Organoiron Methodology for Preparation of the Polyene Natural Product Macrolactin A

Abstract Methodology for the synthesis of the C7–C13 segment ( 19 ) and C14–C24 segment ( 41 ) of macrolactin A have been developed. Dicarbonyl(methyl 7-nitro-2 E ,4 Z -heptadienoate)triphenylphosphineiron ( 19 ) is prepared by nucleophilic addition to a (1-methoxycarbonylpentadienyl)iron cation. The C23 stereocenter of 41 is established by introduction of a C20 stereocenter, chirality transfer from C20 to C23 followed by (diene)iron mediated selective ionic reduction of the C20 hydroxyl. The C15 stereocenter may be established by nitrile oxide–olefin cyclocondensation.

(η5-1-substituted-pentadienyl) (tricarbonyl)iron(+1) cations:Reactivity with malonate nucleophiles

Abstract The title compounds react with alkynyl cuprates via attack at the unsubstituted terminus to afford (η4-trans, cis-1,3,6-dienyne)Fe(CO)3 complexes. The regioselectivity of this attack appears to be sterically controlled.

Reactivity of carbon nucleophiles with disubstituted tricarbonyl(pentadienyl)iron(1+) cations: Application to the synthesis of lasiol and epi-lasiol

Abstract The reactions of 1,2-dimethyl-, 1-phenyl-2-methyl-, 1,4-dimethyl-, and 1-phenyl-4-methyl- substituted tricarbonyl(pentadienyl)iron(1+) cations ( 3a, 3b, 4a, 4b respectively) with lithium dimethylcuprate and with sodium dimethylmalonate were examined. Regiospecific nucleophilic attack was observed in cases where the directing effects of the two substituents were matched. The reaction of 4a with sodium dimethyl methylmalonate was examined, and the product was subsequently transformed into a mixture of epi-lasiol and lasiol, a terpene with a novel rearranged skeleton.

Synthesis and reactivity of (tricarbonyl)-(η5-2-methylpentadienyl)iron( + 1) cation

Abstract The (tricarbonyl)(η 5 -2-methylpentadienyl)iron(+1) cation was prepared by the protonation of (tricarbonyl)(4-methyl-2,4-pentadienol)iron. Reaction of the cation with H 2 O, allyl-TMS, NaBH 3 CN, PPh 3 , malonate and 3-furyl cuprate gave (η 4 -1,3-diene)Fe(CO) 3 complexes. The regioselectivity for the nucleophilic attack appears to be sterically controlled.

Reactivity of 1-substituted (pentadienyl)iron(1+) cations: Regioselectivity for addition of malonate nucleophiles; formation of (pentenediyl)- and (diene) iron complexes

Abstract The reaction of six 1-substituted (pentadienyl)iron cations ( 1–6 ) with malonate anions was examined. The electronic nature of substituents present on the pentadienyl ligand, the steric bulk of the malonate anion, and the peripheral ligands about the iron metal were varied. (Pentenediyl)- and/or (diene)iron complexes, resulting from attack at either an internal (C2/C4) or terminal (C1/C5) pentadienyl carbon, were isolated as products. These results indicate that strongly electron withdrawing substituents direct malonate attack at the internal pentadienyl site, while strongly electron donating substituents direct malonate attack at the terminal pentadienyl site. The single crystal X-ray diffraction analysis of two (pentenediyl)iron complexes ( 7a and 7b ) are reported.