Jonathan C. Walker

The asymmetric synthesis of β-lactams : Stereocontrolled Asymmetric Tandem Michael Additions and Subsequent Alkylations of E-[(η5-C5H5)Fe(CO)(PPH3)COCH = CHME]. X-ray Crystal Structure of (RS)-E-[(η5-C5H5) Fe (CO) (PPH3) COCH = CHME]

Abstract Michael addition of methyllithium to the E-crotonyl complex (RS)-[η5-C5H5)Fe(CO)-(PPh3)COCHCHMe] followed by trapping of the resultant enolate with methyl iodide gives (RS)-[(η5-C5H5)Fe(CO)(PPh3)COCH(Me)CHMe2] (d.e. > 100:1), also generated by treatment of (RS)-[(η5-C5H5)Fe(CO)(PPh3)COCH2CH(OMe)2] with three equivalents of methyllithium and methyl iodide. Addition of n -butyllithium to the (RS)-E-crotonyl complex followed by protonation with methanol occurs with high diastereoselectivity. Quenching with methyl iodide gives (RS)-[(η5-C5H5)Fe(CO)(PPh3)COCH(Me)CH(Me) n -Bu], also generated by treating either diastereoisomer of [(η5C5H5)Fe(CO)(PPh3)COCH2CH(Me)OMe] with two equivalents of n -butyllithium and methyl iodide. Decomplexatlon gives the known erythro -2,3-dimethyl-heptanoic acid. Similarly, Michael addition of lithium benzylamide and electrophilic quenching with methanol or methyl iodide occurs with high diastereoselectivity and gives upon decomplexation, 4-methyl- and cis -3,4-dimethyl-N-benzyl-β-lactams respectively. The stereochemical results are rationalised by addition occurring to the E-crotonyl complex in the anti (CO to CO) and cisoid conformation and subsequent alkylation of the unhindered face of the E-enolate generated. Confirmation is provided by an X-ray crystal structure analysis of (RS)-E-[(η5-C5H5)Fe(CO)(PPh3)COCHCHMe]. When repeated with the optically pure (S)-E-crotonyl complex, decomplexation gives essentially optically pure (2R) ,(3R)-(-)-N-benzyl-2,3-dimethylheptanamide, (4S)-(-)-4-methyl- and (3R),(4S)-(-)- cis -3,4-dimethyl-N-benzyl-β-lactams.

The asymmetric synthesis of β-lactams. Stereocontrolled asymmetric tandem Michael additions and alkylations of α,β-unsaturated acyl ligands bound to the chiral auxiliary [(η5-C5H5)Fe(CO)(PPh3)]

Michael addition of lithium benzylamide to the enantiomerically pure (S)-E-crotonyl complex of [(η5-C5H5)Fe(CO)(PPh3)] followed by trapping of the resultant enolate with methyl iodide or methanol occurs with high diastereoselectivity and gives after decomplexation the essentially optically pure (3R), (4S)-(−)-3,4-dimethyl- and (4S)-(−)-4-methyl-N-benzyl-β-lactams respectively. Similarly, tandem addition of lithium benzylamide and methylation of the corresponding enantiomerically pure R-(−)-acryloyl complex gave after decomplexation the essentially optically pure (3S)-(−)-3-methyl-N-benzyl-β-lactam.

Stereoselective synthesis of erythro-β-hydroxy carboxylic acids via iron acyl complexes

Abstract β-Hydroxy acyl ligands bound to (η 5 -C 5 H 5 )Fe(CO)(PPh 3 ) are stereoselectively alkylated on the α-carbon to give after decomplexation erythro -β-hydroxy carboxylic acids.

Stereocontrolled tandem alkylations: Michael additions and subsequent alkylations of α,β-unsaturated acyl ligands bound to [(η5-C5H5)Fe(CO)(PPh3)]

α,β-Unsaturated acyl complexes of [(η5-C5H5)Fe(CO)(PPh3)] can be prepared by the Peterson olefination reaction and are found to undergo tandem stereoselective Michael additions and subsequent methylations which result in the stereocontrolled synthesis of α- and β-substituted iron acyl complexes.

Synthesis and Characterisation of E and Z α,β-Unsaturated Acyl Complexes [(η5-C5H5)Fe(CO)(PPh3)(COCH=CHR)] (R=H, Me, Et, n-Bu, t-Bu, Ph, vinyl,2-furyl)

Abstract α,β-Unsaturated acyl complexes of the chiral auxiliary [(η5-C 5 H 5 )Fe(CO)(PPh 3 )] can be generated in high yield as readily separable mixtures of E and Z isomers by the Peterson olefination reaction between [(η 5 -C 5 H 5 )Fe(CO)(PPh 3 )COCH 2 SiMe 3 ] and aldehydes RCHO (R=H, Me, Et, n -Bu, t -Bu, Ph, vinyl, 2-furyl). The Wittig reaction between [(η 5 -C 5 H 5 )Fe(CO)(PPh 3 )COCH=PMe 3 ] and benzaldehyde stereoselectively generates E-[(η5-C 5 H 5 )Fe(CO)(PPh 3 )COCH=CHPh]. α-Trimethyl-silylation of both diastereoisomers of the β-hydroxy complexes [(η 5 -C 5 H 5 )Fe(CO)(PPh 3 )COCH 2 CH(OH)R] gives completely stereoselectively the corresponding E α,β-unsaturated acyl complexes [(η 5 -C 5 H 5 )Fe-(CO) (PPh 3 )COCH=CHR], These E α,β-unsaturated acyl complexes are also formed stereoselectively, in high yield via sodium hydride induced elimination of methanol from the β-methoxy complexes [(η 5 -C 5 H 5 )Fe(CO)(PPh 3 )COCH 2 CH(OMe)R] (R=H, Me, Et, n -Bu, Ph, vinyl, 2-furyl).

Base promoted rearrangements of cyclopentadienylacyl- and -carboxyalkyl-metal complexes

Treatment of the complexes [(η5-C5H5)Fe(CO)(PPh3)COCH2R] and [(η5-C5H5)Fe(CO)(PPh3)CO2R] with n-butyllithium followed by methyl iodide gives the rearranged products [(η5-C5H4COCH2R)Fe(CO)(PPh3)Me] and [(η5-C5H4CO2R)Fe(CO)(PPh3)Me] respectively; the former reactions are stereospecific.

Asymmetric Diels–Alder reactions: (S)-(+)-[(η5-C5H5)Fe(CO)(PPh3)COCHCH2] as a chiral acrylate dienophile equivalent

The zinc chloride-mediated Diels–Alder reaction between (S)-(+)-[(η5-C5H5)Fe(CO)(PPh3)COCHCH2] and cyclopentadiene yielded (2S)-(–)-bicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid which was converted into the corresponding optically pure iodolactone.

Chiral dienolates : Stereoselective formation and α-alkylation of the lithium dienolates derived from (RS)-Z-[(n5-C5H5)Fe(CO)(PPh3)COCHCHCH2R] (RMe,Et,n-pr) and (RS)-[(n5-C5H5)Fe(CO)(PPh3)(COCHCMme2)]

Abstract The acyl ligands Z-(COCHCHCH2-R)(RMe,Et, n -Pr) and (COCH-CMe2) bound to the chiral auxiliary [(n5 -C5H5)Fe(CO)(PPh3)] undergo exclusive γ-deprotonation to form the corresponding dienolates which react with electrophiles regio- and stereoselectively at the α-position to give in most cases single diastereoisomers of the corresponding α-substituted-βγ-unsaturated acyl complexes, together with in the former cases complete control over the β,γ-double bond geometry (E).

Chiral dienolates: formation and stereoselective α-alkylation of the lithium dienolate derived from (Z)-[(η5-C5H5)Fe(CO)(PPh3)COCHCHMe]. X-Ray crystal structure of (RS)-(Z)-[(η5-C5H5)Fe(CO)(PPh3)COCHCHMe]

An X-ray crystal structure analysis of (RS)-(Z)-[(η5-C5H5)Fe(CO)(PPh3)COCHCHMe](2) shows that the crotonoyl group adopts a cisoid conformation in the solid state. In solution it is the cisoid conformation that is deprotonated by butyl-lithium to give the corresponding dienolate (3). Alkylation (Mel, Etl, or PhCH2Br) of the lithium dienolate (3) occurs regiospecifically in the α-position to give stereoselectively the single diastereoisomers (RS,SR)-[(η5-C5H5)Fe(CO)(PPh3)COCHRCHCH2](R = Me, Et, or PhCH2). Protonation of the dienolate (3) gives the β,γ-unsaturated acyl complex [(η5-C5H5)Fe(CO)(PPh3)COCH2CHCH2] exclusively.

Determination of the absolute configuration and optical purity of [(η5-C5H5)Fe(CO)(PPh3)COMe]; X-ray crystal structure of (R)-{(η5-C5H5)Fe(CO)(PPh3)COCH2CH2O[(R)-menthyl]}

The enantiomeric purities of (R)-(–)-[(η5-C5H5)Fe(CO)(PPh3)COMe](1)[α]54622–288°(c 0.04, C6H6) and S-(+)-(1)[α]54622+288°(c 0.04, C6H6) are established by two independent methods and the absolute configurations assigned by an X-ray structure analysis of (R)-{(η5-C5H5)Fe(CO)(PPh3)COCH2CH2O [(R)-menthyl]}.