Isabelle M. Dordor-Hedgecock

Chiral propionate enolate equivalents for the stereoselective synthesis of threo- or erytho-α,-methyl-β-hydroxy acids

Abstract The aluminium and copper enolates derived from (η5-C5H5)Fe(CO)(PPh3)COCH2CH3 are chiral propionate enolate equivalents which on reaction with aldehydes (RCHO, RMe.Et,iPr,tBu) provide stereoselective syntheses of threo- and erytho-α-methyl-β-hydroxy acids respectively.

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.

Chiral acetate enolate equivalent for the synthesis of β-hydroxy acids and esters: X-ray crystal structure of RR,SS-[(η5-C5H5)Fe(CO)(PPh3)(COCH2CH(OH)CH2CH3)]

Abstract The aluminium enolate derived from the iron acetyl complex [(η5-C5H5Fe(CO)(PPh3)COCH3], in contrast to the lithium enolate, undergoes highly stereoselective aldol reactions with aldehydes to generate RR,SS-β-hydroxyacyl complexes which on decomplexation liberate β-hydroxy acids or esters. Determination of the molecular structure of RR,SS-[η5-C5H5)Fe(CO)(PPh3)(COCH2CH(OH)CH2CH3] allowed assignment of the relative configuration of the new chiral centre.

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.

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 synthesis via chiral transition metal auxiliaries

Stoichiometric reagents for the control of the absolute stereochemistry of new chiral centres produced during reactions involving carbon-carbon bond formation are described. Chiral iron acyl reagents act as chiral equivalents of a variety of carbonyl functionalities and their potential for asymmetric synthesis can be illustrated for pseudopeptides, amino acids, P-lactams, y-lactams and lactones. A simple methodology based on arene chromium tricarbonyl chemistry allows the elaboration of benzylic chiral centres with complete control over the absolute stereochemistry. This may be illustrated, for example, by the conversion of amphetamine derivatives into pseudoephedrines.

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]}.

Conformational analysis and x-ray crystal structure of [(η5-C5H5)Fe(CO)(PPh3)CH2CH3]

Abstract The complex [(η5-C5H5)Fe(CO)(PPh3)CH2CH3] is shown by 1H NMR spectroscopy and an X-ray crystal structure analysis to adopt a single conformation with the methyl group residing between the cyclopentadienyl and carbon monoxide ligands.