Craig L. Goodfellow

Stereoselective synthesis of homochiral alpha substituted o-methoxybenzyl alcohols via nucleophilic additions to kinetically resolved homochiral tricarbonyl (η6-o-anisaldehyde)chromium(0).

Abstract Tricarbonyl(η6-o-anisaldehyde)chromium(0) has been kinetically resolved via the selective hydrolysis of one of theL-valinol derived imine presence of deactivated alumina. An X-ray crystal structure analysis on the adduct formed between L-valinol and homochiral (+)-tricarbonyl(η6-o-anisaldehyde)chromium(0) unambiguously established the presence of the corresponding imine and not oxazolidine and confirmed the absolute configuration of the aldehyde complex. Addition of Grignard reagents to homochiral tricarbonyl(η6-o-anisaldehyde)chromium(0) occurs completely stereoselectively to give, following decomplexation, homochiral alpha substituted o-methoxybenzyl alcohols.

Asymmetric synthesis of alpha substituted benzyl alcohols via the stereoselective addition of nucleophiles to homochiral tricarbonyl(η6-o-trialkylsilylbenzaldehyde)chromium(0) complexes

The addition of nucleophiles to tricarbonyl(η6-o-trialkylsilylbenzaldehyde)chromium(0) complexes proceeds with complementary diastereoselectivities in the presence or absence of strong Lewis acids. The ready availability of homochiral aldehyde complexes, via classical resolution with L-valinol, permits the synthesis of alpha substituted benzyl alcohols with high enantiomeric excesses.

Asymmetric synthesis of α-substituted o-methoxybenzyl alcohols via stereoselective additions to kinetically resolved o-anisaldehyde(tricarbonyl)chromium

Homochiral (+)-o-anisaldehyde(tricarbonyl)chromium, prepared by a kinetic resolution procedure involving selective hydrolysis of the diastereoisomeric L-valinol derived imines, undergoes completely stereoselective addition reactions with methyl- and ethyl-magnesium iodide to give enantiomerically pure (–)-(S)-1-(o-methoxyphenyl)ethanol and (–)-(S)-1-(o-methoxyphenyl)propanol.

Stereoselective synthesis of arenechromium tricarbonyl complexes: Origins of the benzylic oxygen directing effects for 1-tetralol derivatives

Abstract Thermolysis of chromium hexacarbonyl with 1-tetralol ( 10 ) or 1-methoxytetralin ( 12 ) yields the corresponding syn -chromium tricarbonyl complexes ( 9 and 11 ) via an oxygen chelation controlled mechanism. Complexation of the t-butyldimethylsilyl protected 1-tetralol ( 14 ) gives a mixture of syn - and anti -diastereoisomers ( 16 and 15 ), with the latter favoured because the steric effect of the O -silyl group outweighs any chelation effect.

Tricarbonylchromium(0) promoted stereoselective transformations of ephedrine and pseudoephedrine derivatives

Abstract (−)-(1 S ,2 S )-( N ,O-Dimethylephedrine)tricarbonyl chromium(0) (6) and (−)-(1 S ,2 R )-( N ,O-dimethylpseudoephedrine)tricarbonylchiromium(0) ( 22 ) undergo completely stereoselective ortho deprotonation upon treatment with alkyllithium base, followed by addition of an electrophile. In both cases, exclusive removal of the pro -( R )- ortho proton was confirmed by single crystal X-ray structure analyses of the methylated products. Addition of methyllithium onto the ortho -formylated derivative of complex ( 6 ) occurs stereoselectively, the stereochemistry of the major product being confirmed by a single crystal X-ray structure determination. The results presented demonstrate an efficient transfer of chirality from a side chain onto the (arene)tricarbonylchromium(0) complex and back to a different side chain.

Asymmetric synthesis of (R)-(+)-a-methyl-o-methoxybenzyl methyl ether via the stereoselective benzylic elaboration of tricarbonyl (η6-o-methoxybenzyl methyl ether)chromium(0)

Abstract Treatment of tricarbonyl(ν6-o-methoxybenzyl methyl ether)chromium(0) with t-butyllithium followed by an electrophile gives a single diastereoisomer of the corresponding alpha substituted complex. The relative configuration within the product from methylation, tricarbonyl(η6-α-methyl-o-methoxybenzyl methyl ether)chromium(0), has been established via a single crystal X-ray structure analysis and found to be (RS,RS), the stereoselectivity thus arising from a non-chelation controlled mechanism. Repetition of the reaction on homochiral (+)-tricarbonyl(η6-o-methoxybenzyl methyl ether)chromium(0) gives, after decomplexation, homochiral (R)-(+)-α-methyl-o-methoxybenzyl methyl ether.

Regioselective nucleophilic additions to tricarbonyl(η6-arene)chromium(0) complexes: electronic versus chelation control

Regioselective addition of t-butyl-lithium to tricarbonyl(η6-benzyl alcohol)chromium(0) proceeds to give tricarbonyl(η6-5-methylene-6-exo-t-butylcyclohexa-1,3-diene)chromium(0), which can be isomerised to tricarbonyl(η6-o-t-butyltoluene)chromium(0). Repetition of the reaction on tricarbonyl(η6-1 -phenethanol)chromium(0) gives regio- and stereo-selectively the corresponding 5-ethylidene complex.

Asymmetric synthesis of R-α-methyl-o-methoxybenzyl methyl ether via the diastereoselective functionalisation of +(−)-(o-methoxybenzyl methyl ether)chromium tricarbonyl

Abstract α-Methylation of (+)-(o-methoxybenzyl methyl ether)Cr(CO)3 occurs completely stereoselectively to yield, after decomplexation, homochiral R-α-methyl-o-methoxybenzyl methyl ether.

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.

Regioselective nucleophilic additions to (η6-benzyl alcohol)tricarbonylchromium: isolation and X-ray crystal structure of the intermediate (η6-5-methylene-6-exo-t-butylcyclohexa-1,3-diene)tricarbonylchromium

Treatment of (η6-benzyl alcohol)tricarbonylchromium with alkyl-lithium compounds (ButLi; MeLi-tetramethylethylenediamine; BunLi; PhLi) regioselectively generates the corresponding η6-5-methylene-6-exo-alkylcyclohexa-1,3-diene complexes which undergo proton catalysed isomerisations to give (η6-ortho-alkyltoluene)tricarbonylchromium complexes.