Kjell Undheim

RUTHENIUM(II) IN RING CLOSING METATHESIS FOR THE STEREOSELECTIVE PREPARATION OF CYCLIC 1-AMINO-1-CARBOXYLIC ACIDS

Abstract Stereoselective synthesis of α-amino acids where the α-carbon of the amino acid is incorporated into a five-, six- or seven-membered ring is described. The stereoselective control results from stepwise bisalkenylation of (R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine. Ring closing metathesis was effected by ruthenium(II)-catalysis. The spiro-cycloalkene intermediates were further transformed into 1-aminocycloalkene-1-carboxylic acid derivatives by mild acid hydrolysis.

Stannylation reaction and cross-couplings in pyrimidines

Abstract Pyrimidines have been stannylated in the activated 4-position by thermal decar☐ylation of the corresponding car☐ylic organotin esters. The decar☐ylation can be catalyzed by bis(acetonitrile)palladium(II) dichloride. 4-Iodopyrimidines are 4-stannylated either by substitution reactions with tri-n-butyltin-copper or by coupling reaction with hexamethyl- or hexa-n-butyl-ditin and Pd(II) catalysis. The stannylated pyrimidines form new carbon-carbon bonds by Pd(II)-catalyzed cross-couplings, tert-Butyldimethylsilyl-, dimethylthexylsilyl- and tert-butyldiphenylsilyl-oxymethyl (tri-n-butyl)tin have been synthesized and used in Pd(II)-catalyzed cross-coupling reactions with 4-chloropyrimidines. The silyi groups were not cleaved off during exposure to fluoride ions in aqueous media but were readily removed by fluoride ions in THF to yield the 4-hydroxymethylpyrimidine.

Synthesis of conformationally restricted serine derivatives through ruthenium(II)-catalyzed ring closing metathesis

Abstract Stereoselective synthesis of α-amino-β-hydroxy acids where the α-carbon of the amino acid is incorporated into a five-, six- or seven-membered ring is described. The stereoselective control at the chiral auxiliary carbon results from stepwise alkenylation and aldol formation using metalated species of the chiral auxiliary ( R )-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine. Ring closing metathesis was effected by ruthenium(II)-catalysis. The spiro-cycloalkene intermediates were transformed into 1-amino-2-hydroxycycloalkene-1-carboxylic acid derivatives by mild acid hydrolysis.

RUTHENIUM-CATALYZED ENYNE METATHESIS IN STEREOSELECTIVE PREPARATION OF CYCLIC 1-AMINO-1-CARBOXYLIC ACIDS

Abstract Stereoselective syntheses of α-amino acids are described. The α-carbon of the amino acid is incorporated into a five- or six-membered ring which is a conjugated diene with one exocyclic double bond. Enynes were intermediates for the metathesis cyclization reaction effected by ruthenium(II)-catalysis. The enyne substrates were available in stereochemically pure form by stepwise alkylations of the chiral auxiliary ( R )-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine with bromo-alkenes and -alkynes.

Stannylation in the electrophilic 2- and 4/6-pyrimidine position and the use of stannylpyrimidines in coupling and tin-lithium exchange reactions

Abstract 2-Stannylpyrimidines have been prepared by stannyl anion substitution in 2-chloropyrimidines. Stannylation in the 4-position was via the iodo-derivative or via the 4-lithio derivative and lithium-tin transmetallation. Tin-lithium exchange in the 2-position resulted in 2-lithiopyrimidine. Ketones were formed from the stannylpyrimidines and acid chlorides, aryl bromides required Pd-catalysis for coupling reaction.

High temperature microwave-accelerated ruthenium-catalysed domino RCM reactions

The thermal instability of ruthenium(II)-catalyst systems under prolonged heating at 88°C in RCM reactions of dienyne and triyne substrates has been circumvented by a microwave temperature increase to 160°C when the reaction times were reduced to minutes.

Ru(II)-Catalyzed Ring Closing Metathesis in Stereoselective Spiroannulations and Cascade Reactions of Cyclic Dipeptide Substrates

Abstract Several Ru(II)-catalyzed ring closing metathesis (RCM) reactions have been reviewed where the substrates were diene or enyne geminally disubstituted cyclic dipeptide derivatives. The RCM reactions are highly useful for the preparation of spiroannulated cyclic dipeptides as precursors for conformationally restricted cyclic α-amino acid derivatives. Five-, six- and seven-membered rings can be formed. Six- and seven-membered rings were formed most readily from dienes, five- and six-membered rings from enynes. Cascade reactions of diene substrates, which were connected by an alkynyl bridge between the two cyclic dipeptide units, yielded bis(cyclic α-amino acid) as precursors for cystine analogues.

Pd(0)-catalyzed allylic alkylation in the synthesis of (±)carbovir.

Abstract Racemic carbovir 1 has been synthesized in 6 steps from the cyclopentanone 8 with a Pd(0)-catalyzed allylation as a key reaction.

Ru(II)-catalyzed RCM reactions with electrophilic diene substrates

Abstract Electrophilic dienes from α,β-unsaturated ketones readily undergo the Ru(II)-benzylidene initiated RCM reaction. Cyclohexenone spirane formation was faster than cycloheptenone spirane formation. The products were pure stereoisomers. The products after hydrolysis were α,β-unsaturated oxo derivatives of cyclic α-amino acids.

Hydroxymethylated cyclic α-amino acid dipeptides by ruthenium ring closing metathesis

Abstract Stereoselective syntheses of cyclic α-amino-β-hydroxymethylcyclohexene-α-carboxylic acids are described. The acids were isolated as dipeptides. RCM reactions were effected by Ru(II)-catalysis on hydroxymethylated dienes. The diene substrates were available in stereochemically pure form by stepwise alkylations of ( R )-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine with 4-bromo-1-butene and vinyloxirane.