Manuela Kötteritzsch

O-Silylated steroidal cis-aminoalcohols as chiral auxiliaries: highly diastereoselective Pd-catalyzed cyclopropanation of α,β-unsaturated aldimines

Abstract α,β-Unsaturated imines, obtained from cis -17-silyloxy-16-amino steroids and α,β-unsaturated aldehydes, react with diazomethane in the presence of a catalytic amount of Pd(OAc) 2 with high chemo- and diastereoselectivities to form steroidal cyclopropanocarbaldimines; chromatography on silica gel gives the substituted cyclopropanocarbaldehydes with a high enantiomeric excess and allows recovery of the chiral steroidal auxiliaries.

The Stereoselective Ru3(CO)12-Catalyzed Synthesis of Steroidal 1,3-Dihydropyrrol-2-one Derivatives from α,β-Unsaturated Imines, Carbon Monoxide and Ethylene

The reaction of α,β-unsaturated imines, derived from steroidal amines and cinnamaldehyde, with carbon monoxide and ethylene leads to the formation of steroids with a 1,3-dihydropyrrol-2-one ring system attached to the D-ring of the steroid. In addition, a new stereogenic center at C-3 of the pyrrolone ring is produced during the reaction sequence. In the case of a 16-position of the imine moiety the yields are nearly quantitative but the diastereoselectivity is low whereas the sterically more hindered 17-position shows a decreased reactivity but quite good diastereoselectivities. Complete diastereoselectivity is achieved if the starting compound exhibits an additional silyl ether group in the 17β-position besides the imine subunit in the 16β-position. The compound bearing the pyrrolone substituent at 17β-position was characterized by means of X-ray crystallography showing that the rotation of the pyrrolone ring is hindered by a strong intramolecular hydrogen bond between the carbonyl oxygen of the pyrrolone moiety and the hydrogen at C-17. The question of whether this intramolecular hydrogen bond is also responsible for the observed diastereoselectivities is discussed.

Synthesis of N,N-bis[2-(2-pyridyl)ethyl]amino steroids and related compounds intended as chiral ligands for copper ions

Abstract Compounds with the N , N -bis[2-(2-pyridyl)ethyl]amino structure (RPY2) are useful tridentate ligands for copper(I) ions, which can bind and activate oxygen from the atmosphere. For diastereoselective and enantioselective oxidation reactions, hitherto unknown chiral ligands possessing tripodal structures have been synthesized starting from homochiral steroids. The double Michael addition of primary steroidal amines and aminoalcohols to 2-vinyl pyridine was not very succesful. However, homochiral bidentate ligands with N- [2-(2-pyridyl)ethyl]amino steroid structure could be obtained by this procedure in most cases. New routes (acylation of the bidentate ligands with 2-pyridylacetic acid followed by BH 3 ·THF reduction, or reductive amination of steroidal ketones, acylation and borane reduction) to the desired tridentate RPY2, also at sterically hindered positions, are described. In the last reaction sequence, ‘mixed’ tridentate ligands can also be obtained. Copper complexation and oxygen activation with these ligands are briefly discussed.

Steroid imines as chiral ligands. Diastereoselective formation of (1-azadiene)Fe(CO)3 complexes by sterically tuning the ligand coordination spheres

Abstract The condensation of steroid amines with α,β-unsaturated aldehydes leads to the formation of chiral 1-azadiene ligands with a steroid core attached to nitrogen. If the azadiene chain is situated at the D-ring of the steroid at C 16 or C 17 , respectively, the two diastereotopic faces of the ligand may be discriminated by different neighbouring substituents and their configuration. The reaction of these ligands with Fe 2 (CO) 9 produces mixtures of diastereomeric (1-azadiene)Fe(CO) 3 complexes. By increasing the steric demands of the neighbouring groups it is possible to improve the diastereoselectivity of this complexation reaction from 1:1 mixtures using the least sterically hindered ligands to complete diastereoselectivity using the azadiene derived from cinnamaldehyde and 16β-amino-3-methoxy-estra-1,3,5(10)-triene-17β-ol. In addition, the molecular structure of [17β-(3-phenyl-prop-2-enyliden)-amino-3-methoxy-estra-1,3,5(10)-triene]Fe(CO) 3 was determined by X-ray structure analysis.

Synthesis of cellulose tricarbonates in 1-butyl-3-methylimidazolium chloride/pyridine.

Cellulose phenyl tricarbonates could be synthesized by a novel and fast procedure applying 1-butyl-3-methylimidazolium chloride/pyridine as reaction medium. Even cellulose phenyl carbonates with high degree of substitution are accessible at low molar ratio very efficiently. The reagent phenyl chloroformate is inert in the mixture, which is different from the solvent N,N-dimethylacetamide/LiCl that is usually applied. The products were characterized in detail by two-dimensional NMR- and FTIR-spectroscopy, elemental analysis, and size-exclusion chromatography. This class of cellulose derivatives is a very important intermediate for the design of structures based on cellulose by nucleophilc attack on the carbonyl group.

Addition reactions at the 16(17) double bond of 3-methoxy-13α-estra-1,3,5(10),16-tetraene

The epoxidation, the addition of hypobromous acid, and the hydroboration of 3-methoxy-13alpha-estra-1,3,5(10),16-tetraene 1 with diborane, catecholborane, and 9-BBN were investigated in order to determine the stereochemical outcome and to synthesize new 13alpha-estra-1,3,5(10)-trienes for biological and conformational investigations. It was shown that the sterically demanding reagent 9-BBN participated in a preferred beta attack (53% 16betaOH 10, 34% 17betaOH 8, 13% 16alphaOH 11). This stereochemical result is in agreement with that from another cis addition reaction, the recently described OsO4 dihydroxylation of 1 [Steroids 68 (2003) 113]. With smaller reagents such as B2H6, catecholborane, or magnesium monoperoxyphthalate, a diminished stereoselectivity was observed with only a slight excess of beta attack. The ionic trans addition of hypobromous acid gave two 17-bromo-16-alcohols with 16beta,17alpha (4, 76%) and 16alpha,17beta configuration (5, 24%) formed by trans cleavage of the 16,17alpha- and beta-bromonium ion at position 16. The same regioselective and stereoselective course was found for the cleavage of the 16alpha,17alpha- and 16beta,17beta-epoxides (3 and 2) with hydrazoic acid (3-->16betaN3,17alphaOH 7, 2-->16alphaN3,17betaOH 6). The stereochemistry of the addition reactions to 1 can be explained in terms of a twist-boat conformation involving the C ring of compound 1. From a synthetic viewpoint the synthesis of the beta-epoxide 2 from the bromohydrin 4, the cleavage of this epoxide to 16alpha-substituted-17beta-hydroxy compounds, such as 6, and hydroboration/oxidation with 9-BBN to the hitherto unknown 16beta-hydroxy compound 10 are useful procedures. The bromohydrin 5 is the first 13alpha-steroid with a 17beta-bromo substituent. X-ray analysis revealed twist-boat and 16beta-envelope conformations for rings C and D, respectively.