Michel Pfau

Enantioselective synthesis of ring-C aromatic steroids by asymmetric Michael-type alkylation of chiral imines.

Abstract Optically active phenanthrones 7 and 12 were prepared, using the asymmetric process involving Michael-type alkylation of chiral imines. Compound 12 was then transformed into the ring-C aromatic steroid 16 .

Enantioselective preparation of key [ABC] intermediates for steroid synthesis through the asymmetric Michael addition process involving chiral imines.

Abstract ( S )-Phenanthrone 7 , prepared from ketone 4 (80 % yield, 93 % ee), was transformed into compounds 8 , 9 , 13 , 15 and 16 , useful intermediates in steroid synthesis.

Diastereoselectivity and enantioselectivity in the addition of chiral imines of 2-methylcyclohexanone to crotonic and methacrylic acid esters

Abstract Additions of the chiral imine (reacting as its secondary enamine tautomer) obtained from ( S )-1-phenylethylamine and 2-methylcyclohexanone were performed with the phenyl ester of crotonic and methacrylic acid as well as with their methyl ester. In each example, the stereochemical relationship of the substituents in the major adduct was shown to be the one predicted in a previous theoretical calculation which established that the reactants complex has a chairlike geometry. In all the examples, the diastereoselectivity is superior to 98%. The enantioselectivity of the reactions is excellent as is usually the case with unsubstituted electrophilic olefins, the example with phenyl methacrylate being particularly remarkable ( de and ee >99%). In each case the favored diastereofacial selectivity is again in accordance with the rule elaborated previously. Relevant facts about the influence of the substituents upon the reactivity, the proportion of regioisomers, the stereoselectivity, and the enantioselectivity of the reaction are given.

Enantioselective synthesis of (+)-α-vetivone through the Michael reaction of chiral imines

Abstract (+)-α-Vetivone has been synthesised in nine steps. The absolute stereochemistry of the two stereogenic centres is controlled in the same key step involving the stereoselective Michael addition of a chiral imine of 4-isopropylidene-2-methylcyclohexanone to phenyl crotonate.

Enantioselective approach to morphinans

Abstract Enantioselective synthesis of morphinan derivative 20 from 2,7-dimethoxynaphthalene has been achieved in twelve steps (11% overall yield).

Enantioselective synthesis of (2S4aS,8aR)-1,1,4a-trimethyldecahydronaphthalen-2-ol [(−)-TMD], (4aS,8aR)-5,5,8a-trimethyloctahydronaphthalen-2(1H)-one, and (−)-polywood®, through michael-type reaction of chiral imines

Abstract The title compounds 6, 15 , and 17 have been synthesized in a straightforward way in good yields and high enantiomeric excesses by the chiral imines method, leading to building-blocks 2 and 10 , followed by a few conventional steps.

Asymmetric intramolecular Ene-reaction

Abstract Asymmetric intramolecular ene reaction of N,N-diallyl iminoamides leas to the formation of optically active spirolactams.

Enantioselective Imine Michael Reaction for the Preparation of the (8'R,8a'S)-8,8a'-Dimethyl-1',3',4',7',8',8a'-hexahydrospiro[1,3-dioxolane-2,2'(6'H)naphthalen]-6'-one Building Block. A formal synthesis of (+)-Valencenol

Abstract The enantioselective Michael addition of a chiral imine of 4-protected 2-methylcyclohexane-1,4-dione to phenyl crotonate led after cyclization to the corresponding bicyclic lactam. Reductive cleavage of the chiral moiety followed by saponification gave the corresponding keto-acid, which was cyclized to afford a lactone. Belleau–Fujimoto reaction of the lactone then led to the title building block (diastereoselectivity 96:4, e.e. >98%) in 11% overall yield from the starting dione. (8 R ,8a S )-(+)-8,8a-Dimethyl-3,4,6,7,8,8a-hexahydronaphthalen-2(1 H )-one was obtained after reduction of the carbonyl group, acetylation, and reductive cleavage–deprotection (52% overall yield), representing a formal synthesis of (+)-valencenol.

Synthesis of 2-methyl-1,3-cyclopentanedione monoethylene ketal

Abstract Direct ketalization of 2-methyl-1,3-cyclopentanedione 3 led to the corresponding diethylene ketal 2 . Carefully controlled hydrolysis of compound 2 afforded the monoethylene ketal 1 in high yield.

Use of α-amino esters as chiral auxiliaries in the enantioselective Michael alkylation of chiral imines

A study concerning the regio- and stereoselectivities of the Michael reaction between chiral imines and electrophilic olefins has been performed with α-amino esters as chiral auxiliaries. In all cases, optically active 1-phenylethylamine, which is usually employed to induce the stereoselectivity in this process, led to higher regio- and stereoselectivities.