Formation of chiral 4-chromanones using chiral pyrrolidines in the presence of ureas or thioureas

A process for the manufacturing of compound of formula (I)

• comprising the step of reacting a compound of formula (II-A) and a compound of formula (II-B) in the presence of at least one chiral compound of formula (II-C) and in the presence of at least one urea compound of formula (X-A) or at least one thiourea compound of formula (X-B):
• wherein:
• R1, R3 and R4 are independently from each other hydrogen or methyl groups;
• R2 and R2′ represents hydrogen or a phenol protection group;
• R5 represents either a linear or branched completely saturated C6-25-alkyl group or a linear or branched C6-25-alkyl group comprising at least one carbon-carbon double bond;
• Y1 represents either CH2Y2 or
• wherein
• R6 represents a linear or branched C1-12-alkyl group which optionally further comprises at least one aromatic group and/or C═O and/or NH and/or NH2 group;
• Y2 represents either OH or OR7 or NHR7 or NHCOOR7 or
• and wherein
• R7 represents either
• a linear or branched C1-12-alkyl group which optionally further comprises at least one aromatic group and/or C═O and/or NH and/or NH2 group
• or
• an aryl group or a substituted aryl group or a heteroaryl group or a substituted heteroaryl group, and wherein
• the dotted line represents the a bond by which the corresponding substituent is bound to the rest of formula (II-C);
• and wherein
• the symbol * represents the chiral centre of the chiral isomer of formula (I);
• and
• wherein
• (1) Z1 represents either H or a group CH2Z4;
• Z2 represents either H or a group CH2Z4;
• Z3 represents either H or a group CH2Z4;
• wherein
• Z4 represents H or an C1-C6 alkyl group;
• or wherein
• (2) Z1, Z2 or Z3 is a group of formula (XII):
• wherein
• Z5 is a C1-C6 alkyl group or a CF3 group and n stands for 0, 1, 2 or 3, with the proviso that if Z1 is different from H, that Z2 represents H, and wherein the compound of formula (IIc) is selected from the group consisting of: