Process for the preparation of thietane derivatives

A process for the preparation of a compound of formula IA

• wherein
• A1, A2, A3 and A4 are independently of one another C—H, C—R3, or nitrogen;
• B is O or CH2;
• R1 is C1-C8haloalkyl;
• R2 is aryl or aryl substituted by one to five R4, or heteroaryl or heteroaryl substituted by one to five R4;
• each R3 is independently halogen, cyano, nitro, C1-C8alkyl, C3-C8cycloalkyl, C1-C8haloalkyl, C2-C8alkenyl, C2-C8haloalkenyl, C2-C8alkynyl, C2-C8haloalkynyl, C1-C8alkoxy, C1-C8haloalkoxy, C1-C8alkoxycarbonyl-, amino, hydroxy, mercapto, C1-C8alkylthio, C1-C8haloalkylthio, C1-C8alkylsulfinyl, C1-C8haloalkylsulfinyl, C1-C8alkylsulfonyl, C1-C8haloalkylsulfonyl, C1-C8alkylcarbonyl, or two R3 on adjacent carbon atoms together form a —CH═CH—CH═CH— bridge or a —N═CH—CH═CH— bridge;
• each R4 is independently halogen, cyano, nitro, C1-C8alkyl, C1-C8haloalkyl, C2-C8alkenyl, C2-C8haloalkenyl, C2-C8alkynyl, C2-C8haloalkynyl, hydroxy, C1-C8alkoxy, C1-C8haloalkoxy, mercapto, C1-C8alkylthio, C1-C8haloalkylthio, C1-C8alkylsulfinyl, C1-C8haloalkylsulfinyl, C1-C8alkylsulfonyl, C1-C8haloalkylsulfonyl, C1-C8alkylcarbonyl, C1-C8alkoxycarbonyl, aryl or aryl substituted by one to five R5, or heterocyclyl or heterocyclyl substituted by one to five R5;
• each R5 is independently halogen, cyano, nitro, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy-, or C1-C4haloalkoxy-;
• n is 0, 1 or 2;
• comprising preparing a compound of formula IV
• by either
• a. reacting a compound of formula II
• with a source of cyanide in the presence of water to give a compound of formula III
• b. reducing the compound of formula III with a suitable reducing agent to give a compound of formula IV
• c-i. reacting the compound of formula IV with a compound of formula V
• wherein R is OH, C1-C6alkoxy or Cl, F or Br, and R1, R2, B, A1, A2, A3 and A4 are as defined for compounds of formula IA to give a compound of formula I;
• or
• A) reacting a compound of formula VII
• with CH3NO2 to give a compound of formula XI
• B) reducing the compound of formula XI with a suitable reducing agent to give a compound of formula IV;
• or
• 1) homologating a compound of formula VII
• to give an ester of formula XII
• wherein R is C1-C6alkyl;
• 2) reducing the compound of formula XII using a suitable reducing agent to give a compound of formula XIII
• 3) treating the compound of formula XIII with hydrazoic acid to give a compound of formula IV;
• and
• c-i. reacting the compound of formula IV with a compound of formula V
• wherein R is OH, C1-C6alkoxy or Cl, F or Br, and R1, R2, B, A1, A2, A3 and A4 are as defined for compounds of formula I to give a compound of formula IA;
• or
• c-ii reacting the compound of formula IV with a compound of formula VI
• wherein XB is a leaving group for example a halogen, such as bromo, and R1, R2, B, A1, A2, A3 and A4 are as defined for compounds of formula IA
• with carbon monoxide in the presence of a suitable catalyst to give a compound of formula IA;
• and wherein the method optionally comprises oxidizing the sulfur atom of the thietane moiety.