Regioselective halogenation of nicotine and substituted nicotines

A method of making a compound of Formula Ib:

• wherein
• R4 and R5 are H, alkyl or aryl, or R4 is —SiR20R21R22, wherein R20, R21 and R22 are each independently alkyl or ary;
• R6 is H, alkyl, aryl, alkoxy or halo;
• R7 is H, alkyl or aryl;
• and
• X is halo;
• comprising the steps of:
• (a) metalating a compound of Formula II:
• wherein R2 is H, with a metal base in the presence of a compound of the formula XSnR30R31R32, wherein X is halo and R30, R31 and R32 are each alkyl or aryl, to form an organometallic intermediate compound of Formula III:
• and then
• (b) reacting said organometallic intermediate compound of Formula III with a halogenating agent to produce a compound of Formula Ib.

A compound of Formula III:

• wherein:
• R4 and R5 are H, alkyl or aryl, or R4 is —SiR20R21R22, wherein R20, R21 and R22 are each independently alkyl or ary;
• R6 is H, alkyl, aryl, alkoxy or halo;
• R7 is H, alkyl or aryl;
• and
• R30, R31 and R32 are each alkyl or aryl.