Processes for preparing functionalized cyclooctenes

A process of preparing a compound of formula I, or a salt thereof:

• wherein
• R1 is selected from the group consisting of —OR4, optionally substituted heterocyclyl, and an amino acid moiety;
• n is 0, 1, 2, 3, or 4;
• each R2 is independently C1-4alkyl, C1-4haloalkyl, and C1-4alkoxy;
• D is a payload moiety;
• and
• R4 is hydrogen or C1-4alkyl;
• comprising contacting a compound of formula II:
• with HO—R4, an optionally substituted heterocycle, or an amino acid moiety, or a salt thereof, and N,O-bis(trimethylsilyl)acetamide
• in an organic solvent in the presence of a base;
• wherein the amino acid moiety is selected from the group consisting of a natural amino acid, an unnatural amino acid, —NR1c—C1-4alkylene-optionally substituted heterocyclyl, —NR1c—C1-4alkylene-N(R1d)2, —N(R1c)CHR1eCO2H, —N(R1c)—C1-6alkylene-CO2H, —N(R1f)—C2-4alkylene-(N(C1-4alkylene-CO2H)—C2-4alkylene)m-N(C1-4alkylene-CO2H)2, —N(R1e)CHR1eC(O)OC1-6alkyl, —N(R1c)—C1-6alkylene-C(O)O—C1-6alkyl, and —N(R1f)—C2-4alkylene-(N(C1-4alkylene-C(O)OC1-6alkyl)-C2-4alkylene)m-N(C1-4alkylene-C(O)OC1-6alkyl)2;
• wherein
• R1c and R1d are each independently hydrogen or C1-4alkyl;
• R1e is —C1-4alkylene-CO2H, —C1-4alkylene-CONH2, or —C1-4alkylene-OH;
• R1f is hydrogen, —C1-6alkyl, or —C1-4alkylene-CO2H;
• and
• m is 0, 1, 2, or 3.