Ring opening metathesis of alkenes

A compound represented by the formula (Formula Ia):

• 27
• in which
• W is CH2 or O;
• Z is CHC(O)R8 or NR5;
• R5 is hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• R6 and R7 taken together are O, or R6 is CHC(O)R′8 and R7 is hydrogen;
• R8 and R′8 are each independently hydroxy, alkoxy, aryloxy, or amino;
• and
• one of R9 and R10 is hydrogen and the other of R9 and R10 is alkyl or aryl;
• or a salt thereof.

A compound represented by the formula (Formula II):

• 28
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Q is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• Ra and Rb are each hydrogen, or Ra and Rb taken together are O;
• or a salt thereof.

A method for preparing a compound represented by the formula (Formula I):

• 29
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Y is a moiety selected from the group consisting of O, S, NR5, and CR1R2Q;
• Q is independently for each occurrence a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• or a first occurrence of R1 or R2, taken together with a second occurrence of R1 or R2, and the carbon atoms to which they are attached, form a carbocyclic or heterocyclic ring;
• or at least one of R1, R2, R′1, R′2, or R5 is a linker group to a solid support;
• or a salt thereof;
• the method comprising the step of reacting a bicyclic alkene represented by the formula (Formula III):
• 30
• with a compound represented by the formula (Formula IV):
• 31
• under ring opening cross-metathesis conditions, such that a compound of Formula I is prepared.

A method for preparing a compound represented by the formula (Formula II):

• 32
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Q is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• Ra and Rb are each hydrogen, or Ra and Rb taken together are O;
• or a salt thereof;
• the method comprising the steps of:
• reacting a compound represented by the formula (Formula V):
• 33
• in which
• X, R1, R2, R5, Ra and Rb are as defined above;
• and P is hydrogen or a protecting group;
• with a compound represented by the formula (Formula IV):
• 34
• in which
• R3 and R4 are as defined above;
• under ring opening cross-metathesis conditions, such that a cross-metathesis product is prepared;
• and
• cyclizing the cross-metathesis product, such that a compound of Formula II is prepared.

A library of compounds represented by the formula (Formula I):

• 35
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Y is a moiety selected from the group consisting of O, S, NR5, and CR1R2Q;
• Q is independently for each occurrence a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• or a first occurrence of R1 or R2, taken together with a second occurrence of R1 or R2, and the carbon atoms to which they are attached, form a carbocyclic or heterocyclic ring;
• or at least one of R1, R2, R′1, R′2, or R5 is a linker group to a solid support;
• or a salt thereof.

A library of compounds represented by the formula (Formula II):

• 36
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Q is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• Ra and Rb are each hydrogen, or Ra and Rb taken together are O;
• or a salt thereof.

A method for preparing a library of compounds represented by the formula (Formula I):

• 37
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Y is a moiety selected from the group consisting of O, S, NR5, and CR1R2Q;
• Q is independently for each occurrence a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• or a first occurrence of R1 or R2, taken together with a second occurrence of R1 or R2, and the carbon atoms to which they are attached, form a carbocyclic or heterocyclic ring;
• or at least one of R1, R2, R′1, R′2, or R5 is a linker group;
• or a salt thereof;
• the method comprising the steps of reacting a bicyclic alkene represented by the formula (Formula III):
• 38
• with a compound represented by the formula (Formula IV):
• 39
• under ring opening cross-metathesis conditions, such that a library of compounds of Formula I is prepared;
• wherein at least one of the bicyclic alkene and the olefin is provided as a variegated population.

A method for preparing a library of compounds represented by the formula (Formula II):

• 40
• in which
• X is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR′1R′2Q;
• Q is a direct bond or a moiety selected from the group consisting of O, S, NR5, and CR1R2;
• R1 and R2 are each independently for each occurrence hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R′1 and R′2 are each independently hydrogen, halogen, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, heterocyclyl, amino, acylamino, hydroxy, alkoxy, aryloxy, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aminocarbonyloxy, or alkylthio;
• or R1 and R2 taken together are O or S;
• R3 and R4 are each independently hydrogen, halogen, cyano, nitro, boronato, stannyl, silyl, or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocyclyl, carboxy, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, or aminocarbonyloxy;
• R5 is independently for each occurrence hydrogen or substituted or unsubstituted alkyl, alkenyl, alkynyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl or heterocyclyl;
• Ra and Rb are each hydrogen, or Ra and Rb taken together are O;
• or a salt thereof;
• the method comprising the steps of:
• reacting a compound represented by the formula (Formula V):
• 41
• in which
• X, R1, R2, R5, Ra and Rb are as defined above;
• and P is hydrogen or a protecting group;
• with a compound represented by the formula (Formula IV):
• 42
• in which
• R3 and R4 are as defined above;
• under ring opening cross-metathesis conditions, such that a cross-metathesis product is prepared;
• and
• cyclizing the cross-metathesis product, such that a compound of Formula II is prepared;
• wherein at least one of the compounds of Formula V and Formula IV is provided as a variegated population.