Continuous carbonylation processes

A process for continuous carbonylation of an epoxide or lactone feedstock, comprising:

• continuously reacting an epoxide or lactone feedstock with carbon monoxide in the presence of a catalyst in a carbonylation reaction vessel, wherein the catalyst comprises a Lewis acid and a metal carbonyl;
• and
• continuously or intermittently introducing to the carbonylation reaction vessel a catalyst replacement component which is different from the carbonylation catalyst, wherein the catalyst replacement component comprises a species selected from the group consisting of the Lewis acid, a precursor to the Lewis acid, the metal carbonyl, and a precursor to the metal carbonyl,
• wherein the precursor to the metal carbonyl is a neutral metal carbonyl complex, and
• wherein the precursor to the Lewis acid is:
• wherein:
• each Rq is independently C1-12 aliphatic or aryl,
• wherein the aryl is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen;
• —(CH2)0-4R∘;
• —(CH2)0-4OR∘;
• —O—(CH2)0-4C(O)OR∘;
• —(CH2)0-4 CH(OR∘)2;
• —(CH2)0-4SR∘;
• —(CH2)0-4Ph;
• —(CH2)0-4O(CH2)0-1Ph;
• —CH═CHPh;
• —NO2;
• —CN;
• —N3;
• —(CH2)0-4N(R∘)2;
• —(CH2)0-4N(R∘C(O)R∘;
• —N(R∘C(S)R∘;
• —(CH2)0-4N(R∘)C(O)NR∘2;
• —N(R∘)C(S)NR∘2;
• —(CH2)0-4N(R∘)C(O)OR∘;
• —N(R∘)N(R∘)C(O)R∘;
• —N(R∘)N(R∘)C(O)NR∘2;
• —N(R∘)N(R∘)C(O)OR∘;
• —(CH2)0-4C(O)R∘;
• —C(S)R∘;
• —(CH2)0-4C(O)OR∘;
• —(CH2)0-4C(O)N(R∘)2;
• —(CH2)0-4C(O)SR∘;
• —(CH2)0-4C(O)OSiR∘3;
• —(CH2)0-4OC(O)R∘;
• —OC(O)(CH2)0-4SR∘;
• —SC(S)SR∘;
• —(CH2)0-4SC(O)R∘;
• —(CH2)0-4C(O)NR∘2;
• —C(S)NR∘2;
• —C(S)SR∘, —SC(S)SR∘;
• —(CH2)0-4OC(O)NR∘2;
• —C(O)N(OR∘)R∘, —C(O)C(O)R∘, —C(O)CH2C(O)R∘;
• —C(NOR∘)R∘;
• —(CH2)0-4SSR∘;
• —(CH2)0-4S(O)2R∘;
• —(CH2)0-4S(O)2OR∘;
• —(CH2)0-4OS(O)2R∘;
• —S(O)2NR∘2;
• —(CH2)0-4S(O)R∘;
• —N(R∘)S(O)2NR∘2;
• —N(R∘)S(O)2R∘;
• —N(OR∘)R∘;
• —C(NH)NR∘2;
• —P(O)2R∘;
• —P(O)R∘2;
• —OP(O)R∘2;
• —OP(O)(OR∘)2;
• SiR∘3;
• —(C1-4 straight or branched alkylene)O—N(R∘)2;
• and —(C1-4 straight or branched alkylene)C(O)O—N(R∘)2,
• wherein R∘at each occurrence is
• independently hydrogen, C1-8 aliphatic, —CH2Ph or —O(CH2)0-1Ph;
• or
• a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• wherein two independent occurrences of R∘, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or polycyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• M is a metal atom;
• Rd at each occurrence is
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein two or more Rd groups may be taken together to form one or more optionally substituted rings;
• each Ry is
• independently hydrogen;
• or an optionally substituted group selected the group consisting of:
• acyl;
• carbamoyl,
• arylalkyl;
• 6- to 10-membered aryl;
• C1-12 aliphatic;
• C1-12 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• an oxygen protecting group;
• and
• a nitrogen protecting group;
• or
• wherein two Ry on the same nitrogen atom are taken with the nitrogen atom to form an optionally substituted 4- to 7-membered heterocyclic ring having 0-2 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• and
• each R4 is independently a hydroxyl protecting group or Ry;
• R1a, R1a′, R2a, R2a′, R3a, and R3a′ are
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein any of (R2a′ and R3′), (R2a and R3a), (R1a and R2a), and (R1a′ and R2′) may optionally be taken together with the carbon atoms to which they are attached to form one or more rings which may in turn be substituted with one or more Ry groups;
• and
• R4a is selected from the group consisting of:
• wherein:
• Rc at each occurrence is
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein two or more Rc groups may be taken together with the carbon atoms to which they are attached and any intervening atoms to form one or more rings;
• or
• wherein two Rc groups are attached to the same carbon atom, they may be taken together along with the carbon atom to which they are attached to form a moiety selected from the group consisting of:
• a 3- to 8-membered spirocyclic ring, a carbonyl, an oxime, a hydrazone, an imine;
• and an optionally substituted alkene;
• Y is a divalent linker selected from the group consisting of:
• —NRy—, —N(Ry)C(O)—, —C(O)NRy—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —C(═S)—, —C(═NRy)—, —N═N—;
• a polyether;
• a C3 to C8 substituted or unsubstituted carbocycle;
• and a C1 to C8 substituted or unsubstituted heterocycle;
• m′ is 0 or an integer from 1 to 4, inclusive;
• and
• q is 0 or an integer from 1 to 4, inclusive.

A process for continuous carbonylation of an epoxide or lactone feedstock, comprising:

• continuously reacting an epoxide or lactone feedstock with carbon monoxide in the presence of a carbonylation catalyst in a carbonylation reaction vessel to produce a carbonylation product stream,
• wherein the carbonylation catalyst comprises a Lewis acid and a metal carbonyl,
• wherein the carbonylation product stream comprises at least one carbonylation product, at least some of the Lewis acid and at least some of the metal carbonyl, and
• wherein at a start time of the process, the carbonylation reaction vessel contains an initial concentration of the Lewis acid and an initial concentration of the metal carbonyl;
• separating the carbonylation product stream from the carbonylation reaction vessel by a nanofiltration membrane,
• wherein the nanofiltration membrane retains at least a portion of the Lewis acid and at least a portion of the metal carbonyl, and permeates at least one carbonylation product;
• and
• adding to the carbonylation reaction vessel, at a time after the start time of the process, a catalyst replacement component which is different from the carbonylation catalyst,
• wherein the catalyst replacement component is added at a rate or time of addition based on a rate of depletion of one or both of the Lewis acid and the metal carbonyl in the carbonylation reaction vessel,
• wherein the catalyst replacement component comprises the Lewis acid, a precursor to the Lewis acid, the metal carbonyl, and a precursor to the metal carbonyl,
• wherein the precursor to the metal carbonyl is a neutral metal carbonyl complex, and
• wherein the precursor to the Lewis acid is:
• wherein:
• each Rq is independently C1-12 aliphatic or aryl,
• wherein the aryl is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen;
• —(CH2)0-4R∘;
• —(CH2)0-4OR∘;
• —O—(CH2)0-4C(O)OR∘;
• —(CH2)0-4 CH(OR∘)2;
• —(CH2)0-4SR∘;
• —(CH2)0-4Ph;
• —(CH2)0-4O(CH2)0-1Ph;
• —CH═CHPh;
• —NO2;
• —CN;
• —N3;
• —(CH2)0-4N(R∘)2;
• —(CH2)0-4N(R∘C(O)R∘;
• —N(R∘C(S)R∘;
• —(CH2)0-4N(R∘)C(O)NR∘2;
• —N(R∘)C(S)NR∘2;
• —(CH2)0-4N(R∘)C(O)OR∘;
• —N(R∘)N(R∘)C(O)R∘;
• —N(R∘)N(R∘)C(O)NR∘2;
• —N(R∘)N(R∘)C(O)OR∘;
• —(CH2)0-4C(O)R∘;
• —C(S)R∘;
• —(CH2)0-4C(O)OR∘;
• —(CH2)0-4C(O)N(R∘)2;
• —(CH2)0-4C(O)SR∘;
• —(CH2)0-4C(O)OSiR∘3;
• —(CH2)0-4OC(O)R∘;
• —OC(O)(CH2)0-4SR∘;
• —SC(S)SR∘;
• —(CH2)0-4SC(O)R∘;
• —(CH2)0-4C(O)NR∘2;
• —C(S)NR∘2;
• —C(S)SR∘, —SC(S)SR∘;
• —(CH2)0-4OC(O)NR∘2;
• —C(O)N(OR∘)R∘, —C(O)C(O)R∘, —C(O)CH2C(O)R∘;
• —C(NOR∘)R∘;
• —(CH2)0-4SSR∘;
• —(CH2)0-4S(O)2R∘;
• —(CH2)0-4S(O)2OR∘;
• —(CH2)0-4OS(O)2R∘;
• —S(O)2NR∘2;
• —(CH2)0-4S(O)R∘;
• —N(R∘)S(O)2NR∘2;
• —N(R∘)S(O)2R∘;
• —N(OR∘)R∘;
• —C(NH)NR∘2;
• —P(O)2R∘;
• —P(O)R∘2;
• —OP(O)R∘2;
• —OP(O)(OR∘)2;
• SiR∘3;
• —(C1-4 straight or branched alkylene)O—N(R∘)2;
• and —(C1-4 straight or branched alkylene)C(O)O—N(R∘)2,
• wherein R∘at each occurrence is
• independently hydrogen, C1-8 aliphatic, —CH2Ph, or —O(CH2)0-1Ph;
• or
• a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• or
• wherein two independent occurrences of R∘, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or polycyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• M is a metal atom;
• Rd at each occurrence is
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein two or more Rd groups may be taken together to form one or more optionally substituted rings;
• each Ry is
• independently hydrogen;
• or an optionally substituted group selected the group consisting of:
• acyl;
• carbamoyl,
• arylalkyl;
• 6- to 10-membered aryl;
• C1-12 aliphatic;
• C1-12 heteroaliphatic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• an oxygen protecting group;
• and
• a nitrogen protecting group;
• or
• wherein two Ry on the same nitrogen atom are taken with the nitrogen atom to form an optionally substituted 4- to 7-membered heterocyclic ring having 0-2 additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• and
• each R4 is independently a hydroxyl protecting group or Ry;
• R1a, R1a′, R2a, R2a′, R3a, and R3a′ are
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein any of (R2a′ and R3′), (R2a and R3a), (R1a and R2a), and (R1a′ and R2′) may optionally be taken together with the carbon atoms to which they are attached to form one or more rings which may in turn be substituted with one or more Ry groups;
• and
• R4a is selected from the group consisting of:
• wherein:
• Rc at each occurrence is
• independently hydrogen, halogen, —OR4, —NRy2, —SRy, —CN, —NO2, —SO2Ry, —SORy, —SO2NRy2;
• —CNO, —NRySO2Ry, —NCO, —N3, or —SiRy3;
• or an optionally substituted group selected from the group consisting of:
• C1-20 aliphatic;
• C1-20 heteroaliphatic having 1-4 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• 6- to 10-membered aryl;
• 5- to 10-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• 4- to 7-membered heterocyclic having 1-2 heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or
• wherein two or more Rc groups may be taken together with the carbon atoms to which they are attached and any intervening atoms to form one or more rings;
• or
• wherein two Rc groups are attached to the same carbon atom, they may be taken together along with the carbon atom to which they are attached to form a moiety selected from the group consisting of:
• a 3- to 8-membered spirocyclic ring, a carbonyl, an oxime, a hydrazone, an imine;
• and an optionally substituted alkene;
• Y is a divalent linker selected from the group consisting of:
• —NRy—, —N(Ry)C(O)—, —C(O)NRy—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —C(═S)—, —C(═NRy)—, —N═N—;
• a polyether;
• a C3 to C8 substituted or unsubstituted carbocycle;
• and a C1 to C8 substituted or unsubstituted heterocycle;
• m′ is 0 or an integer from 1 to 4, inclusive;
• and
• q is 0 or an integer from 1 to 4, inclusive.