Continuous carbonylation processes
Provided are processes for monitoring and maintaining continuous carbonylation of epoxides or lactones. Processes include measuring parameters affecting the rate of the carbonylation reaction and adding supplemental replacement catalyst replacement components to maintain a constant rate of carbonylation.
1. 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,
wherein the carbonylation catalyst comprises a Lewis acid and a 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; 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 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 R q is independently C 1-12 aliphatic or aryl,
wherein the aryl is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen; —(CH 2 ) 0-4 R ∘ ; —(CH 2 ) 0-4 OR ∘ ; —O—(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 CH(OR ∘ ) 2 ; —(CH 2 ) 0-4 SR ∘ ; —(CH 2 ) 0-4 Ph; —(CH 2 ) 0-4 O(CH 2 ) 0-1 Ph; —CH═CHPh; —NO 2 ; —CN; —N 3 ; —(CH 2 ) 0-4 N(R ∘ ) 2 ; —(CH 2 ) 0-4 N(R ∘ C(O)R ∘ ; —N(R ∘ C(S)R ∘ ; —(CH 2 ) 0-4 N(R ∘ )C(O)NR ∘ 2 ; —N(R ∘ )C(S)NR ∘ 2 ; —(CH 2 ) 0-4 N(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 ∘ ; —(CH 2 ) 0-4 C(O)R ∘ ; —C(S)R ∘ ; —(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 C(O)N(R ∘ ) 2 ; —(CH 2 ) 0-4 C(O)SR ∘ ; —(CH 2 ) 0-4 C(O)OSiR ∘ 3 ; —(CH 2 ) 0-4 OC(O)R ∘ ; —OC(O)(CH 2 ) 0-4 SR ∘ ; —SC(S)SR ∘ ; —(CH 2 ) 0-4 SC(O)R ∘ ; —(CH 2 ) 0-4 C(O)NR ∘ 2 ; —C(S)NR ∘ 2 ; —C(S)SR ∘ , —SC(S)SR ∘ ; —(CH 2 ) 0-4 OC(O)NR ∘ 2 ; —C(O)N(OR ∘ )R ∘ , —C(O)C(O)R ∘ , —C(O)CH 2 C(O)R ∘ ; —C(NOR ∘ )R ∘ ; —(CH 2 ) 0-4 SSR ∘ ; —(CH 2 ) 0-4 S(O) 2 R ∘ ; —(CH 2 ) 0-4 S(O) 2 OR ∘ ; —(CH 2 ) 0-4 OS(O) 2 R ∘ ; —S(O) 2 NR ∘ 2 ; —(CH 2 ) 0-4 S(O)R ∘ ; —N(R ∘ )S(O) 2 NR ∘ 2 ; —N(R ∘ )S(O) 2 R ∘ ; —N(OR ∘ )R ∘ ; —C(NH)NR ∘ 2 ; —P(O) 2 R ∘ ; —P(O)R ∘ 2 ; —OP(O)R ∘ 2 ; —OP(O)(OR ∘ ) 2 ; SiR ∘ 3 ; —(C 1-4 straight or branched alkylene)O—N(R ∘ ) 2 ; and —(C 1-4 straight or branched alkylene)C(O)O—N(R ∘ ) 2 ,
wherein R ∘ at each occurrence is
independently hydrogen, C 1-8 aliphatic, —CH 2 Ph, or —O(CH 2 ) 0-1 Ph; 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;
R d at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R d groups may be taken together to form one or more optionally substituted rings;
each R y is
independently hydrogen; or an optionally substituted group selected the group consisting of:
acyl;
carbamoyl,
arylalkyl;
6- to 10-membered aryl;
C 1-12 aliphatic;
C 1-12 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 R y 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 R 4 is independently a hydroxyl protecting group or R y ;
R 1a , R 1a′ , R 2a , R 2a′ , R 3a , and R 3a′ are
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 (R 2a′ and R 3′ ), (R 2a and R 3a ), (R 1a and R 2a ), and (R 1a′ and R 2′ ) 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 R y groups; and
R 4a is selected from the group consisting of:
wherein:
R c at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R c 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 R c 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: —NR y —, —N(R y )C(O)—, —C(O)NR y —, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR y )—, —N═N—; a polyether; a C 3 to C 8 substituted or unsubstituted carbocycle; and a C 1 to C 8 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.
2. The process of claim 1 , wherein a rate or time of addition of the catalyst replacement component is based on a rate of depletion of one or both of the Lewis acid and the metal carbonyl in the carbonylation reaction vessel.
3. The process of claim 2 , wherein one or both of the Lewis acid and the metal carbonyl of the carbonylation catalyst depletes over time in the carbonylation reaction vessel, and the method further comprises determining the depletion,
wherein the depletion of one or both of the Lewis acid and the metal carbonyl in the carbonylation reaction vessel is determined by:
measuring one or more parameters selected from the group consisting of:
i-a) a concentration of the Lewis acid in the carbonylation reaction vessel;
i-b) a concentration of a decomposition product of the Lewis acid in the carbonylation reaction vessel;
ii-a) a concentration of the Lewis acid in a process stream downstream from the carbonylation reaction vessel;
ii-b) a concentration of a decomposition product of the Lewis acid in a process stream downstream from the carbonylation reaction vessel;
iii-a) a concentration of the metal carbonyl in the carbonylation reaction vessel;
iii-b) a concentration of a decomposition product of the metal carbonyl in the carbonylation reaction vessel;
iv-a) a concentration of the metal carbonyl in a process stream downstream from the carbonylation reaction vessel;
iv-b) a concentration of a decomposition product of the metal carbonyl in a process stream downstream from the carbonylation reaction vessel; and
v) a rate of the carbonylation reaction; and
obtaining a measured value of the one or more parameters.
4. The process of claim 3 , further comprising:
comparing the measured value of the one or more parameters to a predetermined reference value for each parameter; and
determining a rate of addition or a time of addition of the catalyst replacement component based on the comparison.
5. The process of claim 4 , wherein:
the rate of addition of the metal carbonyl or a precursor to the metal carbonyl is increased when the value of a measurement in parameter iii-b, iv-a, or iv-b, or any combination thereof, is greater than the predetermined value for each parameter;
the rate of addition of the metal carbonyl or a precursor to the metal carbonyl is increased when the value of a measurement in parameter iii-a is less than the predetermined value for the parameter;
the rate of addition of the Lewis acid or a precursor to the Lewis Acid is increased when the value of a measurement in parameter i-b, ii-a, or ii-b, or any combination thereof, is greater than the predetermined value for each parameter; and
the rate of addition of the Lewis acid or a precursor to the Lewis acid is increased when the value of a measurement in parameter i-a is less than the predetermined value for the parameter.
6. The process of claim 1 , wherein the reacting of the epoxide or lactone feedstock with the carbon monoxide in the presence of the carbonylation catalyst in the carbonylation reaction vessel produces carbonylation products in a carbonylation product stream, and
the process further comprises separating the carbonylation product stream from the carbonylation reaction vessel.
7. The process of claim 6 , wherein the carbonylation product stream is separated from the carbonylation reaction vessel by a nanofiltration membrane, and wherein the nanofiltration membrane retains at least a portion of the Lewis acid and the metal carbonyl, and permeates the carbonylation products.
8. The process of claim 1 , wherein the precursor to the metal carbonyl is Co 2 (CO) 8 or Co 4 (CO) 12 .
9. The process of claim 1 , wherein the catalyst replacement component is added directly to the carbonylation reaction vessel.
10. The process of claim 1 , wherein the catalyst replacement component is recycled from a carbonylation product stream, an intermediate carbonylation process stream, or a process stream downstream of the carbonylation reaction vessel.
11. The process of claim 3 , wherein the one or more parameters are measured continuously.
12. The process of claim 1 , wherein the catalyst replacement component is added continuously.
13. The process of claim 1 , wherein the catalyst replacement component is added intermittently.
14. 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 R q is independently C 1-12 aliphatic or aryl,
wherein the aryl is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen; —(CH 2 ) 0-4 R ∘ ; —(CH 2 ) 0-4 OR ∘ ; —O—(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 CH(OR ∘ ) 2 ; —(CH 2 ) 0-4 SR ∘ ; —(CH 2 ) 0-4 Ph; —(CH 2 ) 0-4 O(CH 2 ) 0-1 Ph; —CH═CHPh; —NO 2 ; —CN; —N 3 ; —(CH 2 ) 0-4 N(R ∘ ) 2 ; —(CH 2 ) 0-4 N(R ∘ C(O)R ∘ ; —N(R ∘ C(S)R ∘ ; —(CH 2 ) 0-4 N(R ∘ )C(O)NR ∘ 2 ; —N(R ∘ )C(S)NR ∘ 2 ; —(CH 2 ) 0-4 N(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 ∘ ; —(CH 2 ) 0-4 C(O)R ∘ ; —C(S)R ∘ ; —(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 C(O)N(R ∘ ) 2 ; —(CH 2 ) 0-4 C(O)SR ∘ ; —(CH 2 ) 0-4 C(O)OSiR ∘ 3 ; —(CH 2 ) 0-4 OC(O)R ∘ ; —OC(O)(CH 2 ) 0-4 SR ∘ ; —SC(S)SR ∘ ; —(CH 2 ) 0-4 SC(O)R ∘ ; —(CH 2 ) 0-4 C(O)NR ∘ 2 ; —C(S)NR ∘ 2 ; —C(S)SR ∘ , —SC(S)SR ∘ ; —(CH 2 ) 0-4 OC(O)NR ∘ 2 ; —C(O)N(OR ∘ )R ∘ , —C(O)C(O)R ∘ , —C(O)CH 2 C(O)R ∘ ; —C(NOR ∘ )R ∘ ; —(CH 2 ) 0-4 SSR ∘ ; —(CH 2 ) 0-4 S(O) 2 R ∘ ; —(CH 2 ) 0-4 S(O) 2 OR ∘ ; —(CH 2 ) 0-4 OS(O) 2 R ∘ ; —S(O) 2 NR ∘ 2 ; —(CH 2 ) 0-4 S(O)R ∘ ; —N(R ∘ )S(O) 2 NR ∘ 2 ; —N(R ∘ )S(O) 2 R ∘ ; —N(OR ∘ )R ∘ ; —C(NH)NR ∘ 2 ; —P(O) 2 R ∘ ; —P(O)R ∘ 2 ; —OP(O)R ∘ 2 ; —OP(O)(OR ∘ ) 2 ; SiR ∘ 3 ; —(C 1-4 straight or branched alkylene)O—N(R ∘ ) 2 ; and —(C 1-4 straight or branched alkylene)C(O)O—N(R ∘ ) 2 ,
wherein R ∘ at each occurrence is
independently hydrogen, C 1-8 aliphatic, —CH 2 Ph or —O(CH 2 ) 0-1 Ph; 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;
R d at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R d groups may be taken together to form one or more optionally substituted rings;
each R y is
independently hydrogen; or an optionally substituted group selected the group consisting of:
acyl;
carbamoyl,
arylalkyl;
6- to 10-membered aryl;
C 1-12 aliphatic;
C 1-12 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 R y 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 R 4 is independently a hydroxyl protecting group or R y ;
R 1a , R 1a′ , R 2a , R 2a′ , R 3a , and R 3a′ are
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 (R 2a′ and R 3′ ), (R 2a and R 3a ), (R 1a and R 2a ), and (R 1a′ and R 2′ ) 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 R y groups; and
R 4a is selected from the group consisting of:
wherein:
R c at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R c 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 R c 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: —NR y —, —N(R y )C(O)—, —C(O)NR y —, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR y )—, —N═N—; a polyether; a C 3 to C 8 substituted or unsubstituted carbocycle; and a C 1 to C 8 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.
15. The process of claim 14 , wherein the catalyst replacement component is introduced at a rate that results in less than 10% variation in the rate of the carbonylation reaction over a period of one hour.
16. The process of claim 1 , wherein the epoxide feedstock is continuously reacted with the carbon monoxide in the presence of the carbonylation catalyst in the carbonylation reaction vessel.
17. The process of claim 1 , wherein the epoxide feedstock comprises ethylene oxide.
18. The process of claim 1 , wherein the precursor to the Lewis acid is
19. The process of claim 1 , wherein the precursor to the Lewis acid is
20. The process of claim 1 , wherein the precursor to the Lewis acid is
21. The process of claim 1 , wherein the precursor to the Lewis acid is
22. The process of claim 1 , wherein the precursor to the Lewis acid is
23. The process of claim 1 , wherein the precursor to the Lewis acid is
24. The process of claim 1 , wherein the precursor to the Lewis acid is
25. The process of claim 1 , wherein M is aluminum, chromium, titanium, indium, gallium, zinc, cobalt, or copper.
26. The process of claim 1 , wherein M is aluminum or chromium.
27. The process of claim 1 , wherein the catalyst replacement components have a halide content less than about 200 ppm.
28. 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 R q is independently C 1-12 aliphatic or aryl,
wherein the aryl is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen; —(CH 2 ) 0-4 R ∘ ; —(CH 2 ) 0-4 OR ∘ ; —O—(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 CH(OR ∘ ) 2 ; —(CH 2 ) 0-4 SR ∘ ; —(CH 2 ) 0-4 Ph; —(CH 2 ) 0-4 O(CH 2 ) 0-1 Ph; —CH═CHPh; —NO 2 ; —CN; —N 3 ; —(CH 2 ) 0-4 N(R ∘ ) 2 ; —(CH 2 ) 0-4 N(R ∘ C(O)R ∘ ; —N(R ∘ C(S)R ∘ ; —(CH 2 ) 0-4 N(R ∘ )C(O)NR ∘ 2 ; —N(R ∘ )C(S)NR ∘ 2 ; —(CH 2 ) 0-4 N(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 ∘ ; —(CH 2 ) 0-4 C(O)R ∘ ; —C(S)R ∘ ; —(CH 2 ) 0-4 C(O)OR ∘ ; —(CH 2 ) 0-4 C(O)N(R ∘ ) 2 ; —(CH 2 ) 0-4 C(O)SR ∘ ; —(CH 2 ) 0-4 C(O)OSiR ∘ 3 ; —(CH 2 ) 0-4 OC(O)R ∘ ; —OC(O)(CH 2 ) 0-4 SR ∘ ; —SC(S)SR ∘ ; —(CH 2 ) 0-4 SC(O)R ∘ ; —(CH 2 ) 0-4 C(O)NR ∘ 2 ; —C(S)NR ∘ 2 ; —C(S)SR ∘ , —SC(S)SR ∘ ; —(CH 2 ) 0-4 OC(O)NR ∘ 2 ; —C(O)N(OR ∘ )R ∘ , —C(O)C(O)R ∘ , —C(O)CH 2 C(O)R ∘ ; —C(NOR ∘ )R ∘ ; —(CH 2 ) 0-4 SSR ∘ ; —(CH 2 ) 0-4 S(O) 2 R ∘ ; —(CH 2 ) 0-4 S(O) 2 OR ∘ ; —(CH 2 ) 0-4 OS(O) 2 R ∘ ; —S(O) 2 NR ∘ 2 ; —(CH 2 ) 0-4 S(O)R ∘ ; —N(R ∘ )S(O) 2 NR ∘ 2 ; —N(R ∘ )S(O) 2 R ∘ ; —N(OR ∘ )R ∘ ; —C(NH)NR ∘ 2 ; —P(O) 2 R ∘ ; —P(O)R ∘ 2 ; —OP(O)R ∘ 2 ; —OP(O)(OR ∘ ) 2 ; SiR ∘ 3 ; —(C 1-4 straight or branched alkylene)O—N(R ∘ ) 2 ; and —(C 1-4 straight or branched alkylene)C(O)O—N(R ∘ ) 2 ,
wherein R ∘ at each occurrence is
independently hydrogen, C 1-8 aliphatic, —CH 2 Ph, or —O(CH 2 ) 0-1 Ph; 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;
R d at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R d groups may be taken together to form one or more optionally substituted rings;
each R y is
independently hydrogen; or an optionally substituted group selected the group consisting of:
acyl;
carbamoyl,
arylalkyl;
6- to 10-membered aryl;
C 1-12 aliphatic;
C 1-12 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 R y 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 R 4 is independently a hydroxyl protecting group or R y ;
R 1a , R 1a′ , R 2a , R 2a′ , R 3a , and R 3a′ are
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 (R 2a′ and R 3′ ), (R 2a and R 3a ), (R 1a and R 2a ), and (R 1a′ and R 2′ ) 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 R y groups; and
R 4a is selected from the group consisting of:
wherein:
R c at each occurrence is
independently hydrogen, halogen, —OR 4 , —NR y 2 , —SR y , —CN, —NO 2 , —SO 2 R y , —SOR y , —SO 2 NR y 2 ; —CNO, —NR y SO 2 R y , —NCO, —N 3 , or —SiR y 3 ; or an optionally substituted group selected from the group consisting of:
C 1-20 aliphatic;
C 1-20 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 R c 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 R c 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: —NR y —, —N(R y )C(O)—, —C(O)NR y —, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO 2 —, —C(═S)—, —C(═NR y )—, —N═N—; a polyether; a C 3 to C 8 substituted or unsubstituted carbocycle; and a C 1 to C 8 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.
29. The process of claim 1 , wherein each R q is independently C 1-12 aliphatic.
30. The process of claim 14 , wherein each R q is independently C 1-12 aliphatic.
31. The process of claim 28 , wherein each R q is independently C 1-12 aliphatic.