IP Library › Granted Patent US 9,676,743

Granted Patent B2

US 9,676,743 · App. 14/017,803 · Granted Jun 13, 2017

Substituted 3-hydroxy-δ-lactones from epoxides

Inventors: Geoffrey W. Coates (Lansing, NY); John W. Kramer (Ithaca, NY)

Assignee: Cornell University

C07D309/30 C07D311/96 C07D405/06

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Quick Facts

Patent No.: US 9,676,743
App. No.: 14/017,803
Granted: Jun 13, 2017
Kind: B2

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Abstract

Catalysts and methods for the carbonylation of epoxides to substituted 3-hydroxy-δ-lactones and β-lactones are disclosed.

Claims (205)

1. A method comprising steps of:

reacting an epoxide of formula S-Ia′:

wherein:

P′ is hydrogen;

Q′ is selected from the group consisting of: hydrogen; halogen; (a) C 1 to C 20 alkyl; (b) C 2 to C 20 alkenyl; (c) C 2 to C 20 alkynyl; (d) up to a C 16 carbocycle; (e) up to a C 16 heterocycle; and (f) —C(R 13 ) z H (3-z) ; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 10 at each occurrence can be independently selected from the group consisting of: hydrogen; —C(R 13 ) z H (3-z) ; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; up to a C 12 carbocycle; up to a C 12 heterocycle; —S(O) 2 R 13 ; —Si(R 15 ) 3 ; and a hydroxyl protecting group;

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 11 and R 12 ; when both present, can optionally be taken together with the atom to which they are attached to form an optionally substituted 3- to 10-membered ring, optionally containing one or more additional heteroatoms;

R 13 at each occurrence can be independently selected from the group consisting of: hydrogen; halogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; up to a C 12 carbocycle; or up to a C 12 heterocycle;

R 14 at each occurrence can be independently selected from the group consisting of halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 C(O)R 13 ; —NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

Z is a divalent linker and can be selected from the group consisting of: —(CH═CH) a —; —(CH≡CH) a —; —C(O)—; —C(═NOR 11 )—; —C(═NNR 11 R 12 )—; —O—; —N(R 11 )—; —N(C(O)R 13 )—; —S(O) x —; a polyether; and a polyamine;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein:

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 14 at each occurrence can be independently selected from the group consisting of halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 C(O)R 13 ; —NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 14 at each occurrence can be independently selected from the group consisting of halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; NR 11 C(O)R 13 ; —NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; S(O) x R 13 ; —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3; or

wherein the

moiety of S-Ia′ is selected from:

wherein R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 14 at each occurrence can be independently selected from the group consisting of halogen; OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 C(O)R 13 ; —NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 , —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3;

with carbon monoxide (CO) in the presence of a catalytically effective amount of a catalyst of the formula:

[Lewis acid] u+ {[QT(CO) v ] s− } t II

wherein:

Q is any ligand or set of ligands and need not be present;

T is a metal selected from group 7, 8, or 9 of the periodic table;

s is an integer from 1 to 4 inclusive;

t is a number such that t multiplied by s equals u;

u is an integer from 1 to 6 inclusive;

v is an integer from 1 to 9 inclusive; and

the Lewis acid is H+ or is of formula IIIa or IIIb,

wherein the Lewis acid of formula IIIa is:

wherein:

M is a transition metal or group 13 or 14 metal;

L is a ligand and need not be present;

R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring; and

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 11 and R 12 , when both present, can optionally be taken together with the atom to which they are attached to form an optionally substituted 3- to 10-membered ring, optionally containing one or more additional heteroatoms;

R 14 at each occurrence can be independently selected from the group consisting of halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; NR 11 C(O)R 13 ; ——NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; S(O) x R 13 ; —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2;

z can be 1, 2, or 3; and

the Lewis acid of formula IIIb is:

wherein:

M is a transition metal or group 13 or 14 metal;

L is a ligand and need not be present;

R 1 and R 1′ are independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—R 14 ;

R 2 , R 2′ , R 3 , and R 3′ are independently selected from the group consisting of: (i) C 1 -C 12 alkyl; (ii) C 2 -C 12 alkenyl; (iii) C 2 -C 12 alkynyl; (iv) up to a C 12 carbocycle; (v) up to a C 12 heterocycle; (vi) —(CH 2 ) k R 14 ; (vii) R 20 ; and (viii) —C(R 13 ) z H (3-z) ,

wherein each of (i) through (v) may optionally be further substituted with one or more R 20 groups; and where R 2 and R 3 , and R 2′ and R 3′ 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 20 groups;

R 4 is selected from the group consisting of:

wherein X′ is a divalent linker selected from the group consisting of: —N(R 11 )—; —O—; —S(O) x —; —(CH 2 ) k —; —C(O)—; —C(═NOR 10 )—; —C(R f ) 2 —; a polyether; a C 3 to C 8 substituted or unsubstituted carbocycle; and a C 1 to C 8 substituted or unsubstituted heterocycle;

R e at each occurrence is independently selected from the group consisting of: hydrogen; C 1 -C 12 alkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; aryl; heteroaryl; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(R 13 ) z H (3-z) ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 R 12 ; NR 11 C(O)R 10 ; —NR 11 C(O)OR 13 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; —S(O) x R 13 ; —SO 2 NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —(CH 2 ) k R 14 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 , where two or more R e groups may optionally be taken together to form an optionally substituted ring;

R f at each occurrence is independently selected from the group consisting of: (a) C 1 -C 12 alkyl; (b) C 2 -C 12 alkenyl, (c) C 2 -C 12 alkynyl; (e) up to a C 12 carbocycle, (f) up to a C 12 heterocycle; (g) R 20 ; and (h) —C(R 13 ) z H (3-z) ; or wherein:

two or more R f groups may be taken together with the carbon atoms to which they are attached to form one or more rings; or

wherein when two R f groups are attached to the same carbon atom, they may be taken together to form a moiety selected from the group consisting of: a 3- to 8-membered spirocyclic ring; a carbonyl (C═O), an oxime (C═NOR 10 ); a hydrazone (C═NNR 11 R 12 ); an imine (C═NR 11 ); and an alkenyl group (C═CR 11 R 12 );

R 20 at each occurrence is independently selected from the group consisting of: hydrogen; halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —C(R 13 ) z H (3-z) ; —NR 11 R 12 ; —NR 11 C(O)R 10 ; —NR 11 C(O)OR 10 ; —NCO; —NR 12 SO 2 R 13 ; —S(O) x R 13 ; —S(O) 2 NR 11 R 12 ; —NO 2 ; —N 3 ; —(CH 2 ) k R 14 ; —(CH 2 ) k —Z—R 16 ; and —(CH 2 ) k —Z—(CH 2 ) m —R 14 ;

R 11 and R 12 at each occurrence can be independently selected from the group consisting of: hydrogen; C 1 to C 12 alkyl; C 2 to C 12 alkenyl; C 2 to C 12 alkynyl; and —C(R 13 ) z H (3-z) ;

R 14 at each occurrence can be independently selected from the group consisting of halogen; —OR 10 ; —OC(O)R 13 ; —OC(O)OR 13 ; —OC(O)NR 11 R 12 ; —CN; —CNO; —C(R 13 ) z H (3-z) ; —C(O)R 13 ; —C(O)OR 13 ; —C(O)NR 11 R 12 ; —NR 11 C(O)R 13 ; —NR 11 C(O)OR 10 ; —NR 11 SO 2 R 13 ; —NCO; —N 3 ; —NO 2 ; S(O) x R 13 ; —SO 2 NR 11 R 12 ; up to a C 12 heterocycle; and up to a C 12 carbocycle;

R 15 at each occurrence can be independently selected from the group consisting of: C 1 to C 6 alkyl; C 2 to C 6 alkenyl; C 2 to C 6 alkynyl; and up to C 12 substituted or unsubstituted carbocycle;

a can be 1, 2, 3, or 4;

k can be an integer from 1 to 8 inclusive;

m can be an integer from 1 to 8 inclusive;

x can be 0, 1, or 2; and

z can be 1, 2, or 3;

to produce a compound of the formula S-I′:

2. The method of claim 1 , wherein the statin molecule is selected from the group consisting of: cerivastatin, fluvastatin, pitavastatin, and rosuvastatin.

3. The method of claim 2 , wherein the statin molecule is rosuvastatin.

4. The method of claim 2 , wherein the statin molecule is cerivastatin.

5. The method of claim 2 , wherein the statin molecule is fluvastatin.

6. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

7. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

8. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

9. The method of claim 2 , wherein the statin molecule is pitavastatin.

10. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

11. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

12. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

13. The method of claim 1 , wherein the

moiety is selected from the group consisting of:

14. The method of claim 1 , wherein T is cobalt.

15. The method of claim 1 , wherein Q is absent.

16. The method of claim 1 , wherein v is 4.

17. The method of claim 1 , wherein the Lewis acid is H + .

18. The method of claim 1 , wherein the carbonylation catalyst is HCo(CO) 4 .

19. The method of claim 1 , wherein M is Al.

20. The method of claim 19 , wherein the Lewis acid is of formula IIIa(ii):

wherein -Ph, represents an optionally substituted phenyl group.

21. The method of claim 19 , wherein the carbonylation catalyst is of formula IIa(i):

22. The method of claim 1 , wherein the Lewis acid is of formula IIIb(i):

wherein M is Al and L is a ligand and need not be present.

23. The method of claim 22 , wherein the carbonylation catalyst is of formula IIb(ii):

24. The method of claim 1 , wherein the carbonylation proceeds with retention of stereochemistry.

25. The method of claim 1 , wherein the

moiety of S-Ia′ is selected from:

Assignments (4)

CONFIRMATORY LICENSE Recorded Jul 25, 2018

From: CORNELL UNIVERSITY

To: NATIONAL SCIENCE FOUNDATION

Reel/Frame 046623/0581 →

CONFIRMATORY LICENSE Recorded Dec 30, 2014

From: CORNELL UNIVERSITY

To: ENERGY, UNITED STATES DEPARTMENT OF

Reel/Frame 034752/0759 →

CONFIRMATORY LICENSE Recorded Jul 10, 2014

From: CORNELL UNIVERSITY RESEARCH FOUNDATION

To: NATIONAL SCIENCE FOUNDATION

Reel/Frame 033290/0121 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 10, 2013

From: COATES, GEOFFREY W.; KRAMER, JOHN W.

To: CORNELL UNIVERSITY

Reel/Frame 031176/0352 →

Continuity (3)

Continuation 12592280 · Nov 20, 2009

Provisional Application 61116609 · Nov 20, 2008

Related Publication 20140107339A1 · Apr 17, 2014