# US 11,306,097 B2 · Activation of carbonyl beta-carbons for chemical transformations

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- Number: US 11,306,097 B2
- Document ID: US11306097B2
- Status: Granted
- Kind: B2
- Application number: 16/518,839
- Filed: 2019-07-22
- Published: 2019-11-07
- Granted: 2022-04-19
- Earliest claimed: 2013-03-15
- Assignees: Nanyang Technological University
- Applicants: Nanyang Technological University
- Inventors: Yonggui Chi; Zhenqian Fu
- Web page: https://patentgrep.com/patent/US11306097B2

## CPC

- C07D 487/04: Ortho-condensed systems
- C07C 201/12: by reactions not involving the formation of nitro groups
- C07D 207/26: 2-Pyrrolidones
- C07D 207/28: 2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
- C07D 207/50: Nitrogen atoms
- C07D 307/33: in position 2, the oxygen atom being in its keto or unsubstituted enol form
- C07D 307/36: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms
- C07D 333/06: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- C07C 2601/10: the ring being unsaturated
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention relates to a method for synthesizing a compound of Formula (I) as defined herein, comprising: (i) activating a compound of Formula (II) as defined herein, by reacting said compound of Formula (II) with a compound of Formula (III) as defined herein, in the presence of a base, to obtain a compound of Formula (IV) as defined herein; and (ii) reacting the compound of Formula (IV) with an electrophile to obtain the compound of Formula (I). The present invention further relates to the organocatalysts used in the described methods and their respective uses.

## Claims

### Claim 1

A method for synthesizing a compound of Formula (Ia)
wherein
n is 2;
R1 is 2-furyl, propyl, methyl, phenyl, p-tolyl, p-anisyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, or naphthyl,
R2 is hydrogen;
B is
wherein R7 is phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, naphthyl, 2-thiofuryl, o-nitrophenyl, m-nitrophenyl, or p-nitrophenyl,
wherein R8 is phenyl, 2-furyl, p-tolyl, p-chlorophenyl or p-bromophenyl,
wherein Ar is phenyl, p-tolyl, p-chlorophenyl, p-bromophenyl, or 2-thiofuryl; and
NHC⊕ is
comprising:
(i) activating a compound of Formula (IIa)
wherein
LG is —O—C6H4-para-NO2;
by reacting said compound of Formula (IIa) with one of the compounds of Formula (III) in the presence of DBU (1,8-Diazabicyclo[5.4.0]undec-7-en)
to obtain a compound of Formula (IVa)
and
(ii) reacting the compound of Formula (IVa) with an electrophile to obtain the compound of Formula (Ia),
wherein the electrophile is selected from the group consisting of

### Claim 2 (depends on 1)

The method according to claim 1, wherein
NHC⊕ is selected from the group consisting of

### Claim 3 (depends on 2)

The method according to claim 2, wherein NHC⊕ is selected from the group consisting of

### Claim 4 (depends on 1)

The method according to claim 1, wherein NHC⊕ is selected from the group consisting of

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compound of Formula (III) is synthesized from any of the following compounds selected from the group consisting of
wherein X is BF4−.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the compound of Formula (III) is generated in situ from any of the following compounds selected from the group consisting of
wherein X is BF4−

### Claim 7 (depends on 1)

The method according to claim 1, wherein the method is carried out in a solvent selected from the group consisting of tent-Butanol, toluene, THF, CH3CN, CH2Cl2, dioxane, and ethyl acetate.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the reaction temperature of steps (i) and (ii) is 25° C. or 40° C.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the reaction time is about 24 hours.

### Claim 10 (depends on 1)

The method according to claim 1, wherein a molecular sieve is present during the reaction.

### Claim 11 (depends on 10)

The method according to claim 10, wherein the molecular sieve has apertures of a size of approximately 4 Å.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the method comprises further reaction steps selected from catalyst regeneration, michael reaction, aldol reaction, lactonization, and/or decarboxylation.