Methods and compositions for substituted arylcycloheptane analogs
AssigneeUniversity of Florida Research Foundation, Inc.
InventorsAlexander James Grenning, Ehsan Fereyduni
Life of this patent
Estimating the term…
Abstract
In one aspect, the disclosure relates to methods for preparation of intermediates useful for the preparation of aryl-cycloheptene scaffolds. In a further aspect, the disclosed methods pertain to the preparation of compounds comprising an aryl-cycloheptene structure. The disclosed methods utilize abundant starting materials and simple reaction sequences that can be used to modularly and scalably assemble common such cores. In various aspects, the present disclosure pertains to compounds prepared using the disclosed methods. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Claims18
A method of synthesizing a bis-allylated compound, the method comprising:
- reacting a Knoevenagel adduct and chalcone-derived electrophile in the presence of a palladium catalyst and base at a first reaction temperature for a first reaction time;
- wherein the Knoevenagel adduct has a formula represented by a structure:
- wherein each of R1a, R1b, R1c, R1d, R1e and K1f is independently selected from hydrogen, halogens, and C1-C8 alkyl;
- or wherein each of R1a, R1b, R1e and R1f is independently selected from hydrogen and C1-C8 alkyl, and wherein R1c and R1d are optionally combined and form a C3 to C8 cycloalkyl, C3 to C8 cycloalkenyl, or 5-atom or 6-atom heterocycle containing one or more oxygens;
- wherein the chalcone-derived electrophile has a formula represented by a structure:
- wherein Ar1 is a phenyl group optionally substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- and
- wherein Ar2 is a phenyl group optionally substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- and
- wherein at least one of Ar1 and Ar2 is substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- after completion of the first reaction time, adding to the reaction an allylic electrophile and continuing the reaction at second reaction temperature for a second reaction time, wherein the allylic electrophile has a formula represented by a structure:
- wherein X is a halogen;
- and wherein R3 is selected from hydrogen and C1-C8 alkyl;
- thereby synthesizing the bis-allylated compound, wherein the bis-allylated compound has a formula represented by a structure:
A method of synthesizing an aryl-cycloheptene compound, the method comprising:
- reacting a bis-allylated compound in the presence of a Grubbs catalyst, and wherein the bis-allylated compound has a formula represented by a structure:
- wherein each of R1a, R1b, R1c, R1d, R1e, R1f and R3 is independently selected from hydrogen, halogen, and C1-C8 alkyl;
- or wherein each of R1a, R1b, R1e, R1f and R3 is independently selected from hydrogen and C1-C8 alkyl, and wherein R1c and R1d are optionally combined to form a C3 to C8 cycloalkyl, C3 to C8 cycloalkenyl, or 5-atom or 6-atom heterocycle containing one or more oxygens;
- wherein Ar1 is a phenyl group optionally substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- and
- wherein Ar2 is a phenyl group optionally substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- and
- wherein at least one of Ar1 and Ar2 is substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating;
- thereby synthesizing an aryl-cycloheptene compound having a formula represented by a structure:
A compound having a formula represented by a structure:
- wherein each of R1a, R1b, R1c, R1d, R1e, R1f and R3 is independently selected from hydrogen and C1-C8 alkyl;
- or wherein each of R1a, R1b, R1e, R1f and R3 is independently selected from hydrogen, halogen, and C1-C8 alkyl, and wherein R1c and R1d are optionally combined and form a C3 to C8 cycloalkyl, C3 to C8 cycloalkenyl, or 5-atom or 6-atom heterocycle containing one or more oxygens;
- and
- wherein Ar1 is a phenyl group substituted with 1, 2, or 3 groups that are electron-withdrawing or electron-donating.
Dependencies are inferred from the claim text.