US 2014/0243404 A1 · UNIQUE HALOGEN-INDUCED CYCLIZATIONS, REAGENTS THEREFOR, AND COMPOUNDS PRODUCED THEREBY

Abstract

This disclosure is related to halonium compounds useful for cyclization of polyenes, alkenoic acids, and alkenyl alkyl ethers, and halogenation of aromatic compounds. The synthesis of such halonium compounds, compounds made using such halonium compounds, and synthesis of natural compounds, including decalins, using the halonium compounds is also disclosed. A representative halonium compound of the disclosure is:

Claims21

Dependent claims

1-122. (canceled)

A compound having the structure:

wherein
Y and X are, independently, a C atom or an O atom,
wherein when X is O, R6 and R13 are absent and when Y is O, R9 and R1, are absent;
Z is a carbon atom;
α, β, and γ are, independently, present or absent, and when present each is a bond;
R1 is OH or a halogen, or is absent if bond γ is present;
R2, R3, R5, R10, R11 and R12 are, independently, H, OH or a C1-4 alkyl;
R4 is H, OH or a CI, alkyl;
R6 is H, OH or a C4 alkyl, or R8 with R7 forms a substituted aryl;
R7 is H, OH, a C1-4 alkyl, or R7 with R8 forms a ═CH2, or R7 with R8 forms a ═O, or R7 is absent when (a) R8 is joined to R9 to form a substituted aryl or unsubstituted aryl, or (b) bond α is present;
R8 is H, OH or a C1-4 alkyl, or R8 with R9 forms a substituted oxane, or R6 with R9 forms a substituted dioxane, or R8 with R9 forms a substituted aryl or an unsubstituted aryl, or R8 with R9 forms the structure:
wherein W is a C atom or an O atom, and when W is an O atom, R18 is absent;
wherein end y′ is bonded to atom Y and end z′ is bonded to atom Z and
wherein when W is a C atom, R15 and R16 are each, independently, H or OH, and R17 and R18 are each, independently, H or OH, or R17 and R18 together form a substituted or unsubstituted aryl,
and wherein when W is an O atom R15 is H or OH, and wherein R16 and R17 are, independently, H or OH, or R16 and R17 together form a substituted aryl or unsubstituted aryl;
R9 is H, —CHO, —CH2OAc, —C(═O)(OEt) or —C(═O)(OMe),
wherein R19 is a substituted aryl or an unsubstituted aryl;
R12 is H, OH or a C1-4 alkyl, or is absent if bond γ is present;
R13 is H or, is absent when (a) R6 is joined to R7 to form a substituted aryl or (b) bond β is present;
R14 is H or, is absent when (a) R9 is joined to R8 to form a substituted aryl or unsubstituted aryl, or (b) Y is an O atom, or (c) bond α is present;
wherein bond α is only present if bond γ is present and R9 is —C(═O)(OEt) or —C(═O)(OMe), and Y and Z are each a C atom;
wherein bond β is only present if bonds α and γ are absent and R9 is —C(═O)(OEt) or —C(═O)(OMe), and Z and X are carbon atoms, and R7 together with R8 is other than ═O;
wherein when Y and X are C atoms, R1 is Br, R2, R3 and R10 are CH3, R4, R8, R6, R11, R12, R13 and R14 are H, R7 and R8 form a ═CH2, and R9 is —CH2—R19 with R19 having the structure:
then R9 and R10 have the following stereochemistry:
wherein when Y and X are C atoms, R1 is Br, R2, R3, R8 and R10 are CH3, R4, R5, R6, R11, R12, R13 and R14 are H, and R7 is OH, then R9 is other than —C2H4C(CH3)(CHCH2OH);
wherein when R9 is —C(═O)(OMe) and bonds α, β, and γ are absent, and R7 and R8 together from ═O, then R1 is other than I, or a pharmaceutically acceptable salt thereof;
or
a composition comprising a compound having the structure:
wherein
Y and X are, independently, a C atom or an O atom,
wherein when X is O, R6 and R13 are absent and when Y is O, R9 and R14 are absent;
Z is a carbon atom;
α, β, and γ are, independently, present or absent, and when present each is a bond;
R1 is OH, CH3 or a halogen, or is absent if bond γ is present;
R2, R2, R5, R10, R11 and R12 are, independently, H, OH or a C1-4 alkyl;
R4 is H, OH or a C1-4 alkyl;
R6 is H, OH or a C1-4 alkyl, or R6 with R7 forms a substituted aryl;
R7 is H, OH, a C1-4 alkyl, or R7 with R8 forms a ═CH, or R7 with R8 forms a ═O, or R7 is absent when (a) Ra is joined to R9 to form a substituted aryl or unsubstituted aryl or (b) bond α is present;
R8 is H, OH or a C1-4 alkyl, or R8 with R9 forms a substituted oxane, or R8 with R9 forms a substituted dioxane, or R6 with R9 forms a substituted aryl or an unsubstituted aryl, or R8 with R9 forms the structure:
wherein W is a C atom or an O atom, and when W is an O atom, R18 is absent;
wherein end y′ is bonded to atom Y and end z′ is bonded to atom Z and
wherein when W is a C atom, R15 and R16 are each, independently, H, or OH, and R17 and R16 are each, independently, H, or OH, or R17 and R18 together form a substituted or unsubstituted aryl,
and wherein when W is an O atom R15 is H, or OH, and wherein R16 and R17 are, independently, H, or OH, or R16 and R17 together form a substituted aryl or unsubstituted aryl;
R9 is H, —CHO, —CH2OAc, —C(═O)(OEt) or —C(═O)(OMe),
wherein R19 is a substituted aryl or an unsubstituted aryl;
R12 is H, OH or a C1-4 alkyl, or is absent if bond γ is present;
R13 is H or, is absent when (a) R6 is joined to R7 to form a substituted aryl or (b) bond β is present;
R14 is H or, is absent when (a) R9 is joined to R8 to form a substituted aryl or unsubstituted aryl, or (b) Y is an O atom, or (c) bond α is present;
wherein bond α is only present if bond γ is present and R9 is —C(═O)(OEt) or —C(═O)(OMe), and Y and Z are carbon atoms;
wherein bond β is only present if bonds α and γ are absent and R9 is —C(═O)(OEt) or —C(═O)(OMe), and Z and X are carbon atoms, and R7 together with R8 is other than ═O;
wherein when Y and X are C atoms, R1 is Br, R2, R3, R8 and R10 are CH3, R4, R5, R6, R11, R12, R13 and R14 are H, R7 is OH then R9 is other than —C2H4C(CH3)(CHCH2OH), or a pharmaceutically acceptable salt thereof,
wherein the composition is free of plant extract.

49 more elements

A compound having the structure:

wherein
R44, R45, R46, R47, R48, and R49 are independently H, CN, acetate, OH, OR50, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C2-6 alkenyl, a ketone, an ester, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocyclyl,
wherein each occurrence of R50 is independently H, methyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, phosphate, sulfate, sulfonic ester, or ester,
or a pharmaceutically acceptable salt thereof;
or
a composition comprising a compound having the structure:
wherein
R44, R45, R46, R47, R48, and R49 are independently H, CN, acetate, OH, OR50, a substituted or unsubstituted C1-6 alkyl, a substituted or unsubstituted C2-6 alkenyl, a ketone, an ester, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkenyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted heterocyclyl,
wherein each occurrence of R50 is independently H, methyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, phosphate, sulfate, sulfonic ester, or ester,
or a pharmaceutically acceptable salt thereof,
wherein the composition is free of plant extract.

8 more elements

A compound having the structure having the structure:

wherein
R62, R63, R64, R65, R66, and R67 are independently H, methyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, phosphate, sulfate, sulfonic ester, or ester;
and
R68 and R69 are independently H, Cl, Br or I,
or a pharmaceutically acceptable salt thereof;
or
a composition comprising a compound having the structure:
wherein
R62, R63, R64, R65, R66, and R67 are independently H, methyl, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, phosphate, sulfate, sulfonic ester, or ester;
and
R68 and R69 are independently H, Cl, Br or I,
or a pharmaceutically acceptable salt thereof,
wherein the composition is free of plant extract.

10 more elements

Dependencies are inferred from the claim text.

Unique halogen-induced cyclizations, reagents therefor, and compounds produced thereby

Life of this patent

Unique halogen-induced cyclizations, reagents therefor, and compounds produced thereby

Life of this patent

Abstract

Claims21