Alkenes as alkyne equivalents in radical cascades terminated by fragmentations

Patent metadata

Field	Value
Publication number	US-9708351-B2
Application number	US-201615143669-A
Country	US
Kind code	B2
Filing date	May 2, 2016
Priority date	May 28, 2015
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

Disclosed are methods for rerouting radical cascade cyclizations by using alkenes as alkyne equivalents. The reaction sequence is initiated by a novel 1,2 stannyl shift which achieves chemo- and regioselectivity in the process. The radical “hopping” leads to the formation of the radical center necessary for the sequence of selective cyclizations and fragmentations to follow. In the last step of the cascade, the elimination of a rationally designed radical leaving group via β-C—C bond scission aromatizes the product without the need for external oxidant. The Bu 3 Sn moiety, which is installed during the reaction sequence, allows further functionalization of the product via facile reactions with electrophiles as well as Stille and Suzuki cross-coupling reactions. This selective radical transformation opens a new approach for the controlled transformation of enynes into extended polycyclic structures of tunable dimensions.

First claim

What is claimed is:

1. A method of synthesizing a Sn-functionalized aromatic compound comprising a fused aromatic ring system, the method comprising contacting a stannane compound and a reactant compound having the following structure (I)-a:

wherein:
each R 1 R 2 , R 3 , and R 4 independently comprises hydrogen, alkenyl, alkynyl, aryl, or any two adjacent R 1 R 2 , R 3 , and R 4 together form a fused aromatic ring system;
X is selected from the group consisting of hydroxyl, alkoxy, amino, and phenyl; and
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted;
and wherein the Sn-functionalized aromatic compound comprising a fused aromatic ring system has the following structure (IV)-b:

wherein:
each R 1 R 2 , R 3 , and R 4 independently comprises hydrogen, alkenyl, alkynyl, aryl, or any two adjacent R 1 R 2 , R 3 , and R 4 together form a fused aromatic ring system;
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted; and
each R 5 independently comprises alkyl, aryl, or heteroaryl.

2. The method of claim 1 wherein X is selected from the group consisting of hydroxyl and amine.

3. The method of claim 1 wherein Ar is substituted with an alkenyl, an alkynyl, or both an alkenyl and an alkynyl.

4. The method of claim 1 wherein the reactant compound has the following structure (I)-a:

wherein:
each R 1 R 2 , R 3 , and R 4 independently comprises hydrogen, alkenyl, alkynyl, aryl, or any two adjacent R 1 R 2 , R 3 , and R 4 together form a fused aromatic ring system;
X is selected from the group consisting of hydroxyl and amine; and
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted.

5. The method of claim 1 wherein the reactant compound has any of the following structures (III)-a, (III)-b, and (III)-c:

wherein:
X is selected from the group consisting of hydroxyl, alkoxy, amino, and phenyl; and
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted.

6. The method of claim 1 further comprising contacting the Sn-functionalized aromatic compound comprising a fused aromatic ring system with an acid to thereby prepare a substituted naphthalene having the structure (V)-b:

wherein:
each R 1 R 2 , R 3 , and R 4 independently comprises hydrogen, alkenyl, alkynyl, aryl, or any two adjacent R 1 R 2 , R 3 , and R 4 together form a fused aromatic ring system; and
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted.

7. The method of claim 1 further comprising contacting the Sn-functionalized aromatic compound comprising a fused aromatic ring system with an organic precursor compound to prepare a substituted naphthalene having the structure (VI)-b:

wherein:
each R 1 R 2 , R 3 , and R 4 independently comprises hydrogen, alkenyl, alkynyl, aryl, or any two adjacent R 1 R 2 , R 3 , and R 4 together form a fused aromatic ring system;
Ar comprises aryl or heteroaryl, which may be unsubstituted or substituted; and
R 6 is selected from the group consisting of alkyl, aryl, heteroaryl, amino, alkoxy, and halo.

Assignees

• Univ Florida State Res Found

Inventors

• Alabugin Igor V
• Mondal Sayantan
• Mohamed Rana K

Classifications

• C07D239/26

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07C43/166

  having unsaturation outside the aromatic rings · CPC title

• C07C253/30

  by reactions not involving the formation of cyano groups · CPC title

• C07C17/093

  by replacement by halogens · CPC title

• C07C45/00

  Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds · CPC title