Silylated derivatives of aromatic heterocycles

Patent metadata

Field	Value
Publication number	US-11312733-B2
Application number	US-202017074717-A
Country	US
Kind code	B2
Filing date	Oct 20, 2020
Priority date	Aug 6, 2014
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

The present disclosure describes methods for silylating aromatic derivatives, comprising the use of hydrosilanes and potassium hydroxide.

First claim

What is claimed:

1. A method of preparing a silylated aromatic compound containing an alpha silane group, the silylated compound comprising a moiety of Formula (I), (II), (III), or (IV):

the method comprising:
contacting a precursor substrate containing an exocyclic alkyl group, the substrate comprising a moiety of Formula (IA), (IIA), (IIIA), or (IVA):

respectively, with a hydrosilane of formula (R 1 ) 3-m Si(H) m+1 and potassium hydroxide (KOH), under conditions to form the silylated compound, the method resulting in the formation of the silylated compound containing the moiety of Formula (I), (II), (III), or (IV);
wherein
m is 0, 1, or 2;
R 1 is independently optionally substituted C 1-12 alkyl, optionally substituted C 1-12 heteroalkyl, an optionally substituted aryl, or optionally substituted heteroaryl, and, if substituted, the substituents are independently alkyl, alkenyl, aryl, heteroaryl, hydroxyl, C 1 -C 20 alkoxy, C 5 -C 20 aryloxy, C 2 -C 20 alkoxycarbonyl, C 5 -C 20 aryloxycarbonyl, optionally protected amino, optionally protected carboxyl, carboxylato, cyano, halo, phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato, C 1 -C 20 alkylsulfanyl, C 5 -C 20 arylsulfanyl, C 1 -C 20 alkylsulfonyl, C 5 -C 20 arylsulfonyl, C 1 -C 20 alkylsulfinyl, C 5 -C 20 arylsulfinyl, sulfonamido, amido, imino, nitro, nitroso, mercapto, optionally protected formyl, C 1 -C 20 thioester, cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl, silyloxy, siloxazanyl, boronato, or boryl;
R 2 is H; an optionally substituted linear, branched, cyclic, and/or heteroatom-containing alkyl; or a halo, protected hydroxy, C 1 -C 24 alkoxy, C 2 -C 24 alkenyloxy, C 2 -C 24 alkynyloxy, C 5 -C 24 aryloxy, C 6 -C 24 aralkyloxy, C 6 -C 24 alkaryloxy, optionally protected C 1 -C 24 alkylcarbonyl (—CO— alkyl), optionally protected C 6 -C 24 arylcarbonyl (—CO-aryl)), C 2 -C 24 alkylcarbonyloxy (—O—CO— alkyl), C 6 -C 24 arylcarbonyloxy (—O—CO-aryl)), C 2 -C 24 alkoxycarbonyl ((CO)—O-alkyl), C 6 -C 24 aryloxycarbonyl (—(CO)—O-aryl), halocarbonyl, C 2 -C 24 alkylcarbonato, C 6 -C 24 arylcarbonato, optionally protected carboxy (—COOH), carboxylato (—COO—), carbamoyl (—(CO)—NH 2 ), mono-(C 1 -C 24 alkyl)-substituted carbamoyl (—(CO)NH(C 1 -C 24 alkyl)), di-(C 1 -C 24 alkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24 alkyl) 2 ), mono-(C 1 -C 24 haloalkyl)-substituted carbamoyl (—(CO)—NH(C 1 -C 24 alkyl)), di-(C 1 -C 24 haloalkyl)-substituted carbamoyl (—(CO)—N(C 1 -C 24 alkyl) 2 ), mono-(C 5 -C 24 aryl)-substituted carbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24 aryl)substituted carbamoyl (—(CO)—N(C 5 -C 24 aryl) 2 ), di-N—(C 1 -C 24 alkyl),N—(C 5 -C 24 aryl)-substituted carbamoyl, thiocarbamoyl (—(CS)—NH 2 ), mono-(C 1 -C 24 alkyl)-substituted thiocarbamoyl (—(CO)—NH(C 1 -C 24 alkyl)), di-(C 1 -C 24 alkyl)-substituted thiocarbamoyl (—(CO)—N(C 1 -C 24 alkyl) 2 ), mono-(C 1 -C 24 aryl)substituted thiocarbamoyl (—(CO)—NH-aryl), di-(C 5 -C 24 aryl)-substituted thiocarbamoyl (—(CO)—N(C 5 -C 24 aryl) 2 ), di-N—(C 1 -C 24 alkyl),N—(C 5 -C 24 aryl)-substituted thiocarbamoyl, carbamido (—NH—(CO)—NH 2 ), cyano (—C≡N), cyanato (—O—C═N), thiocyanato (—S—C═N), optionally protected formyl (—(CO)—H), optionally protected thioformyl (—(CS)—H), optionally protected amine, C 1 -C 24 alkylamido (—NH—(CO)-alkyl), C 6 -C 24 arylamido (—NH—(CO)-aryl), imino (—CR═NH where R=hydrogen, C 1 -C 24 alkyl, C 5 -C 24 aryl, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl, C 2 -C 20 alkylimino (—CR═N(alkyl), where R=hydrogen, C 1 -C 24 alkyl, C 5 -C 24 aryl, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl), arylimino (—CR═N(aryl), where R=hydrogen, C 1 -C 20 alkyl, C 5 -C 24 aryl, C 6 -C 24 alkaryl, C 6 -C 24 aralkyl), nitro (—NO 2 ), nitroso (—NO), optionally protected sulfo (—SO 2 OH), sulfonate(SO 2 O—), C 1 -C 24 alkylsulfanyl, C 5 -C 24 arylsulfanyl, C 1 -C 24 alkylsulfinyl (—(SO)-alkyl), C 5 -C 24 arylsulfinyl (—(SO)-aryl), C 1 -C 24 alkylsulfonyl (—SO 2 -alkyl), C 1 -C 24 monoalkylaminosulfonyl-SO 2 —N(H) alkyl), C 1 -C 24 dialkylaminosulfonyl-SO 2 —N(alkyl) 2 , C 5 -C 24 arylsulfonyl (—SO 2 -aryl), boronato (—B(OR) 2 where R is H, alkyl or other hydrocarbyl), phosphono (—P(O)(OH) 2 ), phosphonato (—P(O)(O) 2 ), phosphinato (P(O)(O—)), phospho (—PO 2 ), or phosphine (—PH 2 );
X is NR 3 , O, or S;
R 3 is an amine protecting group, an optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkaryl or optionally substituted alk-heteroaryl;

is a heteroaromatic moiety containing y additional nitrogens in the ring structure, where y=0 or 1 when X is O or S, or y=0, 1, or 2 when X is NR 3 ; and

is an aromatic moiety containing x nitrogen atoms in the ring structure, where x=0, 1, or 2.

2. The method of claim 1 , wherein the silylated compound comprises a moiety of Formula (I) and the precursor comprises a moiety of Formula (IA):

3. The method of claim 1 , wherein the silylated compound comprises a moiety of Formula (II) and the precursor comprises a moiety of Formula (IIA):

4. The method of claim 1 , wherein the silylated compound comprises a moiety of Formula (III) and the precursor comprises a moiety of Formula (IIIA):

5. The method of claim 1 , wherein the silylated compound comprises a moiety of Formula (IV) and the precursor comprises a moiety of Formula (IVA):

6. The method of claim 1 , wherein m=0.

7. The method of claim 1 , wherein m=1.

8. The method of claim 1 , wherein m=2.

9. The method of claim 1 where R 1 is independently optionally substituted cyclic alkyl or branched alkyl or cyclic or branched heteroalkyl.

10. The method of claim 1 , wherein R 1 is independently optionally substituted C 1-12 alkyl, optionally substituted heteroaryl or optionally substituted C 2-12 heterocycloalkyl.

11. The method of claim 1 , wherein R 1 is independently tert-butyl, —C(CH 3 ) 2 (CN), pyridine, or an alkyl substituted heterocycloalkyl.

12. The method of claim 7 where R 1 is independently optionally substituted cyclic alkyl or branched alkyl or cyclic or branched heteroalkyl.

13. The method of claim 7 , wherein R 1 is independently optionally substituted C 1-12 alkyl, optionally substituted heteroaryl or optionally substituted C 2-12 heterocycloalkyl.

14. The method of claim 7 , wherein R 1 is independently tert-butyl, —C(CH 3 ) 2 (CN), pyridine, or an alkyl substituted heterocycloalkyl.

15. The method of claim 1 , wherein x=y=0.

16. The method of claim 1 , wherein X is O or S.

17. The method of claim 1 , wherein X is NR 3 .

18. The method of claim 1 , wherein R 2 is H.

Assignees

• California Inst Of Techn

Inventors

• Toutov Anton
• Betz Kerry
• Fedorov Alexey
• Stoltz Brian M
• Liu Wenbo
• Grubbs Robert H

Classifications

• C07F7/0801 Primary

  General processes · CPC title

• C07F7/0832

  Other preparations · CPC title

• C07D209/12

  Radicals substituted by oxygen atoms · CPC title

• C07F7/0827

  Syntheses with formation of a Si-C bond · CPC title