Top > Search of International Patents > Process of making alpha-aminooxyketone/alpha-aminooxyaldehyde and alpha-hydroxyketone/alpha-hydroxyaldehyde compounds and a process making reaction products from cyclic alpha, beta-unsaturated ketone substrates and nitroso substrates

Process of making alpha-aminooxyketone/alpha-aminooxyaldehyde and alpha-hydroxyketone/alpha-hydroxyaldehyde compounds and a process making reaction products from cyclic alpha, beta-unsaturated ketone substrates and nitroso substrates

Foreign code F110005360
File No. B12-03US
Posted date Sep 5, 2011
Country United States of America
Application number 57883609
Gazette No. 20100099915
Gazette No. 8252941
Date of filing Oct 14, 2009
Gazette Date Apr 22, 2010
Gazette Date Aug 28, 2012
International application number US2005005426
International publication number WO2005090294
Date of international filing Feb 18, 2005
Date of international publication Sep 29, 2005
Priority data
  • P2004-044540 (Feb 20, 2004) JP
  • 2004US-60564048 (Apr 20, 2004) US
  • 2005WO-US05426 (Feb 18, 2005) WO
  • 2006US-11506590 (Oct 25, 2006) US
Title Process of making alpha-aminooxyketone/alpha-aminooxyaldehyde and alpha-hydroxyketone/alpha-hydroxyaldehyde compounds and a process making reaction products from cyclic alpha, beta-unsaturated ketone substrates and nitroso substrates
Abstract (US8252941)
The present invention is directed to a process of making α-aminooxyketone and α-hydroxyketone compounds.
The synthetic pathway generally involves reacting an aldehyde or ketone substrate and a nitroso substrate in the presence of a catalyst of the formula (IV): wherein Xa―Xc represent independently nitrogen, carbon, oxygen or sulfur and Z represents a 4 to 10-membered ring with or without a substituent and optionally a further step to convert the α-aminooxyketone compound formed to the α-hydroxyketone compound.
The present invention results in α-aminooxyketone and α-hydroxyketone compounds with high enantioselectivity and high purity.
The present invention is also directed to a catalytic asymmetric O-nitroso Aldol/Michael reaction.
The substrates of this reaction are generally cyclic α,β-unsaturated ketone substrate and a nitroso substrate.
This methodology generally involves reacting the cyclic α,β-unsaturated ketone substrate and the nitroso substrate in the presence of a proline-based catalyst, to provide a heterocyclic product.
Scope of claims [claim1]
1. A process of making an enantioenriched alpha -aminooxyketone comprising reacting a ketone of formula (II):
with a nitroso compound of formula (IIIa) or (IIIb):
in the presence of a solvent and a catalyst of formula (IVa):
wherein:
R1 and R2 independently represent either hydrogen; a substituted or unsubstituted alkyl group; a substituted or unsubstituted alkoxy group; a substituted or unsubstituted alkoxycarbonyl group; a substituted or unsubstituted aryl group; or
R1 and R2 together form a cycloalkyl ring;
R3 is each independently selected from the group consisting of:
hydrogen, halogen, -- OR5, -- OC(O)R5, -- CN, -- C(O)R5, -- CO2R5, -- C(O)NR5R5', -- NO2, -- NR5R5', -- NRC(O)R5, -- NR5CO2R5', -- NR5S(O)2R5', -- SR5, -- S(O)R5, -- S(O)2R5, -- S(O)2NR5R5', C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl; wherein each R5 and R5' may be independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl;
n is an integer from 0-5;
R4 is substituted or unsubstituted alkyl;
the configuration of the stereogenic carbon alpha to the nitrogen on the pyrolidine ring is the (L) or optionally (D) configuration.
[claim2]
2. The process of claim 1 wherein: R1 and R2 independently represent either hydrogen; a substituted or unsubstituted C1-C8 alkyl group; a substituted or unsubstituted C1-C8 alkoxy group; a substituted or unsubstituted C1-C8 alkoxycarbonyl group; a substituted or unsubstituted aryl group, wherein the groups when substituted are substituted by the group consisting of hydrogen, halogen, -- OR4, -- OC(O)R4, -- CN, -- C(O)R4, -- CO2R4, -- C(O)NR4R5, -- NO2, -- NR4R5, -- NRC(O)R4, -- NR4CO2R5, -- NR4S(O)2R5, -- SR4, -- S(O)R4, -- S(O)2R4, -- S(O)2NR4R5, C1-8 alkyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl; or
R1 and R2 together form a C3-C8 cycloalkyl ring;
R3 is each independently selected from the group consisting of: hydrogen, halogen, -- OR5, -- OC(O)R5, -- CN, -- C(O)R5, -- CO2R5, -- C(O)NR5R5', -- NO2, -- NR5R5', -- NRC(O)R5, -- NR5CO2R5', -- NR5S(O)2R5', -- SR5, -- S(O)R5, -- S(O)2R5, -- S(O)2NR5R5', C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl; wherein each R5 and R5' may be independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl;
R4 is a substituted or unsubstituted C1-C8 alkyl, wherein when substituted are substituted by the group consisting of halogen, -- OR5, -- OC(O)R5, -- CN, -- C(O)R5, -- CO2R5, -- C(O)NR5R5', -- NO2, -- NR5R5', -- NRC(O)R5, -- NR5CO2R5', -- NR5S(O)2R5', -- SR5, -- S(O)R5, -- S(O)2R5, -- S(O)2NR5R5', C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl; wherein each R5 and R5' may be independently selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocyclyl;
n is an interger from 0-3; and
the configuration of the stereogenic carbone alpha to the nitrogen on the pyrolidine ring is the (L) or optionally (D) configuration.
[claim3]
3. The process of claim 1 wherein the enantioselectivity is greater than 99% enantiomeric excess (ee).
[claim4]
4. The process of claim 1 wherein the catalyst has the following structure:
  • Inventor, and Inventor/Applicant
  • MOMIYAMA NORIE
  • TORII HIROMI
  • SAITO SUSUMU
  • YAMAMOTO HISASHI
  • YAMAMOTO YUHEI
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
IPC(International Patent Classification)
Reference ( R and D project ) SORST Selected in Fiscal 2000
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