Diaryl phosphine compounds
A method for making diazo-compounds, diazonium salts thereof and other protected forms of these compounds. Diazo-compounds are prepared by reaction of a tertiary phosphine reagent carrying a reactive carbonyl group with an azide. The reaction can also generate an acyl triazene which can be converted thermally or by addition of base to form the diazo-compound or the acyl triazene can be isolated. The method is particularly useful for conversion of azides carrying one or more electron withdrawing groups to diazo-compounds. The method can be carried out in aqueous medium under mild conditions and is particularly useful for conversion of azido sugars to diazo-compounds and diazonium salts thereof under physiological conditions. Tertiary phosphine reagents, particularly those that are water-soluble, and precursors for preparation of the reagents are provided.
1. The tertiary phosphine of formula:
wherein:
n is an integer ranging from 1-5 inclusive;
—O—R 5 is:
(1) an —ON(R 7 ) 2 group, an —O—NR 7 —CO—R 7 group or an —O—N(COR 7 )—COR 7 group, where each R 7 is an optionally substituted alkyl or aryl, or where the two R 7 groups together form an optionally substituted 5-8 member heterocyclic ring having one or more heteroatoms or —CO— groups or both in the ring;
(2) a phenyloxy group substituted with one or more halogens, hydroxy, nitro, alkyl, alkenyl, alkynyl, aryl, halogenated alkyl, hydroxy-substituted alkyl, amino-substituted alkyl, cyano, isocyano, thiocyano isothiocyano —SO 2 —SO 3 R, —N(R) 2 , —COR, —COOR, —CON(R) 2 , —NR—CO—NR—, —CO—SR, —OR, or —SR, where each R, independently, is hydrogen, alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, halogenated aryl, heteroaryl, or heterocyclic groups, or two R together form a 5-8 member optionally substituted heterocyclic ring containing one or more heteroatoms, optionally one or more —CO— groups or both;
(3) —O—R 5 where R 5 is an optionally substituted heterocylic or heteroaromatic group; or
(4) —O—SO 2 —O—R S where R S is halogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted phenyl, halogenated alkyl, halogenated aryl, halogenated phenyl, fluorinated alkyl, fluorinated aryl, fluorinated phenyl, unsubstituted alkyl, unsubstituted phenyl, methyl, ethyl, —CF 3 , or —C 4 F 9 ; and
Y 1 and Y 2 are alkoxyalkyl groups.
2. The phosphine of claim 1 wherein R 5 is a nitro- or halogen-substituted phenyl group.
3. The phosphine of claim 1 wherein R 5 is a pentafluorophenyl, a 2,4,6-triclorophenyl or a 4-nitrophenyl group.
4. The phosphine of claim 1 wherein the alkoxyalkyl groups have from 2 to 10 carbon atoms.
5. The phosphine of claim 1 wherein the alkoxyalkyl groups are those which have formula: —[(CH 2 )a-O-]b-CH 3 , where a is 1-10 and b is 1-6.
6. The phosphine of claim 5 wherein —R 5 is a 4-nitrophenyl group or an N-hydroxy succinimide.
7. The phosphine of claim 5 wherein —R 5 is a 4-nitrophenyl group.
8. The phosphine of claim 1 which is linked to a solid.
9. The phosphine of claim 1 wherein —O—R 5 is a phenyloxy group substituted with one or more halogens, hydroxy, nitro, alkyl, alkenyl, alkynyl, aryl, halogenated alkyl, hydroxy-substituted alkyl, amino-substituted alkyl, cyano, isocyano, thiocyano, isothiocyano, —SO 2 , —SO 3 R, —N(R) 2 , —COR, —COOR, —CON(R) 2 , —NR—CO—NR—, —CO—SR, —OR, or —SR, where each R, independently, is hydrogen, alkyl, halogenated alkyl, alkenyl, alkynyl, aryl, halogenated aryl, heteroaryl, or heterocyclic groups, or two R together form a 5-8 member optionally substituted heterocyclic ring containing one or more heteroatoms, optionally one or more —CO— groups or both.
10. The phosphine of claim 1 wherein —O—R 5 is a phenyloxy group substituted with a nitro group.
11. The phosphine of claim 1 wherein —R 5 is a 4-nitrophenyl group or an N-hydroxy succinimide.
12. The phosphine of claim 1 wherein —R 5 is a 4-nitrophenyl group.
13. The phosphine of claim 1 wherein the alkoxyalkyl groups have from 3 to 6 carbon atoms.