Synthesis of straight-chain lepidopteran pheromones through one- or two-carbon homologation of fatty alkenes
Methods for the preparation of alkenes including insect pheromones are described. The methods include homologation reactions employing reagents such as 1,3-diesters, epoxides, cyanoacetates, and cyanide salts for elongation of starting materials and intermediates by one or two carbon atoms. The alkenes include insect pheromones useful in a number of agricultural applications.
1. A method for the preparation of a C 6 -C 18 alkene product, the method comprising contacting a C 4 -C 17 alkene reactant with a homologation reagent under conditions sufficient to form the C 6 -C 18 alkene product, wherein the C 6 -C 18 alkene product comprises a 7-unsaturated alkene, an 8-unsaturated alkene, a 9-unsaturated alkene, or an 11-unsaturated alkene, wherein the C 4 -C 17 alkene reactant is an alkenyl Grignard reagent, an alkenyl sulfonate, or an alkenyl halide, and wherein the C 6 -C 18 alkene product is not a benzyl ether.
2. The method of claim 1 , wherein the homologation reagent is an epoxide, a 1,3-diester, a cyanoacetate, a cyanide salt, an orthoester, a haloacetal, a haloalkyl ether, formaldehyde, or a formaldehyde precursor.
3. The method of claim 1 , comprising contacting a C 6 -C 17 alkene reactant with the homologation reagent under conditions sufficient to form a C 8 -C 18 alkene product.
4. The method of claim 1 , wherein the C 4 -C 17 alkene reactant is an alkenyl Grignard reagent, the homologation reagent is an epoxide, and the C 6 -C 18 alkene product is an alkenol.
5. The method of claim 4 , further comprising acylating the alkenol under conditions sufficient to form an alkenol ester, and optionally contacting the alkenol ester with a C 2 -C 10 alkene in the presence of a metathesis catalyst under conditions sufficient form a metathesis product.
6. The method of claim 1 , wherein the C 4 -C 17 alkene reactant is an alkenyl halide or an alkenyl sulfonate, the homologation reagent is a 1,3-diester, and the C 6 -C 18 alkene product is a 2-(alkenyl) malonate.
7. The method of claim 6 , further comprising converting the 2-(alkenyl) malonate to an alkenoic acid.
8. The method of claim 7 , further comprising esterifying the alkenoic acid to form an alkyl alkenoate.
9. The method of claim 8 , further comprising contacting the alkyl alkenoate with a C 2 -C 10 alkene in the presence of a metathesis catalyst under conditions sufficient to form an alkyl alkenoate metathesis product.
10. The method of claim 9 , further comprising contacting the alkyl alkenoate metathesis product with a reducing agent under conditions sufficient to form an alkenol, optionally contacting the alkenol with an acylating agent under conditions sufficient to form an alkenol ester, and optionally contacting the alkyl alkenoate metathesis product with a reducing agent under conditions sufficient to form an alkenal.
11. The method of claim 7 , further comprising reducing the alkenoic acid to form an alkenol, optionally acylating the alkenol under conditions sufficient to form an alkenol ester, and optionally contacting the alkenol ester with a C 2 -C 10 alkene in the presence of a metathesis catalyst under conditions sufficient to form a metathesis product.
12. The method of claim 1 , wherein:
the C 4 -C 17 alkene reactant is an alkenyl halide or an alkenyl sulfonate, the homologation reagent is a cyanoacetate, and the C 6 -C 18 alkene product is an alkyl (2-cyano) alkenoate, and the method further comprises decarboxylating the alkyl (2-cyano) alkenoate to form an alkenyl nitrile; or
the C 4 -C 17 alkene reactant is an alkenyl sulfonate or an alkenyl halide, the homologation reagent is a cyanide salt, and the C 6 -C 18 alkene product is an alkenyl nitrile.
13. The method of claim 12 , further comprising reducing the alkenyl nitrile to form an alkenal.
14. The method of claim 13 , further comprising reducing the alkenal to form an alkenol, optionally acylating the alkenol under conditions sufficient to form an alkenol ester, and optionally contacting the alkenol ester with a C 2 -C 10 alkene in the presence of a metathesis catalyst under conditions sufficient to form a metathesis product.
15. The method of claim 1 , wherein the C 4 -C 17 alkene reactant is an alkenyl Grignard reagent, the homologation reagent is a haloacetal or an orthoester, and the C 6 -C 18 alkene product is an alkenal.
16. The method of claim 15 , further comprising reducing the alkenal under conditions sufficient to form an alkenol, and optionally acylating the alkenol under conditions sufficient to form an alkenol ester.
17. The method of claim 1 , wherein:
the C 4 -C 17 alkene reactant is an alkenyl Grignard reagent, the homologation reagent is a haloalkyl ether, and the C 6 -C 18 alkene product is an alkenyl ether, and the method further comprises converting the alkenyl ether to an alkenol; or
the C 4 -C 17 alkene reactant is an alkenyl Grignard reagent, the homologation reagent is formaldehyde or a formaldehyde precursor, and the C 6 -C 18 alkene product is an alkenol.
18. The method of claim 17 , further comprising acylating the alkenol under conditions sufficient to form an alkenol ester.