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Details for Patent: 6,372,945

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Details for Patent: 6,372,945

Title: Process for the synthesis of vinyl sulfoxides
Abstract:The present invention is directed to a new process for the synthesis of vinyl sulfoxides, in particular diarylvinyl sulfoxides
Inventor(s): Aikins; James A. (Indianapolis, IN), Miller; Randal Scot (Lafayette, IN), Zhang; Tony Y. (Indianapolis, IN)
Assignee: Eli Lilly and Company (Indianapolis, IN)
Filing Date:Jun 07, 1995
Application Number:08/483,130
Claims:1. A process for preparing a compound of the formula ##STR16##

wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino; and

R.sub.3 is a thermally-labile or acid-labile C.sub.4 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group all having a tertiary carbon atom adjacent to the sulfur atom;

comprising the steps of:

(1) oxidizing a benzyl sulfide of the formula: ##STR17##

wherein R.sub.2 and R.sub.3 are as defined above; with an oxidizing agent to produce a benzyl sulfoxide of the formula: ##STR18##

wherein R.sub.2 and R.sub.3 are as defined above;

(2) reacting said benzyl sulfoxide with a first strong base to form a benzylic anion;

(3) condensing said benzylic anion with a benzaldehyde of the formula ##STR19##

wherein R.sub.1 is as defined above;

(4) reacting the condensation product from step 3 with an acid chloride to produce an ester of the formula ##STR20##

wherein:

R.sub.1, R.sub.2, and R.sub.3 are as defined above; and

R.sub.4 is CO(C.sub.1 -C.sub.6 alkyl), CO(aryl), CO(arylalkyl), SO.sub.2 (C.sub.1 -C.sub.6 alkyl), SO.sub.2 (aryl), SO.sub.2 (arylalkyl), CO.sub.2 (C.sub.1 -C.sub.6 alkyl), CO.sub.2 (aryl), CO.sub.2 (arylalkyl), or CON(C.sub.1 -C.sub.6 alkyl).sub.2 ; and

(5) treating said ester with a second strong base.

2. The process of claim 1 wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy; and

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy.

3. The process of claim 2 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.4 -C.sub.10 alkyl or aryl(C.sub.1 -C.sub.10 alkyl) group, all having a tertiary carbon atom adjacent to the sulfur atom.

4. The process of claim 3 wherein the oxidizing agent is peracetic acid.

5. The process of claim 4 wherein the first stong base is an alkyllithium.

6. The process of claim 5 wherein the first strong base is n-butyllithium.

7. The process of claim 5 wherein the acid chloride is a sulfonyl chloride, and R.sub.4 is SO.sub.2 (C.sub.1 -C.sub.6 alkyl), SO.sub.2 (aryl), or SO.sub.2 (arylalkyl).

8. The process of claim 7 wherein the sulfonyl chloride is methanesulfonyl chloride.

9. The process of claim 5 wherein the second strong base is a metal alkoxide.

10. The process of claim 9 wherein the metal alkoxide is potassium t-butoxide.

11. The process of claim 10 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.4 -C.sub.10 alkyl group, all having a tertiary carbon atom adjacent to the sulfur atom.

12. The process of claim 5 wherein R.sub.1 and R.sub.2 are methoxy, and R.sub.3 is t-butyl.

13. A process for preparing a compound of the formula ##STR21##

wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino;

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, arylalkoxy, halo, or amino; and

R.sub.3 is a thermally-labile or acid-labile C.sub.4 -C.sub.10 alkyl, C.sub.4 -C.sub.10 alkenyl, or aryl(C.sub.1 -C.sub.10 alkyl) group all having a tertiary carbon atom adjacent to the sulfur atom;

comprising the steps of:

(1) reacting a benzyl sulfide of the formula: ##STR22##

wherein R.sub.2 and R.sub.3 are as defined above;

with a first strong base to form a benzylic anion;

(2) condensing said benzylic anion with a benzaldehyde of the formula ##STR23##

wherein R.sub.1 is as defined above;

(3) reacting the condensation product from step 2 with an acid chloride to produce an ester of the formula ##STR24##

wherein:

R.sub.1, R.sub.2, and R.sub.3 are as defined above; and

R.sub.4 is CO(C.sub.1 -C.sub.6 alkyl), CO(aryl), CO(arylalkyl), SO.sub.2 (C.sub.1 -C.sub.6 alkyl), SO.sub.2 (aryl), SO.sub.2 (arylalkyl), CO.sub.2 (C.sub.1 -C.sub.6 alkyl), CO.sub.2 (aryl), CO.sub.2 (arylalkyl), or CON(C.sub.1 -C.sub.6 alkyl).sub.2 ;

(4) treating said ester with a second strong base to produce a styryl sulfide of the formula; ##STR25##

wherein R.sub.1, R.sub.2, and R.sub.3 are as defined above; and

(5) oxidizing said styryl sulfide with an oxidizing agent.

14. The process of claim 13 wherein:

R.sub.1 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy; and

R.sub.2 is hydrogen, C.sub.1 -C.sub.4 alkoxy, or arylalkoxy.

15. The process of claim 14 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.4 -C.sub.10 alkyl or aryl (C.sub.1 -C.sub.10 alkyl) group, all having a tertiary carbon atom adjacent to the sulfur atom.

16. The process of claim 14 wherein the oxidizing agent is peracetic acid.

17. The process of claim 16 wherein the first stong base is an alkyllithium.

18. The process of claim 17 wherein the first strong base is n-butyllithium.

19. The process of claim 17 wherein the acid chloride is a sulfonyl chloride, and R.sub.4 is SO.sub.2 (C.sub.1 -C.sub.6 alkyl), SO.sub.2 (aryl), or SO.sub.2 (arylalkyl).

20. The process of claim 19 wherein the sulfonyl chloride is methanesulfonyl chloride.

21. The process of claim 17 wherein the second strong base is a metal alkoxide.

22. The process of claim 21 wherein the metal alkoxide is potassium t-butoxide.

23. The process of claim 22 wherein R.sub.3 is a thermally-labile or acid-labile C.sub.2 -C.sub.10 alkyl group, having a tertiary carbon atom adjacent to the sulfur atom.

24. The process of claim 17 wherein R.sub.1 and R.sub.2 are methoxy, and R.sub.3 is t-butyl.
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