Stereoselective synthesis of dibenzoxapine containing tetrasubstituted exocyclic alkenes via cascade methylboronic acid coupling reactions

Tetrahedron Letters

Volumn 49, Issue 12, 2008, Pages 1915-1918

  Yu, Hannah ^a   Richey, Rachel N ^a   Mendiola, Javier ^b   Adeva, Marta ^b   Somoza, Carmen ^b   May, Scott A ^a   Carson, Matthew W ^a   Coghlan, Michael J ^a  

^a ELI LILLY AND COMPANY   (United States)

^b ELI LILLY AND COMPANY   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENE; ALKYNE; BORONIC ACID DERIVATIVE; DIBENZOXAZEPINE DERIVATIVE; METHYLBORONIC ACID; UNCLASSIFIED DRUG; VINYL DERIVATIVE; VINYLPALLADIUM;

ARTICLE; CHEMICAL ANALYSIS; STEREOCHEMISTRY; SUBSTITUTION REACTION; SYNTHESIS;

EID: 39149083789     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2008.01.099     Document Type: Article

References (25)

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21. The undesired diastereomers were not detectable by NMR in crude reaction mixtures.
22. 3, 344.1287; found, 344.1294.
23. The E/Z isomerization could occur at either the vinylpalladium or the product stage. When dibenzoxapine 1a was stirred under the reaction conditions overnight, no isomerization was observed. Therefore, we suspected that isomerization occurred at the vinylpalladium stage under condition A.
24. Examination of alternative ethylboronic acid and n-propylboronic acid mediated reaction conditions also revealed poor results.
25. For substrate 15, replacing methylboronic acid with trimethylboroxine reduced the amount of direct coupling byproduct 11. For aryl iodide substrates 8a-e, <2% of direct coupling products were formed under our optimized conditions and very similar results were obtained when trimethylboroxine was used to replace methylboronic acid.