Catalyzed double Michael addition of anilines to vinyl sulfone

Tetrahedron Letters

Volumn 44, Issue 17, 2003, Pages 3459-3462

  Chen, Jiong Jack ^a   Lu, Cuong V ^a   Brockman, Rebecca N ^a  

^a PFIZER INC   (United States)

Author keywords

Catalysis; Michael addition; Thiomorpholine; Vinyl sulfone

Indexed keywords

ALUMINUM CHLORIDE; ANILINE DERIVATIVE; PHENYLTHIOMORPHOLINE DIOXIDE; PHOSPHORIC ACID; SULFONE DERIVATIVE; UNCLASSIFIED DRUG; VINYL DERIVATIVE; VINYLSULFONE;

ARTICLE; CATALYSIS; CATALYST; CHEMICAL STRUCTURE; MICHAEL ADDITION;

EID: 0037459875     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)00702-0     Document Type: Article

References (8)

1. Ford-Moore A.H. J. Chem. Soc. 1949;2433-2440.
2. Straley, J. M.; Fisher, J. G. US Patent No: 3,585,182.
3. Using 1:1 ratio of aniline and vinyl sulfone, Ford-Moore obtained 56% yield of desired 4-phenylthiomorpholine, 1,1-dioxide and 10% yield of 2,2′-dianilinodiethyl sulfone. Using 2:1 ratio, 76% yield of the desired product was obtained. However, for our purpose, neither starting material was cheap, thus 2:1 ratio was not an option. Plus, purification became more challenging if excess aniline was used.
4. Using Lewis acids to catalyze sulfone for other transformations are known, such as Friedel-Crafts reaction: Trost B.M., Matsuoka R.T. Synlett. 1992;27-30.
5. 2 plug (1.8 kg). The column was eluted with methylene chloride (16 L) until clear. The methylene chloride solution was concentrated to give 387 g of compound 3 as light brown solids (68% yield).
6. 4 at room temperature. The mixture was heated to 140°C for 16 h. The resulting suspension was cooled to ∼70°C and poured into 100 mL of water. After cooling to room temperature, the mixture was filtered. The beige solids were washed with water and dried to give 13.2 g (89%) of compound 3 .
7. 2S: C, 42.40; H, 3.20; N, 4.95; S, 11.32; F, 26.83. Found: C, 41.88; H, 3.21; N, 4.69.
8. Several monovinyl sulfones, such as phenyl vinyl sulfone and methyl vinyl sulfone, have been tried under the same conditions. The Michael addition did proceed under catalyzed conditions. However, some Michael addition product continued to the second Michael addition to give a bis-adduct (an adduct derived from one aniline and two monovinyl sulfone). A mixture of products was formed, thus, makes this extended application less useful. Furthermore, the reaction mixture was very obnoxious, suggesting the decomposition of monovinyl sulfones under Lewis acid conditions.