Vinyl sulfoxides as stereochemical controllers in intermolecular Pauson-Khand reactions: applications to the enantioselective synthesis of natural cyclopentanoids.
The use of sulfoxides as chiral auxiliaries in asymmetric intermolecular Pauson-Khand reactions is described. After screening a wide variety of substituents on the sulfur atom in alpha,beta-unsaturated sulfoxides, the readily available o-(N,N-dimethylamino)phenyl vinyl sulfoxide (1 i) has proved to be highly reactive with substituted terminal alkynes under N-oxide-promoted conditions (CH3CN, 0 degrees C). In addition, these Pauson-Khand reactions occurred with complete regioselectivity and very high diastereoselectivity (de=86->96 %, (S,R(S)) diastereomer). Experimental studies suggest that the high reactivity exhibited by the vinyl sulfoxide 1 i relies on the ability of the amine group to act as a soft ligand on the alkyne dicobalt complex prior to the generation of the cobaltacycle intermediate. On the other hand, both theoretical and experimental studies show that the high stereoselectivity of the process is due to the easy thermodynamic epimerization at the C5 center in the resulting 5-sulfinyl-2-cyclopentenone adducts. When it is taken into account that the known asymmetric intermolecular Pauson-Khand reactions are limited to the use of highly reactive bicyclic alkenes, mainly norbornene and norbornadiene, this novel procedure constitutes the first asymmetric version with unstrained acyclic alkenes. As a demonstration of the synthetic interest of this sulfoxide-based methodology in the enantioselective preparation of stereochemically complex cyclopentanoids, we have developed very short and efficient syntheses of the antibiotic (-)-pentenomycin I and the (-)-aminocyclopentitol moiety of a hopane triterpenoid.
Rodríguez Rivero
Marta
M
Departamento de Química Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Alonso
Inés
I
Carretero
Juan C
JC
D000480:Alkynes / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry; D018360:Crystallography, X-Ray; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism; D013454:Sulfoxides / Q000138:chemical synthesis / Q000737:chemistry*; D014315:Triterpenes / Q000138:chemical synthesis; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D000480:Alkynes; D000900:Anti-Bacterial Agents; D001688:Biological Products; D003517:Cyclopentanes; D013454:Sulfoxides; D014315:Triterpenes; D014753:Vinyl Compounds; D003035:Cobalt; C008792:pentenomycin I; C054760:32,33,34,35-bacteriohopanetetrol