Vinyl Sulfoxides as Stereochemical Controllers in Intermolecular Pauson–Khand Reactions: Applications to the Enantioselective Synthesis of Natural Cyclopentanoids

Abstract

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.

Photochemical halogen-bonding assisted generation of vinyl and sulfur-centered radicals: stereoselective catalyst-free C(sp2)–S bond forming reactions

“…In order to prove the usefulness of our reaction, we searched for synthetic applications of our compounds. Given the importance of vinyl sulfoxides and sulfones in naturally occurring molecules 27 and as valuable building blocks in organic synthesis, 28 we looked for conditions to oxidize the vinyl sulfides to both of these molecules (Scheme 7a). In this regard, starting from the vinyl sulfide 3aa , we optimized a procedure 29 which employs m CPBA as an oxidant for the obtention of the corresponding vinyl sulfoxide 14 , which was delightfully furnished in our case with a 100 : 1 trans / cis diastereomeric ratio.…”

A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates—Bioinspired Sulfoxidation Catalysts

“…Alkylating agents 4-bromobut-1-yne [44] and 5-bromopent-1-yne [45,46,47], and alloxazines 3-methylalloxazine [48] and 1-methylalloxazine [31] were prepared according to previously published procedures.…”

The Intermolecular Pauson‐Khand Reaction: Applications, Challenges, and Opportunities

“…Although numerous examples of alkenes with coordinating ancillary groups have been described, [26] the state‐of‐the‐art is defined by the (2‐dimethylaminophenyl)‐sulfoxide group developed by Carretero (Table 1), which furnishes good yield with a range of different alkyne components [26c,d] …”