Asymmetric Pauson−Khand Reactions Using Camphor-Derived Chelating Thiols as Chiral Controllers

Abstract

A convenient procedure for the preparation of enantiopure 10-(R-thio)-2-exo-bornanethiols from (1S)-camphor-10-thiol has been developed. The ethynyl derivatives of these thiols gave excellent diastereoselectivities (up to 98:2) in Pauson-Khand reactions with norbornene and norbornadiene through the intermediacy of a chelated dicobalt pentacarbonyl complex. Thermal reaction conditions starting from the preformed chelated complex gave better results than N-oxide-promoted runs with in situ generation of the chelated intermediate. The corresponding adducts have been elaborated through a protocol consisting of conjugate addition, samarium iodide-promoted cleavage of the chiral auxiliary, and retro-Diels-Alder reaction to afford 4-substituted 2-cyclopentenones in high enantiomeric purity.

Synthesis of Chiral Cyclopentenones

“…Marchueta et al have developed a convenient procedure for the preparation of enantiopure 10-( R -thio)-2- exo -bornanethiols 153 from (1 S )-camphor-10-thiol 152 (Scheme ). Their ethynyl derivatives 154 led to excellent diastereoselectivities (up to 98:2) in Pauson–Khand reactions with norbornene and norbornadiene through the intermediacy of a chelated dicobalt pentacarbonyl complexes 155 . It was found that thermal reaction conditions starting from the preformed chelated complexes were more efficient than N -oxide-promoted runs with in situ generation of the chelated intermediates.…”

Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes

“…So far, the use of thioalkynes in [3+2] annulations has not been reported, although they have been successfully applied in [4+2],– [3+2] and [2+2]– cycloadditions as well as in the Pauson–Khand reaction . Only two examples of [3+2] annulations of thioalkynes were reported, but none of them was based on the use of DA cyclopropanes .…”

The Pauson–Khand reaction, a powerful synthetic tool for the synthesis of complex molecules

“…6). 43 These chiral auxiliaries act by transmitting their chirality to the metal cluster due to the chelation with a cobalt atom, which upon diastereoselective complexation of the olefin, controls the absolute configuration of the final cyclopentenone (Fig. 7).…”

“…The chiral auxiliary is eliminated using samarium iodide, and a retro-Diels-Alder reaction can finally afford highly enantiomerically enriched 4-substituted cyclopentenones (Scheme 34). 43 Carretero has demonstrated the feasibility of carrying out the PKR with electron deficient olefins. Among the different electronic withdrawing groups used by this group, chiral sulfoxides attached Fig.…”