Synthesis of steganone

The asymmetric total synthesis of (-)-steganone (67) was achieved through the asymmetric Mg-mediated coupling of bromide 64 and oxazoline 65, which provided a... 

In addition to the simple substitutions shown in Scheme 1, this reaction has been used in a variety of complex systems as a route to optically active substances. For example, use of chiral oxazolines in this coupling process has led to an asymmetric synthesis of (-)-steganone,3 podophyllotoxin,4 (-)-schizandrin,5 and (+)-phylictralin.6 The synthesis of (-)-schizandrin is sketched in Scheme 2. 

The malic acid-derived auxiliary which gives good results in the ferrocene series also looks promising among the chromium complexes, and the six-membered acetal of 400 is much more easily hydrolysed than the tartrate-derived acetals of Scheme 164 . Lithiation and bromination of 400 gives, after hydrolysis of the acetal, the complex 401 in 90% ee, increasing to >99% after recrystallization (Scheme 165). 401 is an intermediate in a formal synthesis of (—)-steganone (Scheme 182, Section III.B.2.b). 

Third, the procedure described above has been applied to the preparation of various biaryls containing hetero-aromatic rings (Entries 15-17, 19, 20). Although the number of papers reporting the use of the Ni- or Pd-catalyzed procedure for aryl-aryl coupling 1s still small, the synthesis of steganone by Raphael and his co-workers is demonstrative of its synthetic potential. 

In their total synthesis of ( )-steganone, Magnus and co-workers solved this problem via the stereoconvergent synthesis of the bicyclo[5.1.0] intermediate 106, Fig. (23) [127,128]. 

An original diastereoselective approach to the synthesis of steganone analogues was reported by Motherwell and co-workers, Fig. (29) [144], The diyne 135 was obtained from bromide 133 and lactone 134 via diastereoselective alkylation and deprotection of the alkyne groups. A cobalt-mediated [2+2+2] cycloaddition of 135 with... 

Luckily, reaction of ( )-picrosteganone under base-promoted conditions (NaOAc in EtOH) provided ( )-steganone in a 90% yield (Eq. 19). Overall, the racemic synthesis of steganone was achieved quite efficiently in 6 steps from known compounds. 

It was at this point that Magnus Ronn and Yvan LeHuerou assumed their roles as postdoctoral associates in our laboratories and worked to eomplete the enantioselective total synthesis of (-)-steganone. To obtain the more reactive benzyl bromide coupling partner in the enantioselective synthesis, methanesulfonic anhydride was required to avoid formation of... 

In addition, intermediate 300, produced using Uemura s methodology, was used in another very elegant synthesis of (-)-steganone (7) by Mo lander and co-workers, Scheme (46) [117]. The primary alcohol of 300 was converted into the corresponding bromide 304 by utilizing... 

---