Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• centres on the stereoselective construction of the indolizidine core by capture of an electrophilic acyliminium species by a pendant allylsilane. The key cyclisation precursor is constructed using olefin cross-metathesis chemistry, which has the potential to facilitate both racemic and asymmetric

• approaches, depending upon the choice of the allylsilane metathesis partner. Results The use of the allyltrimethylsilane cross-metathesis approach enables the rapid construction of the key cyclisation precursor 3 (3 steps from commercial materials), which undergoes acid-induced cyclisation to give the

• and their cross-metathesis reactions studied as part of a putative asymmetric approach to tashiromine. In the event, α-hydroxysilane 12 underwent isomerisation under the reaction conditions to acylsilane 17, while silanes 14 and 15 were unreactive towards metathesis. Conclusion A concise

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

• Annabella F. Newton,
• Martin Rejzek,
• Marie-Lyne Alcaraz and
• Robert A. Stockman

Beilstein J. Org. Chem. 2008, 4, No. 4, doi:10.1186/1860-5397-4-4

• -hippodamine are presented which are able to shorten the syntheses by up to two steps. Conclusions Key advances include a two-directional homologation by cross metathesis and a new tandem reductive amination / double intramolecular Michael addition which generates 6 new bonds, 2 stereogenic centres and two

• symmetrical dialkene similar to 4 using cross-metathesis with acrylonitrile was possible using the Hoveyda modification of Grubbs second generation catalyst [12] (Scheme 2). Thus, it seemed a logical extension of this thinking to see if we could carry out a direct double homologation of dialkene 4 with ethyl

• acrylate as the cross-metathesis coupling partner. In fact, due to the non-co-ordinating nature of ethyl acrylate (in comparison to acrylonitrile) and the inert phthalimide group, this reaction proved to be an outstanding success, delivering diester 6 in 88% yield over one step after a five day reaction in

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

• Wolfgang Maison,
• Marina Büchert and
• Nina Deppermann

Beilstein J. Org. Chem. 2007, 3, No. 48, doi:10.1186/1860-5397-3-48

• , if the generated exocyclic double bond in the RORCM product is susceptible to olefin cross metathesis with the small amount of styrene that is derived from the precatalyst 1. These types of products are favored, if additional olefins are added as CM partners. With addition of 3 equivalents styrene

• and 12. A sequence of ring opening and cross metathesis is extremely efficient for desymmetrization of 7 and 12 as depicted in Scheme 4 for the synthesis of isoindole 19 and the disubstituted pyrrolidine 20. In these cases, catalyst loadings can be low and yields are excellent. Unfortunately the ROCM

• of 7-azabicycloalkenes appeared to be quite sensitive with respect to the olefin cross metathesis partner [67] and we have not been able to transfer this reaction to α-substituted olefins like 21 yet. A more successful attempt to introduce selectivity, was the enantioselective catalytic