A synthesis of (−)-tashiromine and formal synthesis of (+)-tashiromine utilizing a highly enantioselective pyrrole/cobaloxime π-cation cyclization

Gage, Jennifer L.; Branchaud, Bruce P.

doi:10.1016/s0040-4039(97)01638-9

Cited by 51 publications

(19 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lithium aluminium hydride reduction of crude 10 provided tashiromine (1) in 36% yield over the two steps. The spectral data were in accord with those reported in the literature [7][8][9][10][11][12][13][14][15][16][17] In summary, we have developed a six-step synthesis of tashiromine from succinimide (19% overall yield). The key finding in this synthesis is that olefin cross-metathesis is a useful route to nitrogen-containing functionalised allylsilanes.…”

Section: Methodssupporting

confidence: 84%

A Concise Synthesis of Tashiromine

McElhinney¹,

Marsden²

2005

Synlett

View full text Add to dashboard Cite

A concise (six-step) synthesis of the indolizidine alkaloid tashiromine (1) has been achieved. Olefin cross-metathesis was used to prepare a key functionalised allylsilane, which subsequently underwent electrophile-induced ring-closure to establish the bicyclic framework with complete control of stereochemistry.Functionalised allylsilanes have been much used in the stereoselective construction of a variety of carbocyclic and heterocyclic structures. 1 Our own group 2,3 and others 4 have been interested in the use of olefin metathesis for the efficient construction of functionalised allylsilanes. To date our own studies have focused on the synthesis of oxygen-containing allylsilanes by ring-closing olefin metathesis 5 and the application of these entities in the stereocontrolled construction of tetrahydrofuran 2 and aryltetralin skeleta. 3 We now wish to report our first ventures into the synthesis of nitrogen containing allylsilanes by olefin cross-metathesis in the context of a short total synthesis of tashiromine (1). Figure 1Alkaloids containing the indolizidine skeleton have diverse biological activity and remain popular targets for synthetic chemists. 6 Tashiromine (1), 7 for example, has been the subject of ten different total syntheses to date (Figure 1). [8][9][10][11][12][13][14][15][16][17] We considered that 1 could be accessed from an intermediate 2 which would be prepared by the intramolecular trapping of an acyl iminium ion 3 by the pendant allylsilane (Scheme 1). In fact, reactions of this type have been developed by Hiemstra and Speckamp, 18 and cyclisation of allylsilane (Z)-4 has been shown to proceed with perfect stereocontrol for the formation of the required trans-stereochemistry. Hiemstra's synthesis of 4 involved alkylation of succinimide with allylsilane-containing mesylate 5a, prepared in four steps from commercially available iodomethyltrimethylsilane and 2-(4-pentynyloxy)tetrahydropyran. Compound 5a and the corresponding iodide 5b have been much employed (both as electrophiles and sources of nucleophiles) in the synthesis of functionalised allylsilanes, and can also be accessed by Wittig reactions using the Seyferth-Fleming phosphorane 19 and nickel-catalysed 1,2-metallate rearrangement of 2-dihydropyranyllithium. 20 We considered that a shorter, more economical 21 and convenient approach to 4 would involve the olefin cross-metathesis of (4-pentenyl)succinimide with the commercially available allyltrimethylsilane (6). 22 Such an approach would have broad applicability well beyond the current investigation and we therefore set about demonstrating its viability. We report herein the successful attainment of this goal. Scheme 1Alkylation of the sodium salt of succinimide with 4-pentenyl bromide gave our metathesis substrate 7 in 98% yield (Scheme 2). Olefin cross-metathesis of 7 with 6 mediated by Grubbs' second generation metathesis catalyst [(H 2 Imes)(Pcy 3 )Cl 2 Ru=CHPh] gave the desired allylsilane 8 in 73% yield as a 3:1 mixture of E-and Z-isomers.

show abstract

Section: Methodssupporting

confidence: 84%

A Concise Synthesis of Tashiromine

McElhinney¹,

Marsden²

2005

Synlett

View full text Add to dashboard Cite

show abstract

“…(−)-Tashiromine has been accessed through the ring closure of difunctionalized acyclic chiral sulfonamide-based β-amino acids [35], the cyclization of pyrrole derivatives with a chiral side-chain [36], or the enantioselective arylation of pyrrole, followed by saturation [37]. The transformation of chiral functionalized pyrrole or pyrrolidine derivatives has served as the basis of the construction of (−)-epitashiromine [38–39] (Fig.…”

Section: Introductionmentioning

confidence: 99%

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Kiss¹,

Forró²,

Fülöp³

2015

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…143 The optically pure cobaloxime complex 6.357, generated from the corresponding alcohol 6.356, was directly trapped by the pyrrole with overall retention of stereochemistry. 143 The optically pure cobaloxime complex 6.357, generated from the corresponding alcohol 6.356, was directly trapped by the pyrrole with overall retention of stereochemistry.…”

Section: Cobaloxime -Cationsmentioning

confidence: 99%

Electrophilic Alkene and Alkyne Complexes

Bates

2012

Organic Synthesis Using Transition Metals

View full text Add to dashboard Cite

A synthesis of (−)-tashiromine and formal synthesis of (+)-tashiromine utilizing a highly enantioselective pyrrole/cobaloxime π-cation cyclization

Cited by 51 publications

References 24 publications

A Concise Synthesis of Tashiromine

A Concise Synthesis of Tashiromine

Novel stereocontrolled syntheses of tashiromine and epitashiromine

Electrophilic Alkene and Alkyne Complexes

Contact Info

Product

Resources

About