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. 2015 Jun 1;6(6):3599-3605.
doi: 10.1039/c5sc00338e. Epub 2015 May 5.

Enantioselective and diastereoselective azo-coupling/iminium-cyclizations: a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B

Qi Li  1   2 , Tingting Xia  2 , Licheng Yao  2 , Haiteng Deng  3 , Xuebin Liao  2
Affiliations

Enantioselective and diastereoselective azo-coupling/iminium-cyclizations: a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B

Qi Li et al. Chem Sci. .

Abstract

We report a unified strategy for the total syntheses of (-)-psychotriasine and (+)-pestalazine B based on the advanced intermediates of 3α-amino-hexahydropyrrolo[2,3-b]indole. To construct these structural motifs, a cascade reaction involving a BINOL-derived phosphoric anion-paired catalyst for enantioselective or diastereoselective azo-coupling/iminium-cyclizations was developed. The remaining key steps of the synthesis involve a sterically hindered amination via hypervalent iodine reagents and the Larock annulation. These transformations enable a general approach to the syntheses of indole alkaloids containing a 3α-amino-hexahydropyrrolo[2,3-b]indole motif and could be further applied to build a natural product-based library.

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Figures

Fig. 1
Fig. 1. Compounds containing the 3α-amino-hexahydropyrrolo[2,3-b]indole core.
Fig. 2
Fig. 2. Reported synthetic methods for the 3α-amino-hexahydropyrrolo[2,3-b]indole core structure (a–e) and our approach in this publication and others (f).
Scheme 1
Scheme 1. Enantioselective azo-coupling of tryptamine derivatives.
Scheme 2
Scheme 2. Retrosynthetic analysis of (–)-psychotriasine (2).
Scheme 3
Scheme 3. Total synthesis of (–)-psychotriasine (2). Reagents and conditions: (a) (i) NaHMDS, Boc2O, THF, –60 °C; (ii) RANEY® nickel, hydrazine hydrate, MeOH, sealed tube, 70 °C, 88% yield over 2 steps; (b). Pd(OAc)2 (0.2 equiv.), xantphos (0.3 equiv.), t-BuONa (2.0 equiv.), toluene, 80 °C, 71% yield; (c) 13, Pd(OAc)2 (0.2 equiv.), DtBPF (0.3 equiv.), K2CO3 (2.5 equiv.), NMP, 110 °C, 83% yield; (d) (i) DIBAL-H (3.0 equiv.), toluene, –78 °C; (ii). ClCO2Me (3.0 equiv.), Na2CO3 (3.0 equiv.), DCM–H2O (2 : 1 ratio), rt, 64% yield over 2 steps; (e) (i) CF3CO2H, DCM, 0 °C; (ii) Red-Al (12.0 equiv.), toluene, reflux, 51% yield over 2 steps. Alkyne 13: N-(methoxycarbonyl)-4-(trimethylsilyl)-3-butynylamine.
Fig. 3
Fig. 3. Thermal ellipsoid plot of the X-ray structure of compound 16 at the 50% probability level.
Scheme 4
Scheme 4. Total synthesis of (+)-pestalazine B (4). Reagents and conditions: (a) PhN2BF4, K2CO3, CPA8a, DCE–THF (1.5 : 1), 0 °C, 79% yield; (b) hydrazine hydrate, Pd/C, EtOH, 85 °C, 80% yield; (c) A3, Cu(OTf)2, Na2CO3, DMF, 65 °C, 45% yield, (d) 21, Pd(OAc)2, DtBPF, Na2CO3, NMP, 80 °C, 57% yield.
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