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. 2016 Dec 19;55(51):15920-15924.
doi: 10.1002/anie.201609598. Epub 2016 Nov 16.

Short Enantioselective Total Synthesis of Tatanan A and 3-epi-Tatanan A Using Assembly-Line Synthesis

Adam Noble  1 , Stefan Roesner  1 , Varinder K Aggarwal  1
Affiliations

Short Enantioselective Total Synthesis of Tatanan A and 3-epi-Tatanan A Using Assembly-Line Synthesis

Adam Noble et al. Angew Chem Int Ed Engl. .

Abstract

Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly-line synthesis approach, using iterative lithiation-borylation reactions, was applied to install the three contiguous stereocenters with high enantio- and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate-controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps.

Keywords: Matteson homologation; alkynylation; lithiation-borylation; tatanan A; total synthesis.

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Figures

Figure 1
Figure 1
A) Iterative homologation of boronic esters. B) Natural products with alkyl‐ and aryl‐substituted carbon chains. C) Use of primary benzyl benzoates in homologation of boronic esters.
Scheme 1
Scheme 1
Retrosynthetic analysis of tatanan A.
Scheme 2
Scheme 2
Synthesis of secondary alkyl boronic ester 10. NIS=N‐iodosuccinimide; neo=neopentyl glycolato; TIB=2,4,6‐triisopropylbenzoyl.
Scheme 3
Scheme 3
Alternative strategy for the third homologation. A) Plausible mechanism for high diastereoselectivity in homologations of 10 with 9. B) Proposed diastereoselective Matteson homologation. C) Optimized conditions for reversal of diastereoselectivity. Ar=2,4,5‐trimethoxyphenyl; LDA=lithium diisopropylamide.
Scheme 4
Scheme 4
Total synthesis of tatanan A and 3‐epi‐tatanan A. Ar=2,4,5‐trimethoxyphenyl. Cb=N,N‐diisopropylcarbamoyl.
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