Abstract
Herein, we describe a two-step ring expansion of 1-indanones to afford 2-chloro/bromo-1-naphthols (32 examples). The developed method shows broad functional group tolerance, benefits from mild reaction conditions, and enables rapid access to the tetracyclic core of gilvocarcin natural products. The orthogonally functionalized products allow for selective postmodifications as exemplified in the total synthesis of defucogilvocarcin M. For the selective oxidation of the chromene, a mild and regioselective oxidation protocol (DDQ and TBHP) was developed.
Highlights
We describe a two-step ring expansion of 1-indanones to afford 2-chloro/bromo-1-naphthols (32 examples)
The potent biological activities associated with these structures as well as their use in asymmetric catalysis have attracted a great deal of attention for the development of efficient methods for their synthesis.[8]
Other protocols are based on sensitive and uncommon intermediates or reagents.[13]. They suffer from noncommercial starting materials, preventing rapid access to structurally diverse analogues
Summary
CHBr3 (equiv) 2.2 2.2 5.0 2.0 2.0 base addition at −78 °C at 23 °C at 23 °C at 23 °C at −78 °C. After a survey of alternative methods, Lipshutz’s Cu(I)-mediated biaryl coupling protocol (t-BuLi, CuCN· 2LiX) evolved as the first solution for obtaining the full skeleton of 45 (procedure a).[30] When an excess of t-BuLi (11 equiv) was used, simultaneous removal of the benzyl group took place to form 41b, sparing an additional deprotection step (procedure b).[31] Prolonged treatment with 1,3-dinitrobenzene (>1.5 h) led to overoxidation and opening of the lactone ring (not shown). We were pleased to see that this transformation could be applied in a one-pot fashion affording isopropylated defucogilvocarcin M (43) in 85% yield These conditions were completely selective for the chromene core in the presence of a benzyl group (44) and tolerated the free hydroxyl group of naphthol 41b to directly give defucogilvocarcin M (45) in 80% yield.
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