Transition-Metal-Free Carbofluorination of TBS-Protected Nitrogen-Containing Cyclic Enynols: Synthesis of Fluorinated Azabicycles

Abstract

The synthesis of fluorinated azabicycles from tert-butyldimethylsilyl-protected N-containing cyclic enynols using inexpensive BF3·OEt2 is described. In this reaction, BF3 reacts as both the Lewis acid and the fluoride source for cyclization/fluorination of the TBS-protected cyclic N-containing enynols. The method provides an easy access to fluorinated azabicycles where a new C(sp(2))-F bond and a new bicyclic skeleton are generated at ambient temperature within 1-13 min under metal-free reaction conditions.

Convenient Synthesis of (E)‐5‐Aryl(halo)methylenebicyclo‐ [2.2.2]oct‐2‐enes and ‐[2.2.1]hept‐2‐enes via Lewis Acid‐ Promoted Carbohalogenation of Cyclic 2,6‐Enynols

“…instantaneously under air at ambient temperature to afford the desired carbofluorination products 5a – e in good yields and with high E/Z selectivities (Scheme ). The success of using the TBS‐protected 2,6‐enynols with BF 3 ⋅OEt 2 for carbofluorination is consistent with our previous results 9a…”

“…Another method involved a zinc halides‐catalyzed cycloaddition of propargyl halides with cyclopentadiene, producing the 5‐[aryl(halo)methylene]bicyclo[2.2.1]hept‐2‐enes in low yields 8. Based upon our previous experience with Lewis acid‐promoted carbohalogenations of C‐2 and C‐3 propargyl‐tethered cyclic 2‐enols providing fused9a and spiro bicycles,9b respectively, we anticipated that cyclic 2‐enols bearing a 3‐arylpropargyl tether at the C‐4 position of the ring may alter the reaction path and lead to bridged bicyclic skeletons bearing an exo ‐methylene group. Herein, we describe a Lewis acid‐promoted carbohalogenation of cyclic C‐4‐(3‐aryl‐prop‐2‐ynyl)‐tethered 2‐enols to generate bridged bicyclic compounds having an ( E )‐aryl(halo)methylene group at the C‐5 position.…”

Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins

“…Among them, there are few reports on the synthesis of mono-fluorinated bicycles by different fluorinating reagent-promoted intramolecular tandem cyclization/fluorination processes, as shown in Scheme 1. [14][15][16][17][18][19][20][21] These elegant synthetic routes have exhibited some advantages, including easy operation, high sitespecific selectivity, and optimal reaction conditions.…”

“…For the involvement of boron trifluoride etherate, Yeh et al demonstrated that transition-metal-free carbofluorination of TBS-protected cyclic enynols provided bicyclic octahydroisoquinolines. 14 Wang et al investigated the synthesis of fluorinated azaheterobicycles via NIS-mediated iodina-tion of 4-alkenamine followed by aminocyclization of amino group with in situ formed iodonium ion. 16 Cheng et al explored the possibility of Selectfluor-mediated efficient installation of the primary fluoro group on a benzo[d]oxazine skeleton via fluorocyclization of o-styryl benzamides.…”

Functionalization of Alkynes for Preparing Alkenyl Fluorides

“…In 2013 Yeh and coworkers accomplished the synthesis of fluorinated azabicycles via a carbofluorination of TBS (tert- (Fig. 17) [38]. Interestingly, the azabicyclic products were highly structurally dependent on the starting enynols.…”