Repurposing π Electrophilic Cyclization/Dealkylation for Group Transfer

Abstract

A metal-free regio-and stereocontrolled grouptransfer route toward the synthesis of trisubstituted alkenes is described. In this route, an electrophilic heterocyclization is followed by ring-opening group transfer. Specifically, a thioboration reaction transforms readily available alkynyl sulfide precursors into alkenyl boronates and alkenyl sulfides with defined regio-and stereochemistry in one synthetic step using commercially available B-chlorocatecholborane (ClBcat). Mechanistic studies identified the likely pathway as proceeding through zwitterionic rather than haloborated intermediates. The regio-and stereochemistry set in the initial cyclization step is preserved in the final acyclic alkene product, producing alkenes with up to four modifiable substituents with predictable regio-and stereochemistry. Downstream functionalization reactions showcase the versatility of the substitutions of the resulting alkenes. The mechanistic concept maps onto future reaction designs, given the abundance of known electrophiles and nucleophiles for electrophilic heterocyclization/dealkylation sequences.

Iodination–Group-Transfer Reactions to Generate Trisubstituted Iodoalkenes with Regio- and Stereochemical Control

“…Compared to the previously reported borylative-group-transfer reaction, the iodine group-transfer reaction completes more rapidly and at a lower temperature, reflecting similar trends when comparing boron and iodine in traditional (“Larock-type”) electrophilic-cyclization demethylation reactions. For example, an electrophilic-cyclization–demethylation reaction with I 2 to generate 3-iodobenzothiophenes from I 2 proceeded at room temperature in 10 min .…”

“…This structure thus plausibly shows the residual interaction of stabilization of the iodide during electrophilic attack by the second equivalent of I 2 , similar to that attributed to bromonium and Br 3 − in the crystal structure of a bromination intermediate. 37 Compared to the previously reported borylative-grouptransfer reaction, 22 the iodine group-transfer reaction completes more rapidly and at a lower temperature, reflecting similar trends when comparing boron and iodine in traditional ("Larock-type") electrophilic-cyclization demethylation reactions. For example, an electrophilic-cyclization−demethylation reaction with I 2 to generate 3-iodobenzothiophenes from I 2 proceeded at room temperature in 10 min.…”

“…Hept-3-yn-1-yl(p-tolyl)sulfane (4e). 4e was prepared according to a literature procedure 22 in 55% yield on a 0.5 g scale over two steps from 4-methylbenzenethiol and hept-3-yn-1-ol. 1 H NMR (CDCl 3 , 600 MHz): δ 7.30 (d, J = 7.9 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 2.47−2.44 (m, 2H), 2.33 (s, 3H), 2.15−2.13 (m, 2H), 1.55−1.49 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).…”

“…14−21 In previous work, the first example of this electrophilic-cyclization-group-transfer was demonstrated with boron as the electrophile, generating trisubstituted borylated alkenes with regio-and stereocontrol (Scheme 1a). 22 The term "group transfer" in this context refers to the transfer of the SAr group to a different carbon during the reaction. We hypothesized that the mechanistic concept may be applicable to a broader range of electrophiles.…”

“…Diiodinated product 3e (96%) is noteworthy due to its high yields when compared to otherwise similar group transfer reactions attempted with ClBcat, which were lower yielding, presumably due to decomposition of material at the high heat required for the boron-based reaction (120 °C). 22 Product 3g (65%) is notable as benzothiazoles are desirable functionalities in pharmaceuticals. 35 Product 3j (68%) shows that the reaction is compatible with acidic functional groups.…”