Tactics for probing aryne reactivity: mechanistic studies of silicon–oxygen bond cleavage during the trapping of (HDDA-generated) benzynes by silyl ethers

Abstract

We report mechanistic aspects of the trapping of thermally (HDDA) generated benzyne derivatives by pendant silyl ether groups, which results in net insertion of the pair of benzyne Csp-hydribized carbon atoms into the silicon–oxygen sigma bond. Cross-over experiments using symmetrical, doubly labeled bis-silyl ether substrates established that the reaction is unimolecular in nature. Competition experiments involving either intramolecular or intermolecular dihydrogen transfer clock reactions (from within a TIPS isopropyl group or cyclooctane, respectively) vs. the silyl ether cyclization were used to gain additional insights. We evaluated effects of the steric bulk of the silyl ether trapping group and of the ring-size of the cyclic ether being formed (furan vs. pyran). These types of competition experiments allow the relative rates of various product-determining steps to be determined. This previously has only rarely been possible because aryne formation is typically rate-limiting, making it challenging to probe the kinetics of subsequent trapping reactions. Solvent effects (polarity of the medium) and computational studies were used to probe the question of stepwise vs. concerted pathways for the Si–O insertion.

Direct observation ofo-benzyne formation in photochemical hexadehydro-Diels–Alder (hν-HDDA) reactions

“…This latter reaction is now known as a "hexadehydro-Diels-Alder" (HDDA) reaction so named by the Hoye group in 2012 as a logical extension of the dehydro-Diels-Alder reaction. 12 Instead of forming cyclohexene derivatives, the HDDA reaction [13][14][15][16] is believed to produce a highly reactive o-benzyne intermediate, and is of much current interest due to its unusual reactivity/mechanism [17][18][19][20][21][22][23][24][25][26][27] and numerous applications in synthetic chemistry. [28][29][30][31][32][33][34][35] A series of reports within the last three years, [36][37][38][39][40][41][42][43] examining the HDDA reaction from a more mechanistic viewpoint, demonstrate the immense versatility of HDDA-generated o-benzynes, including reaction with an alkyne forming a highly reactive benzocyclobutadiene 21 or reaction with electron-decient thioamides giving stabilized ammonium ylides in a new type of [3 + 2]-cycloaddition.…”

Mechanistic Duality in Tertiary Amine Additions to Thermally Generated Hexadehydro-Diels–Alder Benzynes

“…The benzynes generated by this hexadehydro-Diels–Alder (HDDA) reaction are produced in the absence of the reagents and byproducts that necessarily accompany many of the now-classical methods of aryne generation. This has provided the opportunity to gain new mechanistic understanding of the inherent reaction pathways of certain aryne trapping reactions . Capitalizing on this feature, we have studied and report here mechanistic details concerning the reactions of tertiary amines with HDDA benzynes.…”

Rates of Hexadehydro-Diels–Alder (HDDA) Cyclizations: Impact of the Linker Structure

“…The half-life for the Stage 1 cyclization, the rate-limiting step for all of these unimolecular isomerizations, was determined for each substrate. For the sake of consistency, the same β-( tert -butyldimethylsilyloxy)ethyl moiety was used as the internal trapping group 4 (cf. 5 to 6 ) for each substrate.…”

“… a Yields represent material following chromatographic purification and are from experiments performed on scales of 20–40 mg of substrate in 1,2-DCE for 17 , CDCI 3 for 18 , 4 and o -DCB for 19 . …”