A Mechanistic Study of the Lewis Base-Directed Cycloaddition of 2-Pyrones and Alkynylboranes

Abstract

Significant rate enhancements in the Diels-Alder reaction of alkynes and 2-pyrones bearing a Lewis basic group are observed when a combination of alkynyltrifluoroborates and BF 3 .OEt 2 are used. This process generates functionalized aromatic compounds with complete regiocontrol. The origin of the observed rate enhancement has been studied by DFT methods, and they appear to originate for coordination of the diene substrate to a mixture of alkynylborane intermediates, followed by a Lewis acid mediated product equilibration step. Evidence for this mechanism is presented, as is the enhanced promotion of the cycloaddition via the use of alternative Lewis acid promoters.2

Formation of C(sp2)Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

“…[26] Finally,w ei nvestigated whether aB Cl 3 -activated alkyne could be intercepted by an external p-nucleophile,similar to the reactivity observed by combining B(C 6 F 5 ) 3 ,p henylacetylene,a nd N-tBu-pyrrole. [27] 1-Phenyl-1-propyne shows no reactivity with 2-methylthiophene or BCl 3 alone,yet when all three were combined in the presence of TBP,the product (12) from a trans-1,2-carboboration was isolated after esterification in a4 1% yield (Scheme 6). Thus BCl 3 -induced alkyne carboboration is not limited to intramolecular p-nucleophiles.…”

“…[2] Whilst this reaction has developed into atruly powerful transformation, the discovery of new routes,p articularly transition-metal-free methods,t o efficiently generate C(sp 2 ) À boronate esters,w hich are challenging to access by iridium catalysis,r emains desirable. Recent advances in transition-metal-free borylation include benzannulations, [3] radical mediated borylation, [4] electrophilic borylation, [5] and carbanion-mediated borylation. [6] One underexplored approach to metal-free C(sp 2 )ÀB bond formation proceeding from simple hydrocarbon precursors is the borylative cyclization of alkynes,w herein ab oron electrophile activates an alkyne for intramolecular electrophilic cyclization with as econd p-system.…”

“…Theb orylative cyclization of 1a with BCl 3 is distinct to the reactivity of transition metals [10] and heavier group 13 Lewis acids (e.g., GaCl 3 and InCl 3 ), [15] which catalyze the cycloisomerization of similar alkynes (Scheme 1, top). Thed isparity observed between BCl 3 and the heavier group 13 analogues presumably arises from the less polar and stronger BÀCbond (relative to GaÀC), which makes the borylated compounds more resistant to protodemetallation and thus enables isolation of the desired C(sp 2 )Àboronate esters.N otably,p rotodeboronation products are observed as aminor component for anumber of substrates (these may also form by HCl initiated cyclization), but performing the reaction with the hindered base 2,4,6-tritert-butylpyridine (TBP) enables cleaner borylative cyclization (this requires 2equiv of BCl 3 …”

Synthesis, Characterisation and Reactions of Phosphine-Substituted Alkynylboronates and Alkynyltrifluoroborate Salts

“…Preliminary studies towards Lewis acid promoted and directed cycloadditions of 2-pyrones and 1,2,4-triazines [29][30][31] were disappointing, returning protodeborylated alkyne in all cases attempted. However, we were more successful in performing cross-coupling reactions.…”

Competing mechanisms for the reaction of dichloropropynylborane with 2-tert-butylbutadiene. Diels–Alder reaction versus alkynylboration

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Moreover, the cycloaddition products can be used in subsequent reactions to obtain complex structures. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Moreover, the cycloaddition products can be used in subsequent reactions to obtain complex structures.…”