Double carbometallation of alkynes: an efficient strategy for the construction of polycycles

Abstract

Cyclization reactions of alkynes, especially the double carbometallation of alkynes, have drawn much interest from organic chemists because of their high efficiency in the construction of polycycles. Utilizing different nucleophiles or catalytic systems, various efficient strategies to access challenging skeletons have been extensively explored in recent years. In this review, achievements in this field are presented in three major parts (the syn-syn, anti-anti, and syn-anti addition reactions of diynes or two alkyne molecules). Cyclization reactions of diynes initiated by nucleophiles, [2+2+n] cycloaddition, or other processes and reactions, involving two identical or different alkynes are described, which provide facile and reliable approaches to various π systems, medium-sized rings, and even macrocycles.

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

“…Loss of H + as HCl then leads to rearomatization, with no competing protodeboronation of the newly formed vinylBCl 2 moiety, which is subsequently pinacol protected. 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 with 1equiv consumed by formation of [(TBP)H][BCl 4 ]).…”

Facile Assembly of Benzo[b]naphtho[2,3‐d]azocin‐6(5 H)‐ones by a Palladium‐Catalyzed Double Carbometalation

“…Recently,t he double carbometalation of alkynesw as reported as an efficient route to polycycles with molecularc omplexity. [4] Usually,e xcellent chemoselectivities and regioselectivities are observed duringt he reaction process. For instance, the palladium-catalyzed carbonylation of 2-alkynylphenols with carbon monoxide usually affords 2-carbonylbenzofurans.…”

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

“…Loss of H + as HCl then leads to rearomatization, with no competing protodeboronation of the newly formed vinylBCl 2 moiety, which is subsequently pinacol protected. 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 …”

“…Furthermore,m etal-free borylative cyclization is distinct from the reactivity of transition metals and heavier group 13 electrophiles (e.g., GaCl 3 ), which catalyze the cycloisomerization of alkynes without concomitant functional-group installation (Scheme 1). [10] Given the ubiquity of alkyne functionalization using boron electrophiles (e.g., hydroboration) the cyclization of unactivated [11] alkynes induced by any boron electrophile is relatively scarce.N oteworthy exceptions use B(C 6 F 5 ) 3 to initiate cyclization, thus generating av ariety of borylated polycyclic structures. [12] Whilst notable,t hese reactions use the expensive (relative to BCl 3 )e lectrophile B(C 6 F 5 ) 3 ,w hich can concomitantly install aC 6 F 5 group,and more significantly, precludes formation of the desirable boronic acid derivatives.…”