Alkynyl borones

In contrast to the thermal reactions of 1-alkynylboronic esters, the cycloaddition smoothly takes place under very mild conditions in the presence of metal catalysts (Scheme 28). A cobalt(i) complex catalyzed the [4+2]-cycloaddition of alkynyl boronates with 1,3-dienes to give cycloalkenyl boronates 266431 and with ct,cu-diynes giving arylboronates... 

Alkenylboronic acids and esters underwent conjugated addition to ct,/ -unsaturated ketones in the presence of trifluoroborane etherate589 or cyanuric fluoride (Equation (129)).590,591 Alkadienyl trifluoromethyl ketones were stereoselectively prepared from (2-alkoxyvinyl) trifluoromethyl ketones (Equation (130)).592 Alkynyl boronates can transfer the alkynyl groups regioselectively and enantioselectively to enones (Equation (131 )).593... 

Not until 2005 were the first organoboron derivatives of pyridazines reported in the literature [57]. Harrity reported the preparation of pyridazin-4-ylboronic esters (99) via cycloaddition of tetrazines (98) with alkynyl boronic esters. Some of these boronic sters have been used in Suzuki reactions with iodobenzene. Although the organoboron compounds 99 are electron deficient (and some are also sterically hindered) protodeboronation usually proved no major problem. 

Another example of inverse-electron demand reactions of 3,6-disubstituted 1,2,4,5-tetrazines is with alkynyl boronic esters which provides a direct and regioselective method for the synthesis of pyridazine boronic esters <05AG(E)3889>. 

Pyridazin-4-ylboronates are available via Diels-Alder reactions of alkynyl boronates and 1,2,4,5-tetrazines, and the 4-stannanes similarly from l,2,4-triazines and l,2,4,5-tetrazines. ° The stannylpyr-idazine, without other substituents, can also be obtained by this latter method, as shown below. " ... 

Pyrone reacts readily as a diene in Diels-Alder additions, but the initial adduct often loses carbon dioxide, generating a second diene that then adds a second mole of the dienophile reaction with maleic anhydride, shown below, is typical - a monoadduct can be isolated, which under more vigorous conditions loses carbon dioxide and undergoes a second addition. When the dienophile is an alkyne, methyl propiolate for example, benzenoid products result from the expulsion of carbon dioxide. Primary adducts, which have not lost carbon dioxide, can be obtained from reactions conducted at lower temperatures under very high pressure or in the presence of lanthanide catalysts. A useful example is the reaction of 2-pyrone and substituted derivatives with alkynyl boronates leading to aryl boronates 2-pyrone itself reacts in 86% yield with trimethylsilylethynyl boronate. ... 

Piperine was recently synthesized using a palladium catalyzed coupling of an ( )-p-bromoacrylamide with an alkynyl boronate [398]. A peroxidase catalyzed regioselective epoxidation of the C(2)-C(3) double bond in 121 has been described [399],... 

Pyridazine boronic esters are substrates in Suzuki cross-coupling reactions. [4-I-2] Cycloaddition reactions of 1,2,4,5-tetrazine derivatives 1 with alkynyl boronic esters 257 provide easy access to functionalized pyridazine boronic esters 258. New unsymmetrical 1,2,4,5-tetrazines 259 and 261 have been prepared and tested in reactions with alkynyl boronic esters 257, providing the corresponding pyridazines 260 and 262 as single regioisomers (Scheme 64) <2005AGE3889>. 

Amslinger S, Aubert C et al (2008) Cobalt-mediated [2+2+2] cycloaddition of alkynyl boronates to indole and pyrrole double bonds. Synlett 2056-2060... 

A few studies have been carried out on coupling of alkynyl borones. The stable methoxy(alkynyl)borate complex 158 was prepared in situ by the treatment of B-methoxy-9-borabicyclo[3.3.1]nonane (157) with alkynyllithiums or potassium reagents, and used directly for the coupling with halides to afford a variety of the disubstituted alkynes sueh as 159 [72,73]. 

In this field, interesting examples have been disclosed by Hilt and coworkers, who, based on their pioneering woik of cobalt(I)-catalyzed Diels-Alder reaction anploying alkynyl boron derivatives and 1,3-dienes for the generation of dihydroaromatic building blocks [3], have recently explored more complex procedures with the presence of four components (Schemes 4.1 [4] and 4.2 [5]). 

In this first example, a cobalt(I)-catalyzed Diels-Alder reaction employing alkynyl boron derivatives 2 and 1,3-diene 1 for preparation of dihydroaromatic building blocks 4 is disclosed. Ensuing, dihydroaromatic boronic ester intermediates 3 were used as useful synthetic scaffolds in an unusual thermal Diels-Alder reaction with different dienophiles, generating highly substituted and functionalized products in acceptable to very good yields by recrystallization after four synthetic steps. Five new C—C bonds from four simple components were formed in this process. 

The Schaus group also reported related reactions involving asymmetric allyl-boration of acyl imines [59], asymmetric three component Petasis condensation reaction of secondary amines/glyoxylates/alkenyl boronates [60], as well as addition of aryl, vinyl, and alkynyl boronates to acyl imines (Fig. 15) [61]. In the later reaction, a two point coordination transition state was proposed to account the observed facial selectivity. 

The same year, Gandon et al. reported the synthesis of fused arylboronic esters 36 via cobalt(0)-mediated cycloaddition of alkynylboronates 33 with diynes 35 (Scheme 1.11) [22], The boronate is first reacted with Co2(CO)g at room temperature for 4 h to generate the corresponding dicobaltatetrahedrane 34. The diyne is then added and the mixture is refluxed for 2 h. To show the utility of the products, one of them was treated with phenyl iodide under Pd catalysis to give 37. Complementary to these investigations, Ru-catalyzed [2 - - 2 - - 2] cycloaddition of tethered alkynyl-boronic esters with alkynes was reported [23]. In this case, the borylated arene could not be isolated but was converted directly in situ by Suzuki-Miyaura coupling. 

The alkynyl-boron derivatives were also used to generate a variety of pinacolboron-functionalized arenes via a Diels-Alder reaction (Scheme 13.11) [12]. In this case the DDQ oxidation strategy (e.g., for 21) proved to be superior to the cycloaddition/elimrnation strategy to afford products such as 20. This is based mostly on the problems associated with the synthesis of a broad variety of 1-thiophenyl-substituted 1,3-dienes (X = S) as well as on the reduced reactivity of those dienes in cobalt-catalyzed Diels-Alder reactions. 

The application of alkynyl boron derivatives in cobalt-catalyzed Diels-Alder reactions was used by Hilt et al. for the synthesis of boron-functionalized cycloadducts such as 41, generated from 17 and isoprene under cobalt catalysis (Scheme 13.21). In a four-component reaction sequence, 41 could be converted in a thermal Diels-Alder reaction with dienophiles, such as A-phenylmaleimide, to form the tricyclic product 42 [26],... 

The intramolecular diyne intermediate A formed in situ from alkynyl-boronate 2.144 and propargyl alcohol 2.145 forms metallocycle 2.146 with the catalyst [Cp RuCl (cod)]. The regioselective addition of the ruthenacycle 2.146 to the terminal alkyne 2.147 results in formation of arylboronate B. The latter without isolation undergoes further functionalization to form substituted biphenyl 2.148 in a satisfactory yield. 

Scheme 3.73 Synthesis and reactions of functionalized alkynyl boronic derivatives.

Alkynyl boronic acid derivatives were not used earlier in Suzuki couplings. An effective Suzuki-Miyaura reaction between alkynyl ate complexes (alkynyltrialk-oxy borate complexes) has been reported by Colobert [112] Oh [113]. 1-Alkynyl(trii-sopropoxy) borates (137) were prepared by borylation of the corresponding alkynyl lithium species. These stable borate complexes were subsequently used in Suzuki coupling leading to products of type 138 (Scheme 3.74). 

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