Regio- And Stereoselective Synthesis Of 1,4-Dienylboronates Via Copper-catalyzed Boryl-allylation Of Alkynes

Organoboron compounds are important reagents in organic chemistry enabling many chemical transformations and the development of efficient strategies for the stereoselective synthesis of these compounds is an important goal. Among them, vinylboronates play an important role in organic synthesis due to their utility in the Suzuki-Miyaura coupling reactions and conjugate additions. Metal-catalyzed borylation of alkynes is the most direct way to access these vinylboronic esters. The ?-borylalkenylcopper generated from the syn-addition of borylcopper to alkynes are strong carbon nucleophiles and can be used to couple with various electrophiles to form more complex vinylboronates by concomitant formation of new C?H, C?C or C?heteroatom bonds.Copper-catalyzed tandem reactions among bis(pinacolato)diboron, alkynes, and allyl phosphates produce 1,4-dienylboronates with high degree of chemoselectivity, regioselectivity and stereoselectivity. The 1,4-diene framework is prevalent in bioactive natural products. Through the detailed optimization of reaction conditions, the research results have been achieved as follows:⑴ Using the reaction among phenyl acetylene and allyl phosphate(Z)-2a as a template, We had determine the reaction condition of copper-catalyzed γ-E-selective boryl-allylation among a terminal alkyne and an allyl phosphate. Using CuCl/(±)-binap as the catalyst, the reaction was carried out in THF at rt. The leaving group of allyl phosphates was OP(O)(OsBu). The reaction among various kinds of terminal alkynes and allyl phosphates gave the corresponding products in more than 70% yields with more than 94% γ-E-selectivites. Alkynes bearing an EWG showed higher-selectivity than those bearing an ERG.⑵ Using the reaction among diphenylacetylene and allyl phosphate(Z)-2a as a template, We examined the reaction of copper-catalyzed γ-E-selective boryl-allylation among a symmetrical diaryl alkyne and an allyl phosphate. Using CuCl/(±)-binap as the catalyst, the reaction was carried out in toluene at 50 80 °C. The leaving group of allyl phosphates was OP(O)(OsBu). The reaction among various kinds of symmetrical diaryl alkynes and allyl phosphates gave the corresponding products in more than 50% yields with more than 90% γ-E-selectivites. The allyl phosphates bearing bulky ?-tert-butyl, ?-TMS, ?-phenyl, bulky ?-tert-butyl and ?-cyclohexyl also reacted smoothly with excellent selectivities. The diaryl alkynes, symmetrically substituted by EDG(para-methyl or para-methoxy) or EWG(para-fluro or para-trifluromethyl) groups, were reacted to give the products with isomeric purity >98%.⑶ We researched the reaction of copper-catalyzed γ-E-selective boryl-allylation among various kinds of aryl alkyl alkynes and allyl phosphates. Using CuCl/(±)-binap or CuCl/PPh3 as the catalyst, the reaction was carried out in DMF at 25 50 °C. The leaving group of allyl phosphates was OP(O)(OsBu)2 or phosphate group containing the 2-ethylhexyl moiety. The reaction gave the corresponding products in more than 50% yields with more than 90% γ-E-selectivites. Aryl with an EWG can improve the γ-selectivity. The stronger electronic absorption of group(such as CF3), the better selectivity. Also, as the growth of the carbon chain of alkyl, the selectivity get worse.⑷ We researched the reaction of copper-catalyzed γ-selective boryl-allylation among a symmetrical dialkyl alkyne(5-decyne) and various kinds of allyl phosphates. Using CuCl/PCy3 as the catalyst, the reaction was carried out in DMF or toluene at 50 65 °C. and gave the corresponding products in more than 30% yields. The primary allyl phosphates bearing the ?-substituents and ?,?-disubstitutents provided the products with 88?99% γ-isomeric purity.⑸ We researched the reaction of copper-catalyzed γ-selective boryl-allylation among diphenylacetylene and an allyl phosphate with a less bulky aryl(the aryl was phenyl or phenyl bearing an ERG on the para position). Using CuCl/PCy3 as the catalyst, the reaction was carried out in toluene at 50 °C, and gave the corresponding products in more than 69% yields with 99% γ-selectivites.⑹ We researched the reaction of copper-catalyzed α-selective boryl-allylation among various kinds of symmetrical diaryl alkynes and primary allyl phosphates. Using CuCl/(±)-binap or CuCl/PCy3 as the catalyst, the reaction among symmetrical diaryl alkynes and primary allyl phosphates was carried out in toluene at 50 65 °C, and gave the corresponding products in more than 60% yields with more than 80% α-selectivites. Increased the number of γ-substituent and β-substituent in primary allyl phosphates, α-selectivity of the reaction get better. The alkyne bearing an EWG on the phenyl ring gave greatly improved α-selectivites. The configuration of the C=C bond of allyl phosphates is reserved in the products.⑺ We researched the reaction of copper-catalyzed α-selective boryl-allylation among various kinds of aryl alkyl alkynes and primary allyl phosphates, Using CuCl/(±)-binap or CuCl/PPh3 or CuCl/PCy3 as the catalyst, the reaction among aryl alkyl alkynes and primary allyl phosphates was carried out in DMF at 50 °C, and gave the corresponding products in more than 50% yields with more than 80% α-selectivites. The alkynes bearing p-CF3 on the phenyl ring gave greatly improved α-selectivites.⑻ We researched the cross coupling of various kinds of 1,4-dienylboronates and aromatic or alkenyl halides. Using Pd(PPh3)4 or Pd(dba)2/Sphos as the catalyst, the reaction was carried out in dioxane at 60 100 °C, and formed the corresponding coupling products of polyenes and congjugated enynes in more than 70% yields.