Abstract:The cinchona alkaloid dimer (DHQD) PHAL has been shown to be a broadly applicable catalyst for asymmetric halogenations. However, this catalyst does not have to be dimeric and a class of monomeric quinidine and quinine-derived catalysts was prepared, often showing superior selectivity in bromolactonisations of terminal alkynoic acids. Mechanistic investigations show that these organocatalysts act as host molecules that can bind carboxylic acid-based substrates as guests with substantial binding constants. Base… Show more
“…Such transition state models predicted facilitation of the nucleophilic attack by the carboxylate anion to one side of the alkene moiety of the meso -substrate in the five-membered lactone system to yield the (3 S , 5 R )-product preferentially. These computational results prompted us to design the catalytic asymmetric iodolactonization of prochiral diallyl acetic acids as shown in Figure 5 (Ikeuchi et al., 2012, Jiang et al., 2018, Klosowski and Martin, 2018, Knowe et al., 2018, Murai et al., 2014a, Murai et al., 2014b, Wilking et al., 2013, Wilking et al., 2016). Figure 5Catalytic Asymmetric Five-Membered Iodolactonization Using Zn 3 (OAc) 4 -3,3′-bis(aminoimino)binaphthoxide ( tri-Zn ) Catalyst…”
SummaryCooperative activation using halogen bonding and hydrogen bonding works in metal-catalyzed asymmetric halolactonization. The Zn3(OAc)4-3,3′-bis(aminoimino)binaphthoxide (tri-Zn) complex catalyzes both asymmetric iodolactonization and bromolactonization. Carboxylic acid substrates are converted to zinc carboxylates on the tri-Zn complex, and the N-halosuccinimide (N-bromosuccinimide [NBS] or N-iodosuccinimide [NIS]) is activated by hydrogen bonding with the diamine unit of chiral ligand. Halolactonization is significantly enhanced by the addition of catalytic I2. Density functional theory calculations revealed that a catalytic amount of I2 mediates the alkene portion of the substrates and NIS to realize highly enantioselective iodolactonization. The tri-Zn catalyst activates both sides of the carboxylic acid and alkene moiety, so that asymmetric five-membered iodolactonization of prochiral diallyl acetic acids proceeded to afford the chiral γ-butyrolactones. In the total description of the catalytic cycle, iodolactonization using the NIS-I2 complex proceeds with the regeneration of I2, which enables the catalytic use of I2. The actual iodination reagent is I2 and not NIS.
“…Such transition state models predicted facilitation of the nucleophilic attack by the carboxylate anion to one side of the alkene moiety of the meso -substrate in the five-membered lactone system to yield the (3 S , 5 R )-product preferentially. These computational results prompted us to design the catalytic asymmetric iodolactonization of prochiral diallyl acetic acids as shown in Figure 5 (Ikeuchi et al., 2012, Jiang et al., 2018, Klosowski and Martin, 2018, Knowe et al., 2018, Murai et al., 2014a, Murai et al., 2014b, Wilking et al., 2013, Wilking et al., 2016). Figure 5Catalytic Asymmetric Five-Membered Iodolactonization Using Zn 3 (OAc) 4 -3,3′-bis(aminoimino)binaphthoxide ( tri-Zn ) Catalyst…”
SummaryCooperative activation using halogen bonding and hydrogen bonding works in metal-catalyzed asymmetric halolactonization. The Zn3(OAc)4-3,3′-bis(aminoimino)binaphthoxide (tri-Zn) complex catalyzes both asymmetric iodolactonization and bromolactonization. Carboxylic acid substrates are converted to zinc carboxylates on the tri-Zn complex, and the N-halosuccinimide (N-bromosuccinimide [NBS] or N-iodosuccinimide [NIS]) is activated by hydrogen bonding with the diamine unit of chiral ligand. Halolactonization is significantly enhanced by the addition of catalytic I2. Density functional theory calculations revealed that a catalytic amount of I2 mediates the alkene portion of the substrates and NIS to realize highly enantioselective iodolactonization. The tri-Zn catalyst activates both sides of the carboxylic acid and alkene moiety, so that asymmetric five-membered iodolactonization of prochiral diallyl acetic acids proceeded to afford the chiral γ-butyrolactones. In the total description of the catalytic cycle, iodolactonization using the NIS-I2 complex proceeds with the regeneration of I2, which enables the catalytic use of I2. The actual iodination reagent is I2 and not NIS.
“…[25][26][27][28][29][30][31][32][33][34] Following these reports, enantioselective bromolactonization reactions of alkynes were developed by some of the authors of this work. 35,36 Although numerous chiral catalysts have been developed for the enantioselective halolactonization reaction, their mode of action oen remains elusive. Only very recently, the mechanistic aspects of the (DHQD) 2 PHAL catalysed asymmetric chlorolactonization reaction were unveiled by a joint effort by Jackson and Borhan.…”
Ab initio dynamics of the halolactonization reaction provide insights into the diastereoselectivity of the reaction. Noncovalent interactions between the substrate, halogen source and solvent are revealed to direct the formation of the syn-product.
“…Enantioselective dichlorinations of alkenes without directing hydroxyl or amide groups were disclosed by Hennecke and co‐workers in 2019 (Scheme 18). [51] This required the use of unsymmetrical chinchona alkaloid based organocatalyst 91 , carrying a sterically demanding secondary alcohol at the phthalazine moiety [52] . Similar to the example reported by Borhan and co‐workers, separate electrophilic (DCDMH) and nucleophilic halogen sources (triethylchlorosilane (TES‐Cl)) were used, but carrying out the reaction in nonpolar solvents enabled the use of stoichiometric amounts of halide.…”
Section: Dichlorination Dibromination and Mixed Dihalogenationsmentioning
The dihalogenation of alkenes is one of the classic reactions in organic chemistry and a prime example of an electrophilic addition reaction. The often observed anti‐selectivity in this addition reaction can be explained by the formation of a haliranium‐ion intermediate. Although dihalogenations have been studied for more than a century, the development of reagent‐controlled, enantioselective dihalogenation has proved to be very difficult. Only recently, significant progress has been achieved. In this review, an overview on current method development in enantioselective dihalogenation is provided and mechanistic aspects that render this transformation challenging are discussed.
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