Notable reactions NiCl/CrCl2-catalyzed coupling reaction between vinyl iodides and aldehydes( nhk coupling). a Pd(0)catalyzed and thallium hydroxide assisted synthesis of cis-trans conjugated dienes from vinyl iodides and vinyl boronic acids a New methods for the construction of N-acyl vinylogous ureas
Notable Reactions Notable Reactions NiCl 2/CrCl 2 -catalyzed coupling reaction between catalyzed coupling reaction between vinyl iodides and aldehydes (NHK Coupling). vinyl iodides and aldehydes (NHK Coupling). Pd(0) catalyzed and thallium hydroxide assisted Pd(0) catalyzed and thallium hydroxide assisted synthesis of synthesis of cis -trans conjugated dienes from vinyl conjugated dienes from vinyl iodides and vinyl boronic acids. iodides and vinyl boronic acids. New Methods for the construction of N New Methods for the construction of N -acyl vinylogous ureas vinylogous ureas
NiCl/CrCl2 Coupling CrCl. DME OH 25°C R R X=L. Br Le CrCl2, DMF Me OH This carbon-carbon bond forming reaction is highly chemoselective Aldehyde carbonyls are selectively attacked even in the presence of other electrophilic groups e.g. Ketones, esters, and nitriles Gives benzylic or allylic alcohols Takai, K; Kimura, K; Kuroda, T; Hiyama, T, Nozaki, H. Tetrahedron Lett. 1983, 24, 5281
NiCl2/CrCl2 Coupling Coupling 1 R X + H R' O CrCl2, DMF 25°C R R' OH X=I, Br i.e.1 I Me + H O O CrCl2, DMF 25°C Me OH O •This carbon This carbon-carbon bond forming reaction is carbon bond forming reaction is highly chemoselective highly chemoselective • Aldehyde carbonyls Aldehyde carbonyls are selectively selectively attacked attacked even in the presence even in the presence of other electrophilic groups of other electrophilic groups e.g. Ketones, esters, and nitriles e.g. Ketones, esters, and nitriles •Gives benzylic benzylic or allylic allylic alcohols alcohols 1Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1983, 24, 5281
NiCl2/CrCl Coupling Cont Problem: Reaction didnt always work. The success of the Cr(ll) coupling depended on the batch of the Crc .Possible reasons: Quality of CrCl? NO! Homemade crcl, reagent didnt help .Possible contaminant in the CrCl? YYes! Kishi examined the effect of transition metals on the reaction and found that niCh had an effect
NiCl2/CrCl2 Coupling Cont. Coupling Cont. • Problem: Problem: Reaction didn’t always work. The success Reaction didn’t always work. The success of the Cr(II) coupling depended on the batch of the of the Cr(II) coupling depended on the batch of the CrCl2. •Possible Reasons: Possible Reasons: • Quality of CrCl Quality of CrCl2? NO! Homemade CrCl Homemade CrCl2 reagent didn’t help reagent didn’t help •Possible contaminant in the CrCl Possible contaminant in the CrCl2? Yes!! Kishi examined the effect of transition metals Kishi examined the effect of transition metals on the reaction and found that on the reaction and found that NiCl2 had an effect. had an effect
NiCl2/CrCl Coupling Cont The stereochemistry of the trans or cis iodo olefin is retained Reaction produces diastereomers although a preference for one is usually observed. Has an advantage over conventional carbonyl additions NiCk=Catalytic amount CrCl=Excess Kishi et al. J. Am. Chem. Soc. 1986. 108. 5644
NiCl2/CrCl2 Coupling Cont. Coupling Cont. • The stereochemistry of the The stereochemistry of the trans or cis iodo olefin is retained. olefin is retained. • Reaction produces Reaction produces diastereomers diastereomers although a although a preference for one is usually observed. preference for one is usually observed. • Has an advantage over conventional carbonyl Has an advantage over conventional carbonyl additions. additions. NiCl2 = Catalytic amount = Catalytic amount CrCl2 = Excess = Excess Kishi et al. J. Am. Chem. Soc. 1986, 108, 5644
NiCl/CrCl2 Coupling Cont Transmetalation Cr(lr) Ni-Ⅹ Cr(Il) XEL Br. oti Oxidative Addition RCHO Ni(0) Ni(n)* R 2Cr(Im) OH Takai, K, Tagashira, M, Kuroda, T, Oshima, K; Utimoto, K; Nozaki, H J. Am. Chem. Soc. 1986, 108, 6048
NiCl2/CrCl2 Coupling Cont. Coupling Cont. Transmetalati Transmetalation X Ni-X Cr(III) RCHO R OH Cr(III) Ni(0) Ni(II) 2Cr(III) 2Cr(II) X= I, Br, OTf Oxidative Addition Oxidative Addition Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048