Simon Woodward

Decoding the ‘black box’ reactivity that is organocuprate conjugate addition chemistry

Understanding of the 1,4-addition of organocuprates, especially LiCuR2 species, to enone Michael acceptors has blossomed in the light of recent kinetic, NMR, and theoretical investigations. These investigations have been reviewed and are compared to the various reaction co-ordinates they support. Emphasis is placed on relating the theoretical calculations to physical data extracted from real systems. The mechanism of cuprate conjugate addition is compared to related reactions including: additions to ynones, alkene carbocupration, and SN2′ allylic and propargylic substitution reactions.

Strong ligand accelerated catalysis by an Arduengo-type carbene in copper-catalysed conjugate addition

Abstract The addition of stabilised carbene ligand: CNMesCH 2 CH 2 N Mes (Mes=2,4,6-Me 3 C 6 H 2 ) results in a dramatic rate increase in the Cu(OTf) 2 -catalysed conjugate addition of ZnEt 2 to enones (OTf=triflate anion).

Rhodium‐Catalyzed Asymmetric 1,4‐Addition of Aryl Alanes to Trisubstituted Enones: Binap as an Effective Ligand in the Formation of Quaternary Stereocenters

All for one and 1,4-all: Readily available aryl alanes are used in the rhodium-catalyzed asymmetric conjugate addition reaction with a variety of cyclic and acyclic enones. The enhanced reactivity of the system allows the use of the common binap ligand for the generation of quaternary benzylic stereocenters in excellent enantioselectivity (see scheme).

Copper-catalysed asymmetric conjugate addition of organometallic reagents to linear enones using thiourethane ligands

Abstract In the presence of chiral thiourethane ligands [Cu(MeCN) 4 ]BF 4 forms active catalysts for the conjugate addition of MeMgBr, ZnEt 2 and AlR 3 (R = Me, Et) to non-3-en-2-one, hept-3-en-2-one, and 5-methylhex-3-en-2-one. Enantioselectivities of up to 51% are realised for these difficult substrates; for cyclohex-2-enone an e.e. of 42% is attained.

Copper-Catalysed Asymmetric Conjugate Addition of Organometallic Reagents to Linear Enones

Abstract Methods for enantioselective 1,4-addition of main-group organometallics to linear enones are overviewed. Thiourethane and thioether 1,1′-binaphthyl-based ligands are effective for copper-catalysed 1,4-addition of ZnEt2 and AlR3 (R=Me, Et) to trans-alkyl-3-en-2-ones; enantioselectivities of up to 72% e.e. are attained. In comparison 1,4-addition of ZnEt2 to 2-cyclohexenone proceeds in up to 77% e.e. with the same ligand family.

Practical dihydroxylation and C–C cleavage of unsaturated fatty acids

Abstract Unsaturated fatty acids [C 8 H 17 CH=CH(CH 2 ) n CO 2 H] ( n =7, 11) acids are cleanly dihydroxylated by hydrogen peroxide in the presence of catalytic amounts of H 2 WO 4 . Under molecular oxygen, in the presence of catalytic amounts of N -hydroxyphthalimide and Co(acac) 3 , the diols resulting from erucic ( n =11) and oleic ( n =7) acid undergo C–C cleavage.

Aerobic epoxidation via alkyl-2-oxocyclopentanecarboxylate co-oxidation with cobalt or manganese Jacobsen-type catalysts

Abstract In the presence of methyl, tert-butyl, or (−)-menthyl esters of 2-oxocyclopentanecarboxylic acids Jacobsen-type complexes of cobalt(II) and manganese(III) form active catalysts for alkene epoxidation using molecular oxygen. Alkyl-1-hydroxy-2-oxocyclopentanecarboxylates and 1-alkyl-2-oxo-hexanedicarboxylic acids are formed as co-oxidation products. The (−)-menthyl/cobalt system is selective for epoxide production but the products are racemic consistent with radical epoxidation in solution rather than at the cobalt complex. The manganese Jacobsen-type complex gives lower yields of epoxides (40–60%) but for 2,2-dimethylchromene and styrene these are optically active (12–60% ee).

On the use of mixtures of organotin species for catalytic enantioselective ketone allylation—a detective story

In the presence of enantiopure MTBH(2)(monothiobinaphthol, 2-hydroxy-2[prime or minute]mercapto-1,1[prime or minute]-binaphthyl; 0.2 eq.) quantitative allylation of ArC([double bond]O)Me takes place with impure Sn(CH(2)CH[double bond]CH(2))(4)(prepared from allyl chloride, air-oxidised magnesium and SnCl(4)) to yield tert-homoallylic alcohols in 85-92% ee. In the same process highly purified, or commercial, Sn(CH(2)CH[double bond]CH(2))(4) yields material of only 35-50% ee. The origin of these effects is the presence of small amounts of the compounds, EtSn(CH(2)CH[double bond]CH(2))(3), ClSn(CH(2)CH[double bond]CH(2))(3) ClSnEt(CH(2)CH[double bond]CH(2))(2) in the tetraallyltin sample and the presence of traces of water (which inhibits achiral background reactions). All the triallyl and diallyl species enhance the stereoselectivity in the catalytic allylation reaction, the chlorides more so than the ethyl compound. Hydrolysis of ClSnEt(CH(2)CH[double bond]CH(2))(2) affords crystallographically characterised Sn(4)(mu(3)-O)(mu(2)-Cl)(2)Cl(2)Et(4)(CH(2)CH[double bond]CH(2))(4). Reaction of this latter compound with MTBH(2) leads to the most potent catalyst.

Copper-catalysed asymmetric conjugate addition of organometallic reagents to enones using S,O-ligands with a xylofuranose backbone

Abstract The copper-catalysed enantioselective 1,4-addition reactions of diethylzinc to cyclohexenone and trimethylaluminium to E -non-3-en-2-one in the presence of thioether-alcohol ligands, which are easily prepared from d -(+)-xylose, resulted in e.e.s of up to 62% for cyclohexenone and 34% for E -non-3-en-2-one.

Copper-catalysed Asymmetric 1,4-addition of Organozinc Compounds to Linear Aliphatic Enones Using 2,2′-dihydroxy 3,3′-dithioether Derivatives of 1,1′-binaphthalene

Directed ortho dilithiation of bis(diethylcarbamate) or bis(MOM)-protected (Sa)-1,1′-bi(2-naphthol) followed by treatment with R2S2 [R = Me, Ph (X-ray structure)] or Me2Se2 cleanly affords the 3,3′ derivatives; the free naphthols are produced on deprotection. In the case of the bis(MOM) series, but not that of the bis(carbamates), some racemisation occurs. The ligand 2,2′-dihydroxy-3,3′-dimethylthio-1,1′-binaphthalene shows optimal performance in the addition of ZnEt2 to linear aliphatic enones (E)-R1C(O)CH=CHR2. Variation of the steric demands of R1 and R2 generates catalytic results consistent with binding of a zinc-based Lewis acid anti to the ene function and with the reactive conformation being s-cis. With enones containing the functions R2 = (CH2)nCH(OAlkyl)2 (n = 0−2), the ZnEt2 addition products undergo base-promoted cyclisation.