56745-70-1

Upstream product

• 693-03-8 n-butyl magnesium bromide 
• 75-77-4 chloro-trimethyl-silane 
• 930-68-7 cyclohexenone 
• 109-72-8 n-butyllithium 
• 546-68-9 titanium(IV)isopropoxide 
• 16029-98-4 trimethylsilyl iodide 
• 34948-25-9 n-butylcopper 
• 693-04-9 butyl magnesium bromide 

Downstream Products

• 39178-69-3 rac-3-butylcyclohexanone 

Relevant academic research and scientific papers

Intramolecular C-H insertion reactions of (η5-Cyclopentadienyl)dicarbonyliron carbene complexes: Scope of the reactions and application to the synthesis of (±)-sterpurene and (±)-pentalenene

(η5-Cyclopentadienyl)dicarbonyliron carbene complexes, [(η5C5H5) (CO)2Fe=CHR]+BF4-, are generated as reactive intermediates from thioether derivatives, (η5-C5H5)(CO)2FeCH(R)SPh, by S-alkylation with trimethyloxonium tetrafluoroborate and loss of thioanisole. The carbene complexes undergo intramolecular C-H insertion into appropriately situated side chains to form cyclopentane derivatives. The reaction has been developed into a general procedure employing cycloalkanones as scaffolds bearing the iron carbene moieties and the side chains at C(2) and C(3), respectively. The products of the intramolecular insertion reactions are substituted bicyclo[n.3.0]alkanones. The scope and limitations of the reaction are described. The reaction is applied to a total synthesis of sterpurene and to a formal synthesis of pentalenene. Overall, this approach to cyclopentane annulation complements the related metal-catalyzed insertion reactions of diazocarbonyl compounds, which are also believed to occur via metal carbene complexes.

Isotope effects and the mechanism of chlorotrimethylsilane-mediated addition of cuprates to enones

Kinetic isotope effects were determined for the chlorotrimethylsilane- mediated reactions of cyclohexenone with lithium dibutylcuprate in tetrahydrofuran and with lithium butyl(tert-butylethynyl)cuprate in ether. For the reaction in tetrahydrofuran, the observation of a significant carbonyl oxygen isotope effect (16k/17k = 1.018-1.019) and small olefinic carbon isotope effects (12k/13k = 1.003-1.008) is consistent with rate- limiting silylation of an intermediate π-complex. Theoretically predicted isotope effects for model reactions support this conclusion. Rate-limiting silylation is also supported by relative reactivity studies of chlorotrimethylsilane versus chlorodimethylphenylsilane. The absence of a significant butyl-group carbon isotope effect on product formation indicates that the cuprate butyl groups are nonequivalent in the intermediate leading to the product-determining step. In diethyl ether the isotope effects revert to values similar to those found previously in reactions of cyclohexenone with lithium dibutylcuprate in the absence of chlorotrimethylsilane, consistent with no change in the overall mechanism in this solvent. A mechanistic hypothesis for the differing effects of TMSCl with changes in solvent and substrate is presented.

New copper chemistry, part 29: Re-evaluation of organocuprate reactivity: Logarithmic reactivity profiles for iodo- versus cyano-Gilman reagents in the reactions of organocuprates with 2-cyclohexenone and iodocyclohexane

Iodo-Gilman reagents Me2-CuLi·LiI, Bu2CuLi·LiI, and BuThCu-Li·LiI and cyano-Gilman reagents (nee "higher order cyanocuprates" Me2Cu-Li·LiCN, Bu2CuLi·LiCN, and BuTh-CuLi·LiCN react with 2-cyclohexenone at various rates, which depend upon the R groups (Me, Bu, Th=thienyl), Li salt (LiI vs. LiCN), solvent (ether vs. THF), and amount of trimethylsilyl chloride (TMSCl) additive. The effect of the Li salt (CuI vs. CuCN precursor) is less than that of solvent or TMSCl. The butylcuprate-iodocyclohexane reaction has also been examined as a function of Li salt, solvent, and TMSCl additive, and similar effects are observed. The reactivity matrix R with elements ri,j is a convenient way to store and present a large amount of relative reactivity data. Entry ri,j is the ratio of the rate with reagent i to the rate with reagent j, which we approximate by using yields measured after a short time (4 s). The logarithmic reactivity profile (LRP) provides an efficient means for determining yields under conditions where such comparisons are valid. The results of a large number of 4-point LRPs and related reactions are tabulated and analyzed to provide a clearer picture of organocuprate reactivity.

The Kharasch reaction revisited: CuX3Li2-catalyzed conjugate addition reactions of Grignard reagents

The conjugate addition of Grignard reagents RMgX to α,β-unsaturated ketones and esters is effectively catalyzed by soluble copper ate-complexes of the type CuX3Li2, e.g.CuI*2LiCl.In the presence of Me3SiCl the corresponding ketone enolsilanes are formed in high yield and selectivity.Diastereoselectivity in the case of chiral ketones is similar to that observed by using stoichiometric amounts of cuprates R2CuLi.Thus CuX3Li2-catalyzed 1,4-additions of Grignard reagents may be an industrially viable process.Keywords: Copper; Magnesium; Lithium; Silicon; Ketone; Enolsilanes

Iodotrimethylsilane-Promoted Additions of Monoorganocopper Compounds to α,β-Unsaturated Ketones, Esters, and Lactones

Conjugate additions with the efficient monoorganocopper-iodotrimethylsilane combination, exemplified mainly with methylcopper, butylcopper, and tert-butylcopper, proceed cleanly, smoothly, and rapidly to a variety of α,β-unsaturated carbonyl compounds; cy

Copper-catalyzed reactions of organotitanium reagents. Highly selective SN2′-allylation and conjugate addition

In the presence of a catalytic amount of CuI·ILiCl, alkyltitanium (RTi(O-I-Pr)3) and titanate reagents (RnTi(O-i-Pr)5-nLi) undergo highly selective SN2′-alkylation reactions with allylic chlorides and allylic diethylphosphates in high yields. The regioselectivity of the reaction is as high as 99.8%. The reaction proceeds with excellent anti-stereoselectivity with respect to the nucleophile and the leaving group, and exhibits high 1,2-anti-diastereoselectivity with a δ-chiral allylic chloride. The catalytic copper reagent is also a mild agent to transfer an alkyl group to an enone in the presence of Me3SiCl. The alkyltitanium-based catalytic reagent selectively reacts with an allylic phosphate rather than with an enone, while in the presence of a silicon activator, it reacts preferentially with the enone rather than with the phosphate. 1H NMR studies on a mixture of Me2CuLi and TiCl(O-i-Pr)3 provided information on reagent composition.

Copper-Catalyzed Reactions of Organotitanium Reagents. Highly SN2'- and Anti-Selective and Diastereo- and Chemoselective Alkylation of Allylic Chlorides and Phosphates

Organotitanium reagents undergo Cu(I)-catalyzed SN2' substitution reactions with allylic chlorides and phosphates in a regio-, stereo-, and chemoselective manner: in the presence of Me3SiCl or Me3SiOSO2CF3, they undergo preferential conjugate addition to enones.

An alternative procedure for the O-trimethylsilylation of enolates generated by copper-catalyzed 1,4-additions

Anhydrous lithium bromide has been successfully used as an additive instead of hexamethylphosphoric triamide in the O-trimethylsilation of enolates generated by copper halide-catalyzed reaction of Grignard reagents with a number of α,β-unsaturated carbony