Tertiary Alkyl Bromides Research Articles

ChemInform Abstract: Copper‐Catalyzed Cross‐Coupling Reaction of Allyl Boron Ester with 1°/2°/3°‐Halogenated Alkanes.

AbstractThe scalable method succeeds efficiently starting from primary, secondary, and tertiary alkyl bromides and tolerates various functional groups.

ChemInform Abstract: Ni‐Catalyzed Reductive Coupling of Alkyl Acids with Unactivated Tertiary Alkyl and Glycosyl Halides.

AbstractThis reaction works with sterically hindered unactivated tertiary alkyl bromides, as well as with primary and secondary alkyl halides and glycosyl bromides.

Computational Insight into Nickel-Catalyzed Carbon-Carbon versus Carbon-Boron Coupling Reactions of Primary, Secondary, and Tertiary Alkyl Bromides.

The nickel-catalyzed alkyl-alkyl cross-coupling (C-C bond formation) and borylation (C-B bond formation) of unactivated alkyl halides reported in the literature show completely opposite reactivity orders in the reactions of primary, secondary, and tertiary alkyl bromides. The proposed Ni(I) /Ni(III) catalytic cycles for these two types of bond-formation reactions were studied computationally by means of DFT calculations at the B3LYP level. These calculations indicate that the rate-determining step for alkyl-alkyl cross-coupling is the reductive elimination step, whereas for borylation the rate is determined mainly by the atom-transfer step. In borylation reactions, the boryl ligand involved has an empty p orbital, which strongly facilitates the reductive elimination step. The inability of unactivated tertiary alkyl halides to undergo alkyl-alkyl cross-coupling is mainly due to the moderately high reductive elimination barrier.

Ni-catalyzed reductive coupling of alkyl acids with unactivated tertiary alkyl and glycosyl halides.

This work highlights Ni-catalyzed reductive coupling of alkyl acids with alkyl halides, particularly sterically hindered unactivated tertiary alkyl bromides for the production of all carbon quaternary ketones. The reductive strategy is applicable to α-selective synthesis of saturated, fully oxygenated C-acyl glycosides through easy manipulations of the readily available sugar bromides and alkyl acids, avoiding otherwise difficult multistep conversions. Initial mechanistic studies suggest that a radical chain mechanism (cycle B, Scheme 1) may be plausible, wherein MgCl2 promotes the reduction of Ni(II) complexes.

ChemInform Abstract: Nickel‐Catalyzed Dimerization of Pyrrolidinoindoline Scaffolds: Systematic Access to Chimonanthines, Folicanthines and (+)‐WIN 64821.

AbstractAn alternative catalytic protocol for the dimerization of tertiary alkyl bromides using manganese as reductant is developed and applied to the total synthesis of dimeric alkaloids such as chimonanthine (V), folicanthine (VI) and the potent substance P antagonist (+)‐WIN 64821 (IX) is also reported.

High- versus low-quality graphene: a mechanistic investigation of electrografted diazonium-based films for growth of polymer brushes.

Electrografting using aryldiazonium salts provides a fast and efficient technique to functionalize commercially available 3-5 layered graphene (vapour-deposited) on nickel. In this study, Raman spectroscopy is used to quantify the grafting efficiency of cyclic voltammetry which is one of the most versatile, yet simple, electrochemical techniques available. To a large extent the number of defects/substituents introduced to the basal plane of high-quality graphene by this procedure can be controlled through the sweeping conditions employed. After extended electrografting the defect density reaches a saturation level ( ∼ 10(13) cm(-2)) which is independent of the quality of the graphene expressed through its initial content of defects. However, it is reached within fewer voltammetric cycles for low-quality graphene. Based on these results it is suggested that the grafting occurs (a) directly at defect sites for, in particular, low-quality graphene, (b) directly at the basal plane for, in particular, high-quality graphene, and/or (c) at already grafted molecules to give a mushroom-like film growth for all films. Moreover, it is shown that a tertiary alkyl bromide can be introduced at a given surface density to serve as radical initiator for surface-initiated atom transfer radical polymerization (SI-ATRP). Brushes of poly(methyl methacrylate) are grown from these substrates, and the relationship between polymer thickness and sweeping conditions is studied.

Ni-Catalyzed Reductive Homocoupling of Unactivated Alkyl Bromides at Room Temperature and Its Synthetic Application

A room-temperature Ni-catalyzed reductive approach to homocoupling of unactivated primary, secondary, and tertiary alkyl bromides is described. The catalytic system can be easily generated from air-stable and cheap materials and demonstrates broad functional group tolerance, thus allowing facile access to useful dimeric triterpene and lignan-like molecules. Moreover, the dimerization of tertiary bromide 6 efficiently establishes sterically hindered vicinal quaternary carbons (C3a and C3a'), which is a key linkage of intriguing bispyrrolo[2,3-b]indoline alkaloids, thereby enabling us to complete the total syntheses of racemic chimonanthine (9) and folicanthine (10). In addition, this dimerization method can be expanded to the highly stereoselective synthesis of bisperhydrofuro[2,3-b]furan (5a) and the dimeric spiroketal 5b, signifying the involvement of possible radical species.

Palladium-Catalyzed C–H Activation/Cross-Coupling of Pyridine N-Oxides with Nonactivated Secondary Alkyl Bromides

An unexpected C-H activation/C-C cross-coupling reaction has been found to occur between pyridine N-oxides and general nonactivated secondary and even tertiary alkyl bromides. It provides a practically useful approach for the synthesis of alkylated pyridine derivatives. Experimental observations indicated that the C-Br cleavage step involves a radical-type process. Thus, the title reaction provides a rather extraordinary example of Pd-catalyzed cross-coupling of secondary and tertiary aliphatic electrophiles.

Nickel-Catalyzed Coupling Reactions of Alkyl Electrophiles, Including Unactivated Tertiary Halides, To Generate Carbon–Boron Bonds

Through the use of a catalyst formed in situ from NiBr(2)·diglyme and a pybox ligand (both of which are commercially available), we have achieved our first examples of coupling reactions of unactivated tertiary alkyl electrophiles, as well as our first success with nickel-catalyzed couplings that generate bonds other than C-C bonds. Specifically, we have determined that this catalyst accomplishes Miyaura-type borylations of unactivated tertiary, secondary, and primary alkyl halides with diboron reagents to furnish alkylboronates, a family of compounds with substantial (and expanding) utility, under mild conditions; indeed, the umpolung borylation of a tertiary alkyl bromide can be achieved at a temperature as low as -10 °C. The method exhibits good functional-group compatibility and is regiospecific, both of which can be issues with traditional approaches to the synthesis of alkylboronates. In contrast to seemingly related nickel-catalyzed C-C bond-forming processes, tertiary halides are more reactive than secondary or primary halides in this nickel-catalyzed C-B bond-forming reaction; this divergence is particularly noteworthy in view of the likelihood that both transformations follow an inner-sphere electron-transfer pathway for oxidative addition.

Nickel‐Catalyzed Heck‐Type Alkenylation of Secondary and Tertiary α‐Carbonyl Alkyl Bromides

Ni made it! A novel Heck-type reaction of secondary and tertiary α-carbonyl alkyl bromides, most likely involving a radical process, was achieved through the use of a nickel catalyst. Various substituted styrenes and 1,1-diaryl alkenes were utilized as substrates to easily construct α-alkenyl carbonyl compounds with tertiary or quaternary carbon centers. A catalytic cycle involving NiI/NiII is proposed based on our experimental results. EWG=electron-withdrawing group. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The Study of Substitution and Elimination Reactions Using Gas Chromatography: An Examination of the Effects of Alkane and Base Structure on Product Distributions

An experiment that compares product distribution obtained by either substitution or elimination utilizing alkyl bromides and methoxide, ethoxide, or t-butoxide as the base (or nucleophile) is described. The change in product distribution caused by steric effects of the base and substrate are readily apparent. Prior work on this experiment focused on only the olefin products using a method without internal standards. The experiment examines all ether and olefin products as well as starting material and illustrates key principles of SN2–SN1 and E2–E1 reactions. For this experiment, a gas chromatographic method was developed that allows for complete product analysis. The new method examines the product distributions as a function of primary, secondary, and tertiary alkylbromide and base structure and can be expanded to include the interpretation of gas chromatographic data. Relative response factors were developed for the ether versus olefin products. If desired, the data in the supporting information can be utilized for in-class problems pertaining to substitution and elimination reactions.

Development of a Practical and Efficient Synthesis of Chloromethyl 2-Ethoxy-2-methylpropanoate

An efficient synthesis of chloromethyl 2-ethoxy-2-methylpropanoate from 2-bromoisobutyric acid is reported. Four developments were key to this route: (i) a mild, base-mediated ethanolysis of a tertiary alkyl bromide, (ii) a sodium bisulfite purge of 2-methylacrylic acid, (iii) preparation of a thiomethyl ester via a formal Pummerer process with DMSO, and (iv) improved conversion of a thiomethyl ester to a chloromethyl ester through suppression of a competing chlorination pathway.

ChemInform Abstract: Silver‐Catalyzed Benzylation and Allylation of Tertiary Alkyl Bromides with Organozinc Reagents.

AbstractSilver salts catalyze the benzylation and allylation of tertiary alkyl bromides with organozinc reagents.

Silver‐Catalyzed Benzylation and Allylation of Tertiary Alkyl Bromides with Organozinc Reagents

Silver salts catalyze the benzylation and allylation of tertiary alkyl bromides with organozinc reagents. The reactions create quaternary carbon centers efficiently. Treatment of gem-dibromoalkanes with benzylic or allylic zinc reagents under silver catalysis leads to dibenzylation or diallylation. The functional-group compatibility of the present reactions is wider than that of the previous reactions with Grignard reagents.

Copper-Catalyzed Allylation of Alkyl Halides with Allylic Grignard Reagents

Abstract Treatment of alkyl halides, including secondary and tertiary alkyl bromides, with allylic Grignard reagents in the presence of a catalytic amount of copper(II) triflate in diisopropyl ether at 25 °C yielded the corresponding allylated products in high yields. The coupling reactions of tertiary alkyl halides lead to construction of allylated quaternary carbon centers. The active species is likely to be allylcuprate.

Silver-catalyzed cross-coupling reactions of alkyl bromides with alkyl or aryl Grignard reagents

Treatment of secondary or tertiary alkyl bromides with alkyl Grignard reagents in the presence of catalytic amounts of silver bromide and potassium fluoride in CH 2Cl 2 afforded the corresponding cross-coupling products in reasonable yields. Moreover, silver showed catalytic activity for the cross-coupling reactions of alkyl bromides with aryl Grignard reagents.

Copper-Catalyzed Reaction of Alkyl Halides with Cyclopentadienylmagnesium Reagent

Treatment of alkyl halides, including tertiary alkyl bromides, with cyclopentadienylmagnesium bromide in the presence of a catalytic amount of copper(II) triflate yielded the corresponding cyclopentadienylated products in high yields. The following hydrogenation of the products provided alkyl-substituted cyclopentanes.

Silver-Catalyzed Benzylation and Allylation Reactions of Tertiary and Secondary Alkyl Halides with Grignard Reagents

Treatment of alkyl halides, including tertiary alkyl bromides, with benzylic or allylic Grignard reagent in the presence of a catalytic amount of silver nitrate in ether yielded the corresponding cross-coupling products in high yields. The coupling reactions of tertiary alkyl halides provide efficient access to quaternary carbon centers.

A Direct Functionalization of Tertiary Alkyl Bromides with O‐, N‐, and C‐Nucleophiles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A direct functionalization of tertiary alkyl bromides with O-, N-, and C-nucleophiles

Silver oxide used in stoichiometric amounts promoted the direct functionalization of tert-alkyl bromides and provided the desired adducts in 39–96% isolated yield. Reaction of tert-bromides with carboxylic acids yielded esters, with alcohols and phenols yielded alkyl and aryl ethers, with amines and anilines yielded selectively mono-alkylated amines and anilines, and with a C-nucleophile yielded an all-carbon quaternary hydrocarbon. The method was applied to a sequential alkylation of a primary amine with two different alkyl bromides yielding selectively a tertiary amine with three different substituents in one-pot.