Related Experiment Video
Updated: Jul 5, 2026
07:50
Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Chemoselective functionalization of 3,3'-substituted BINOL derivatives
Carmine Coluccini1, Antonio Castelluccio, Dario Pasini
1Department of Organic Chemistry, University of Pavia, Viale Taramelli 10, Pavia, Italy.
The Journal of Organic Chemistry
|April 30, 2008
Summary
Chemoselective protection of binaphthyl alcohols was achieved using TBS protection on less hindered positions. This strategy allows for orthogonal manipulation of functional groups using BOC protecting groups in high yields.
Area of Science:
- Organic Chemistry
- Stereoselective Synthesis
- Protecting Group Chemistry
Background:
- Optically active binaphthyl skeletons are valuable chiral scaffolds in asymmetric synthesis.
- Selective functionalization of vicinal alcohols on these skeletons presents a synthetic challenge.
- Orthogonal protecting group strategies are crucial for complex molecule synthesis.
Purpose of the Study:
- To develop an efficient chemoselective method for differentiating vicinal phenolic and benzylic alcohols on binaphthyl systems.
- To enable subsequent orthogonal functionalization at specific positions of the binaphthyl scaffold.
Main Methods:
- Utilized tert-butyldimethylsilyl (TBS) protection for selective blocking of less sterically hindered, external 3,3' benzylic alcohol positions.
- Employed tert-butoxycarbonyl (BOC) protecting groups for orthogonal manipulation of functionalities at the 2,2' or 3,3' positions.
Main Results:
- Achieved efficient chemoselective differentiation of vicinal alcohols on optically active binaphthyl skeletons.
- Demonstrated high yields in subsequent functional group manipulations facilitated by orthogonal TBS and BOC protection.
Conclusions:
- The developed TBS protection strategy provides a facile route for selective alcohol differentiation on binaphthyl scaffolds.
- The orthogonal nature of TBS and BOC protecting groups allows for versatile and high-yielding synthetic transformations.
Related Concept Videos
02:36Regioselectivity and Stereochemistry of Hydroboration
A significant aspect of hydroboration–oxidation is the regio- and stereochemical outcome of the reaction.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
01:11Nucleophilic Aromatic Substitution: Elimination–Addition
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic...
01:38Preparation of Alcohols via Substitution Reactions
Overview
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...
03:08Hydroboration-Oxidation of Alkenes
In addition to the oxymercuration–demercuration method, which converts the alkenes to alcohols with Markovnikov orientation, a complementary hydroboration-oxidation method yields the anti-Markovnikov product. The hydroboration reaction, discovered in 1959 by H.C. Brown, involves the addition of a B–H bond of borane to an alkene giving an organoborane intermediate. The oxidation of this intermediate with basic hydrogen peroxide forms an alcohol.
01:25Radical Anti-Markovnikov Addition to Alkenes: Overview
The addition of hydrogen bromide to alkenes in the presence of hydroperoxides or peroxides proceeds via an anti-Markovnikov pathway and yields alkyl bromides.