The Synthetic Routes of rel-(2R,4aR,8aS)-Hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one

The synthesis of complex organic molecules is a challenging task in the chemical industry.
One such molecule is rel-(2R,4aR,8aS)-Hexahydro-1,1,5,5-tetramethyl-2H-2,4a-methanonaphthalen-8(5H)-one, also known as the "Boehringer Ingelheim molecule".
This molecule is a key component in the development of a new class of therapeutic agents for the treatment of tuberculosis.

The synthesis of the Boehringer Ingelheim molecule involves several complex steps and requires a high level of expertise and specialized equipment.
There are several synthetic routes available for the synthesis of this molecule, each with its own advantages and disadvantages.
In this article, we shall discuss three of the most widely used synthetic routes for the synthesis of the Boehringer Ingelheim molecule.

Route 1: via the Grignard Reaction

The Grignard reaction is a common synthetic method in organic chemistry.
It involves the reaction of an alkylhalide with magnesium metal to form a Grignard reagent.
The Grignard reagent can then be used as a nucleophile in a variety of reactions.

To synthesize the Boehringer Ingelheim molecule via the Grignard reaction, one starts with the synthesis of the Grignard reagent.
A suitable alkyl halide, such as 2-bromo-1-butanol, is treated with magnesium metal to form the Grignard reagent.
This reagent is then used in a reaction with a protected aromatic amine, such as 2-chloro-1-[2-(4-methoxyphenyl)ethyl]-4,5-dihydroimidazo[1,2-d][1,4]benzoxepin-9-one, to form the desired product.

Advantages of this route include the ease of preparation and handling of the Grignard reagent, as well as the low cost of the starting materials.
However, the Grignard reaction can be sensitive to air and moisture, and requires careful handling to prevent unwanted side reactions.

Route 2: via the Suzuki Reaction

The Suzuki reaction is a widely used method for the coupling of boronic acids and aryl halides.
In this reaction, a boronic acid and an aryl halide are treated with a palladium catalyst in the presence of a base to form a new carbon-carbon bond.

To synthesize the Boehringer Ingelheim molecule via the Suzuki reaction, one starts with the synthesis of the boronic acid.
Boron trifluoride diisopropanol is treated with a suitable boron source, such as boric acid, to form the boronic acid.
This boronic acid is then used in a reaction with an aryl halide, such as 2-iodo-6-nitro-benzene, and a palladium catalyst, such as tetrakis(triphenylphosphine)palladium(0), to form the desired product.

Advantages of this route include the high yield and selectivity of the reaction, as well as the mild conditions used for the reaction.
However, the Suzuki reaction requires specialized equipment and the use of expensive catalysts, which can increase the cost of the synthesis.

Route 3: via the Stille Reaction

The Stille reaction is a method for the coupling of aryl halides and boronic acids.
In this reaction, a boronic acid and an aryl halide are treated with a copper catalyst in the presence of a base to form a new carbon-carbon bond.

To synthesize the Boehringer Ingelheim molecule via the Stille reaction, one starts with the synthesis of the boronic acid.
Boron trifluoride diisopropanol is treated with a suitable boron source, such as boric acid, to form the boronic acid.
This boronic acid is then used in a reaction with an