Dötz reaction
Encyclopedia
The Wulff-Dötz reaction is the chemical reaction
of an aromatic or vinylic alkoxy pentacarbonyl chromium
carbene complex
with an alkyne
and carbon monoxide
to give a Cr(CO)3-coordinated substituted phenol
. Several reviews have been published. It is named after the German chemist Karl Heinz Dötz (b. 1943) and the American chemist William D. Wulff (b. 1949) at Michigan State University. The reaction was first discovered by Karl Dötz and was extensively developed by his group and W. Wulff's group. They subsequently share the name of the reaction.
The position of the substituents is highly predictable with the largest alkyne substituent (RL) neighboring the phenol and the smallest alkyne substituent (RS) neighboring the methoxy group . Hence, this reaction is more useful for terminal alkynes than internal alkynes.
The phenol can be liberated from the chromium complex by a mild oxidation
, such as ceric ammonium nitrate
or air oxidation.
Since this reaction can quickly generate complex phenolic compounds, the Wulff-Dötz reaction has been used most often in the synthesis of natural product
s, especially Vitamins E
and K
.
from the Fischer carbene complex 1 to give intermediate 3. The loss of CO is rate limiting making the investigation of this reaction mechanism difficult. The alkyne then coordinates to the metal center which has been calculated as a low-energy barrier process with a ΔE‡ of 2.0-4.0 kcal/mol (for terminal alkynes at B3LYP/SVP). The resulting alkyne metal coordinated complex immediately rearranges to intermediate 4 with activation barrier of 3-9 kcal/mol (for terminal acetylenes at B3LYP/SVP). The η1, η3-complex shown as 4 subsequently undergoes CO insertion to give the η4-vinylketene complex 5 which undergoes electrocyclization to give intermediate 6. When R1 is hydrogen, intermediate 6 is short lived and proceeds to the metal tricarbonyl arene complex 2. Without CO insertion, the reaction proceeds through 7 to the cyclopentadiene
product 8.
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
of an aromatic or vinylic alkoxy pentacarbonyl chromium
Chromium
Chromium is a chemical element which has the symbol Cr and atomic number 24. It is the first element in Group 6. It is a steely-gray, lustrous, hard metal that takes a high polish and has a high melting point. It is also odorless, tasteless, and malleable...
carbene complex
Transition metal carbene complex
A transition metal carbene complex is a organometallic compound featuring a divalent organic ligand. The divalent organic ligand coordinated to the metal center is called a carbene. Carbene complexes for almost all transition metals have been reported. Many methods for synthesizing them and...
with an alkyne
Alkyne
Alkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
and carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
to give a Cr(CO)3-coordinated substituted phenol
Phenol
Phenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
. Several reviews have been published. It is named after the German chemist Karl Heinz Dötz (b. 1943) and the American chemist William D. Wulff (b. 1949) at Michigan State University. The reaction was first discovered by Karl Dötz and was extensively developed by his group and W. Wulff's group. They subsequently share the name of the reaction.
The position of the substituents is highly predictable with the largest alkyne substituent (RL) neighboring the phenol and the smallest alkyne substituent (RS) neighboring the methoxy group . Hence, this reaction is more useful for terminal alkynes than internal alkynes.
The phenol can be liberated from the chromium complex by a mild oxidation
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
, such as ceric ammonium nitrate
Ammonium cerium(IV) nitrate
Ceric ammonium nitrate is the inorganic compound with the formula 2Ce6. This orange-red, water-soluble cerium salt is widely used as an oxidising agent in organic synthesis and as a standard oxidant in quantitative analysis....
or air oxidation.
Since this reaction can quickly generate complex phenolic compounds, the Wulff-Dötz reaction has been used most often in the synthesis of natural product
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
s, especially Vitamins E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
and K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
.
Mechanism
The exact details of the Wulff-Dötz reaction are still being discussed and argued. The currently accepted mechanism of this reaction is outlined below. The first step of the reaction involves the loss of carbon monoxideCarbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
from the Fischer carbene complex 1 to give intermediate 3. The loss of CO is rate limiting making the investigation of this reaction mechanism difficult. The alkyne then coordinates to the metal center which has been calculated as a low-energy barrier process with a ΔE‡ of 2.0-4.0 kcal/mol (for terminal alkynes at B3LYP/SVP). The resulting alkyne metal coordinated complex immediately rearranges to intermediate 4 with activation barrier of 3-9 kcal/mol (for terminal acetylenes at B3LYP/SVP). The η1, η3-complex shown as 4 subsequently undergoes CO insertion to give the η4-vinylketene complex 5 which undergoes electrocyclization to give intermediate 6. When R1 is hydrogen, intermediate 6 is short lived and proceeds to the metal tricarbonyl arene complex 2. Without CO insertion, the reaction proceeds through 7 to the cyclopentadiene
Cyclopentadiene
Cyclopentadiene is an organic compound with the formula C5H6. This colorless liquid has a strong and unpleasant odor. At room temperature, this cyclic diene dimerizes over the course of hours to give dicyclopentadiene via a Diels–Alder reaction...
product 8.