Chugaev Reaction

Chugaev Elimination Reaction and Its Mechanism

The Chugaev elimination reaction is a thermal decomposition reaction in which alcohols form xanthates and then undergo cis-elimination upon heating to generate olefins. Alcohols react with carbon disulfide in the presence of a base (such as sodium hydroxide, sodium hydride, etc.) to form xanthates, which are then methylated with iodomethane or dimethyl sulfate to form xanthates.

The thermal decomposition reaction of xanthates is an E1 process, which undergoes intramolecular oxygen and sulfur hexavalent transition states.

Fig 1. Thermal elimination mechanism of xanthates to olefins. [1]

Characteristics of Chugaev Elimination

The advantage of using the thermal decomposition reaction of xanthates to generate olefins is that the reaction generally does not cause isomerization of the carbon chain skeleton and displacement of the carbon-carbon double bond. For example, in the total synthesis of (+)-vittatine, the C₁-C₂ double bond was successfully constructed by thermal decomposition of xanthates.

It is relatively convenient to prepare olefins using xanthates of secondary and tertiary alcohols. Xanthates of primary alcohols are relatively stable and not easily decomposed by heat. However, for allyl alcohol, its xanthate undergoes [3,3] migration and rearranges to obtain allyl mercaptan compounds.

Stereoselectivity of Chugaev Elimination

The thermal elimination reaction product of xanthate of primary alcohol is unique, while for secondary alcohol, there are both regio- and stereo-selectivity issues. The factor controlling stereoselectivity is that the β-hydrogen must be on the same side (Syn) as the xanthate to facilitate the formation of a six-membered transition state. For example: thermal elimination of threo-1,2-phenyl-1-propanol xanthate will give Z-type olefins; thermal elimination of erythro-1,2-phenyl-1-propanol xanthate will give E-type olefins.

For secondary alcohols with multiple β-hydrogens, stereoselectivity depends on the stability of the six-membered transition state; its regioselectivity is often not high, and only in a more rigid ring structure can a relatively single product be obtained. This greatly limits the application of this method.

Application Examples of Chugaev Elimination

• Example 1: Hiroshi Nakagawa et al. used the simultaneous Chugaev syn elimination reaction and intramolecular ene reaction as key steps to achieve a simple synthetic route from enantiomerically pure (+)-cis-4-benzamido-2-cyclopentenol to (−)-kainic acid. [2]
• Example 2: Shuzhong He et al. proposed a strategy for synthesizing highly functionalized cyclohepta[b]indoles via a concise (4 + 3) cycloaddition-cyclization-elimination sequence. The cycloaddition reaction employed a nitrogen-stabilized oxyallyl cation, while the cyclization and elimination employed an intramolecular Grignard addition and a one-step Chugaev process, respectively. When the tetracyclyl alcohol was treated with a base and CS2, the desired cyclohepta[b]indoles were obtained directly without the need to isolate any xanthate intermediates. [3]
• Example 3: In the formal synthesis of the antitumor diterpene paclitaxel (Taxol), the double Chugaev reaction of the dixanthate from the ABC ring effectively generated the strained bridgehead olefin in excellent yield. [4]

Fig 2. Various synthetic examples via Chugaev elimination.

Related Products

CAS No.	Structure	Product
114686-85-0		2,3-Dichlorophenethyl alcohol
115-69-5		2-Amino-2-methyl-1,3-propanediol
115-84-4		2-Butyl-2-ethyl-1,3-propanediol
52914-23-5		4-Iodophenethyl alcohol
5317-32-8		Piperazin-1-ylpropan-ol
5317-33-9		3-(4-Methyl-1-piperazine)propan-1-ol
25462-23-1		2-Pentylpropane-1,3-diol
54016-70-5		3-Ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide
5402-55-1		2-Thiopheneethanol
5406-18-8		3-(4-Methoxyphenyl)-1-propanol
883-44-3		N-(3-Hydroxypropyl)phthalimide
883267-70-7		2-(2,4,5-trifluorophenyl)ethanol
5339-85-5		2-Aminophenethyl alcohol
5344-27-4		4-Pyridineethanol
53463-68-6		10-Bromo-1-decanol

References

1. Li, J.J. Name Reactions. Springer, Cham., Chugaev Elimination. 2021, pp 86-88.
2. Nakagawa H, et al. Organic letters, 2000, 2(20), 3181-3183.
3. He S, et al. Organic letters, 2014, 16(8), 2180-2183.
4. Fukaya K, et al. Organic letters, 2015, 17(11), 2574-2577.