Published on: Mar 4, 2016
Transcripts - Prevost Paper222
Prevost trans-Hydroxylation and application in synthesis
This paper describes The Prevost reaction, first proposed in 1933. It also describes a recent
modification of the reaction and shows recent application of the reaction in synthesis of a
Original design of Prevost reaction involves the anti-hydroxylation of alkenes using I2, silver
benzoates and peroxy acids under water free conditions.1 the overall reaction is shown below
(Fig 1). The proposed plausible mechanism involves (Fig 2);
the formation of an iodonium ion by the electrophilic attack of iodine on the electron
rich double bond. Attack of carboxylate group and subsequent intramolecular anti
attack (due to anchimeric assistance) on the electrophilic halo-carbon to form a
Further attack of carboxylate on the resonance stabilized heterocyclic ring leads to the
formation of the diester with anti-configuration, The alkaline hydrolysis of the diester
formed, leads to the formation of the anti-dihydroxyl product. This reaction must
happen in the absence of water.
Figure 1. Overall Prevost reaction. 2
Figure 2. Mechanism of the Prevost Dihydroxylation.3
Importance and Limitation
The Prevost reaction is important because of its stereospecificity and its application in
preparing the trans dihydroxyl isomer. This affords versatility to the synthetic Chemist
compared to the cis-product derived from OsO4. The reaction is also mild, since it doesn’t use
strong oxidizing agents or acids.
The Prevost reaction also needs improvements, if it is to find wide application in organic
synthesis and industry. Some of its disadvantages are: The silver salts used are very
expensive5, the reaction requires a stoichiometric amount of iodine (halogen)4, the reaction
generates a large amount of organic and inorganic waste products. It takes a long time for the
α-iodoacetates to form (1-48hours).5
Modern variation of the Prevost reaction
The usual prevost trans-hydroxylation has been performed with transition metal free
reagents.6 The usual Prevost conditions were invoked, with the cyclic bromonium ion being
formed first. The subsequent reaction of the NaIO4 and the AcOH leads to the production of
water that hinders the formation of the anti-product rather forming the Woodward-Prevost
like Syn-hydroxylation product.
The replacement of NaIO4 with PhI(OAc)2 prevents the formation of water and allows the
formation of the trans hydroxylation product. The mechanism of the modification is shown
There were attempts to obtain the trans-hydroxylation product by using molecular sieves or
anhydrous MgSO4 to remove water formed in situ, this would lead to the formation of the
trans-product from the same reagents used for the syn-hydroxylation. The attempt was
unsuccessful. The use of PhI(OAc)2 instead of NaIO4 led to the formation of the trans-product.
Use of Prevost reaction in Synthesis
A 2-alkyl-4-hydroxypiperidine ((−)-SS20846A) first isolated from Streptomyces sp. has been
synthesized by series of reaction steps including the Prevost reaction. This compound is im-
portant because it shows antibacterial and anticonvulsant properties. The enantiomer of the
compound also shows DNA binding properties, an important step for some biological activi-
Compound 3, a bicyclic heterocycle was obtained after treating the starting material with dif-
ferent reagents in a series of steps;
Step 1: NaH, THF, ii. NaH, 4-bromo-1-butene, LiI, DMF
Step 2: Grubbs’ catalyst, CH2Cl2
Compound 3 was then allowed to undergo Prevost reaction to get the substituted iodo-ben-
zoate shown. The reagent used are I2, silver benzoate, benzene. The stereochemistry of the
trans-product obtained was ascertained by X-ray crystallography.
The diagrams above are all sourced from8
C: I2, silver benzoate, benzene
The most important transformations in this synthetic process involves the cyclization, me-
tathesis to make the piperidine ring, also the 4-hydroxy substitution that is regioselective and
stereo selectively afforded by the Prevost reaction.
Initial discovery of the Prevost reaction has opened the door to a wide variety of modifications
and uses. The overall utilization of this reaction is still widely dependent on a host of
important modifications of the reagents, making the reaction catalytic and allowing the attack
of a wide range of reactants.
1. Prevost, C. Compt. Rend. 1933, 196, 1129.
2. Michaudel Q. (2010). The Scripps Research Institute.
September 24, 2015).
3. Steven F. Organic Mechanisms online.
September 24, 2015).
4. Uemura, S.; Ohe, K.; Fukuzawa, S.; Patil, S.; Sugita, N. Dominant cis-diacetoxylation of
alkenes with tellurium(IV) oxide and lithium bromide in acetic acid. Journal of
Organometallic Chemistry. 1986, 316, pp 67.
5. Myint, Y. Y.; Pasha M. A. Sythesis of α-Iodoacetates from Alkenes by Cadnium Acetate
Catalysed Woodward’s Reaction. Journal of Chemical Research. 2004, 333, May pp
6. Emmanuvel, Lourdusamy; Shaikh,Tanveer Mahammad Ali; Sudalai, Arumugam.
NaIO4/LiBr-mediated Diastereoselective Dihydroxylation of Olefins: A Catalytic Ap-
proach to the Prevost−Woodward Reaction. Organic Letters. 2005, 7, 22, pp 5071-
5074, American Chemical Society, UNITED STATES
7. Maul, C.; Sattler, I.; Zerlin, M.; Hinze, C.; Koch, C.; Maier, A.; Grabley, S.; Thiericke, R.
For isolation of (−)-SS20846A, Journal of Antibiotiotics 1999, 52, pp 1124.