| Prins reaction | |
|---|---|
| Named after | Hendrik Jacobus Prins |
| Reaction type | Coupling reaction |
| Identifiers | |
| Organic Chemistry Portal | prins-reaction |
| RSC ontology ID | RXNO:0000048 |
ThePrins reaction is anorganic reaction consisting of anelectrophilic addition of analdehyde orketone to analkene oralkyne followed by capture of anucleophile or elimination of an H+ ion.[1][2][3] The outcome of the reaction depends on reaction conditions. With water and a protic acid such assulfuric acid as the reaction medium andformaldehyde the reaction product is a1,3-diol (3). When water is absent, the cationic intermediate loses a proton to give anallylic alcohol (4). With an excess offormaldehyde and a low reaction temperature the reaction product is adioxane (5). When water is replaced byacetic acid the correspondingesters are formed.
The original reactants employed by DutchchemistHendrik Jacobus Prins [de] in his 1919 publication werestyrene (scheme 2),pinene,camphene,eugenol,isosafrole andanethole. These procedures have been optimized.[4]
Hendrik Jacobus Prins discovered two new organic reactions during his doctoral research in the year of 1911–1912. The first one is the addition of polyhalogen compound toolefins and the second reaction is the acid catalyzed addition of aldehydes to olefin compounds. The early studies on Prins reaction are exploratory in nature and did not attract much attention until 1937. The development of petroleum cracking in 1937 increased the production of unsaturated hydrocarbons. As a consequence, commercial availability of lower olefin coupled with an aldehyde produced from oxidation of low boiling paraffin increased the curiosity to study the olefin-aldehyde condensation. Later on, Prins reaction emerged as a powerful C-O and C-C bond forming technique in the synthesis of various molecules in organic synthesis.[5]
In 1937 the reaction was investigated as part of a quest for di-olefins to be used insynthetic rubber.
Thereaction mechanism for this reaction is depicted in scheme 5. Thecarbonyl reactant (2) isprotonated by a protic acid and for the resultingoxonium ion 3 tworesonance structures can be drawn. Thiselectrophile engages in anelectrophilic addition with thealkene to thecarbocationic intermediate 4. Exactly how much positive charge is present on thesecondary carbon atom in this intermediate should be determined for each reaction set. Evidence exists forneighbouring group participation of the hydroxyl oxygen or its neighboring carbon atom. When the overall reaction has a high degree ofconcertedness, the charge built-up will be modest.
The three reaction modes open to thisoxocarbenium intermediate are:
Many variations of the Prins reaction exist because it lends itself easily to cyclization reactions and because it is possible to capture the oxo-carbenium ion with a large array of nucleophiles. The halo-Prins reaction is one such modification with replacement of protic acids and water bylewis acids such asstannic chloride andboron tribromide. Thehalogen is now thenucleophile recombining with the carbocation. The cyclization of certainallyl pulegones inscheme 7 withtitanium tetrachloride indichloromethane at −78 °C gives access to thedecalin skeleton with the hydroxyl group and chlorine group predominantly incis configuration (91% cis).[7] This observed cisdiastereoselectivity is due to the intermediate formation of a trichlorotitaniumalkoxide making possible an easy delivery of chlorine to the carbocation ion from the same face. The trans isomer is preferred (98% cis) when the switch is made to atin tetrachloride reaction atroom temperature.
The Prins-pinacol reaction is acascade reaction of a Prins reaction and apinacol rearrangement. The carbonyl group in the reactant inscheme 8[8] is masked as a dimethylacetal and thehydroxyl group is masked as atriisopropylsilyl ether (TIPS). With lewis acidstannic chloride theoxonium ion is activated and the pinacol rearrangement of the resulting Prins intermediate results in ring contraction and referral of the positive charge to the TIPS ether which eventually forms analdehyde group in the final product as a mixture of cis and trans isomers with modest diastereoselectivity.
The key oxo-carbenium intermediate can be formed by other routes than simple protonation of a carbonyl. In a key step of the synthesis of exiguolide, it was formed by protonation of avinylogous ester:[9]
