Reactions Prins

The Prins reaction is the acid-catalyzed addition of aldehydes to alkenes and gives different products depending on the reaction conditions. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 208, Springer-Verlag Berlin Heidelberg 2009 

Weekblad 1919, 16, 1072—1023. Bom in Zaandam, The Netherlands, Hendrik J. Prins (1889-1958) was not even an organic chemist per se. After obtaining a doctorate in chemical engineering, Prins worked for an essential oil company and then a company dealing with the rendering of condemned meats and carcasses. But he had a small laboratory near his house where he carried out his experiments in his spare time, which obviously was not a big distraction—for he rose to be the president-director of the firm he worked for. 

Braddock, D. C. Badine, D. M. Gottschalk, T. Matsuno, A. Rodriguez-Lens, M. Synlett 2003, 345-348. 

Sreedhar, B. Swapna, V. Sridhar, Ch. SaHeela, D. Sunitha, A. Synth. Commun. 2005, 55, 1177-1182. 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 223, Springer International Publishing Switzerland 2014 

The separation of the reaction products—i.e. the oxidation product and the carboxylic acid—can usually be achieved by extraction with mild aqueous base. 

A modern reagent, that has found increased application, is dimethyldioxirane it is prepared in situ by oxidation of acetone with potassium peroxomonosul-fate KHSOs.  

The epoxidation reaction usually takes place under mild conditions and with good to very good yield. Functional groups that are sensitive to oxidation should not be present in the starting material with carbonyl groups a Baeyer-Villiger reaction may take place. 

The acid-catalyzed addition of an aldehyde—often formaldehyde 1—to a carbon-carbon double bond can lead to formation of a variety of products. Depending on substrate structure and reaction conditions, a 1,3-diol 3, allylic alcohol 4 or a 1,3-dioxane 5 may be formed. This so-called Prins reaction often leads to a mixture of products. 

The initial step is the protonation of the aldehyde—e.g. formaldehyde—at the carbonyl oxygen. The hydroxycarbenium ion 6 is thus formed as reactive species, which reacts as electrophile with the carbon-carbon double bond of the olefinic substrate by formation of a carbenium ion species 7. A subsequent loss of a proton from 7 leads to formation of an allylic alcohol 4, while reaction with water, followed by loss of a proton, leads to formation of a 1,3-diol 3  

Coates et al. reported the Lewis acid-mediated Prins cyclization of 8,e-unsaturated ketones [49]. It was shown that TiCU, TiBr4, BCls and BBr3 promoted syn-selective cyclization to produce sterically congested cis-halohydrins, whereas SnCU, SnBr4, 

5 Carbonyl Activation Reactions Including Mukaiyama-Type Reactions 533 SnCU, SnBr4, ZrC or InCIa 

Wang et al reported Lewis acid-controlled regioselective 1,2- and 1,4-addition reactions of a,P-unsaturated ketones with Ti(IV) enolates [51] derived from 

5 Carbonyl Activation Reactions Including Mukaiyama-Type Reactions 535 

Uno et oL reported a Mukaiyama-type aldol reaction of l-tcrt-butoxycarbonyl-2-(tert-butyldimethylsiloxy)pyrrole with aliphatic or aromatic aldehydes in the presence of BF3 Et20 to give the corresponding erythro- or threo-isomers, respectively 

Studies toward the biomimetic total synthesis of (+)-chatancin were conducted by P. Deslongchamps et al. The authors planned to use a transannular Diels-Alder reaction of a pyranophane intermediate as the key ring forming step. The cyclic dienedione precursor for this transformation was prepared using the Prins reaction on a substrate derived from trans-trans farnesol. 

The tandem Mukaiyama aidoi reaction-Prins cyciization was utilized during the formal total synthesis of leucascandrolide A by S.D Rychnovsky. The addition of the activated aldehyde to the enol ether resulted in the formation of an oxocarbenium ion, which was captured intramolecularly by the allylsilane moiety to form a new tetrahydropyran ring. The reduction of the crude reaction mixture with NaBH4 was performed to remove the unreacted aldehyde starting material, thereby facilitating the chromatographic purification of the product. The product was isolated as a 5.5 1 mixture of epimers at C9. 

In the laboratory of R.D. Rychnovsky, the segment-coupling Prins cyciization was utilized for the total synthesis of (-)-centrolobine. This approach avoided the common side reactions, such as side-chain exchange and partial racemization by reversible 2-oxonia Cope rearrangement, associated with other Prins cyciization reactions. The substrate -acetoxy ether was subjected to SnBr4 in DCM, which brought about the formation of the all-equatorial tetrahydropyran in good yield. 

The stereoselective total synthesis of ( )-isocycloseychellene was achieved by S.C. Welch and co-workers. One of the key ring forming reactions was an oxidative Prins reaction that took place without the need of a catalyst (carbonyl ene reaction) to afford the desired tricyclic ketone. 

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PdCb-CuCb catalyzes the condensation of branched-chain alkenes with formaldehyde to give the l,3-dioxanes 96a and 96b (Prins reaction)[73]. The yields are much higher than in the conventional acid-catalyzed Prins reaction. 

Prince William Sound Prinivil Prins reaction Print bonding Printed circuit board... 

An important synthetic process for forming a new carbon—carbon bond is the acid-catalyzed condensation of formaldehyde with olefins (Prins reaction) ... 

A commercial process based on the Prins reaction is the synthesis of isoprene from isobutylene and formaldehyde through the intermediacy of 4,4-dimethyl-l,3-dioxane (49—51) ... 

Uses ndReactions. Some of the principal uses for P-pinene are for manufacturing terpene resins and for thermal isomerization (pyrolysis) to myrcene. The resins are made by Lewis acid (usuaUy AlCl ) polymerization of P-pinene, either as a homopolymer or as a copolymer with other terpenes such as limonene. P-Pinene polymerizes much easier than a-pinene and the resins are usehil in pressure-sensitive adhesives, hot-melt adhesives and coatings, and elastomeric sealants. One of the first syntheses of a new fragrance chemical from turpentine sources used formaldehyde with P-pinene in a Prins reaction to produce the alcohol, Nopol (26) (59). 

Uses ndReactions. The Prins reaction of 3-carene with formaldehyde in acetic acid gives mainly 2-carene-4-methanol acetate, which when saponified produces the 2-carene-4-methanol, both of which are commercial products of modest usage (60). 3-Carene (28) also reacts with acetic anhydride with a catalyst (ZnCl2) to give 4-acetyl-2-carene (29) (61), which is also a commercial product. Although 3-carene does not polymerize to produce terpene resins, copolymerization with phenol has been successfully commercialized by DRT in France (62). 

The Prins reaction with formaldehyde, acetic acid, acetic anhydride, and camphene gives the useful alcohol, 8-acetoxymethyl camphene, which has a patchouli-like odor (83). Oxidation of the alcohol to the corresponding aldehyde also gives a useful iatermediate compound, which is used to synthesize the sandalwood compound dihydo- P-santalol. 

Longifolene. There are at least four commercially important aroma chemicals made from (+)-1ongifo1ene and about thirteen products made from (-)-isolongifolene (90) (182). Acetoxymethyl longifolene or the formate are formed during the Prins reaction on (+)-1ongifo1ene. Saponification of the esters gives the useful perfumery alcohol (183) (Fig. 9). 

The Prins reaction on isolongifolene has also produced a number of useful products (185,186). All the products have amber, woody odors, and are known under the names of Amborol, Amboryl Formate, and Amboryl Acetate. 

Condensation of vinyl chloride with formaldehyde and HCl (Prins reaction) yields 3,3-dichloro-l-propanol [83682-72-8] and 2,3-dichloro-l-propanol [616-23-9]. The 1,1-addition of chloroform [67-66-3] as well as the addition of other polyhalogen compounds to vinyl chloride are cataly2ed by transition-metal complexes (58). In the presence of iron pentacarbonyl [13463-40-6] both bromoform [75-25-2] CHBr, and iodoform [75-47-8] CHl, add to vinyl chloride (59,60). Other useful products of vinyl chloride addition reactions include 2,2-di luoro-4-chloro-l,3-dioxolane [162970-83-4] (61), 2-chloro-l-propanol [78-89-7] (62), 2-chloropropionaldehyde [683-50-1] (63), 4-nitrophenyl-p,p-dichloroethyl ketone [31689-13-1] (64), and p,p-dichloroethyl phenyl sulfone [3123-10-2] (65). 

Formaldehyde also reacts with butadiene via the Prins reaction to produce pentenediols or their derivatives. This reaction is cataly2ed by a copper-containing catalyst in a carboxyUc acid solution (57) or RuCl (58). The addition of hydrogen also proceeds via 1,2- and 1,4-addition. 

The Prins reaction often yields stereospecifically the and-addition product this observation is not rationalized by the above mechanism. Investigations of the sulfuric acid-catalyzed reaction of cyclohexene 8 with formaldehyde in acetic acid as solvent suggest that the carbenium ion species 7 is stabilized by a neighboring-group effect as shown in 9. The further reaction then proceeds from the face opposite to the coordinating OH-group " ... 

The formation of complex mixtures of products by a Prins reaction can be a problem. An example is the reaction of aqueous formaldehyde with cyclohexene 8 under acid catalysis ... 

Scheme 1). Introduction of a jt bond into the molecular structure of 1 furnishes homoallylic amine 2 and satisfies the structural prerequisite for an aza-Prins transform.4 Thus, disconnection of the bond between C-2 and C-3 affords intermediate 3 as a viable precursor. In the forward sense, a cation ji-type cyclization, or aza-Prins reaction, could achieve the formation of the C2-C3 bond and complete the assembly of the complex pentacyclic skeleton of the target molecule (1). Reduction of the residual n bond in 2, hydro-genolysis of the benzyl ether, and adjustment of the oxidation state at the side-chain terminus would then complete the synthesis of 1. 

This type of polyhalo alkane adds to halogenated alkenes in the presence of AICI3 by an electrophilic mechanism. This is called the Prins reaction (not to be confused with the other Prins reaction, 16-53). ... 

The addition of an alkene to formaldehyde in the presence of an acid catalyst is called the Prins reaction.Three main products are possible which one predominates depends on the alkene and the conditions. When the product is the 1,3-diol or the dioxane, the reaction involves addition to the C=C as well as to the C=0. The mechanism is one of electrophilic attack on both double bonds. The acid first protonates the C=0, and the resulting carbocation attacks the C=C ... 

The Prins reaction has also been carried out with basic catalysts Griengl, H. Sieber, W. Monatsh. Chem., 1973, 104, 1008, 1027. 

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