Prins addition reactions

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). 

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

Quite recently, a domino Diels-Alder/Prins/pinacol reaction was reported by Barriaulfs group [38]. This novel method is very reliable and efficient for the synthesis of highly functionalized bicyclo[m.n.l]alkanones. In addition, Aube and coworker [39] used a combination of a Diels-Alder and a Schmidt reaction within the total synthesis of the Stemona alkaloid stenine [40]. 

A novel gold catalyzed example of three-component addition was recently reported by Shi et al. (Equation 8.44) [106]. Terminal aryl alkynes, alcohols and 2-(arylmethy-lene) cyclopropylcarbinols provided an intermolecular tandem hydroalkoxylation/ Prins-type reaction to form 3-oxabicyclo[3.1.0]hexanes from simple materials and under mild conditions, catalyzed by the system AuClPPh3/AgOTf. The proposed mechanism for this reaction is shown in Scheme 8.19. 

This rule states that all bonds being made or broken in a concerted reaction should preferably be coplanar and aligned in a trans, anti geometry relative to each other. The explanation for this lies in the molecular orbitals involved. As illustrative examples, let us look first at the Prins addition of formaldehyde to 1,1-dimethylbuta-1,3-diene (5.39) and then at the elimination of water from an alcohol. 

Other acid-catalysed addition reactions include reaction with nitriles (Ritter reaction), formaldehyde (Prins reaction) and carbon monoxide and water (Koch reaction). These reactions are normally catalysed by concentrated sulphuric acid. Extensive isomerization occurs and may even lead to quaternary compounds of the type RC(CH3)XR where X is the new functional group introduced into the molecule. Homogeneous catalysts have been developed which give simpler products without extensive isomerization. 

ABSTRACT. Aldehydes, ketones and a,p-unsaturated aldehydes and ketones undergo a wide variety of reactions with unactivated alkenes in the presence of alkylaluminum halide catalysts. Ene reactions, Diels-Alder reactions, Prins reactions and cation-olefin addition reactions occur depending on the choice of substrate and Lewis acid. 

The side products obtained in Lewis acid catalyzed ene reactions of formaldehyde with mono-and 1,2-disubstituted alkenes are consistent with the mechanistic scheme shown in Figure 2. When only 1 equivalent of Me2AlQ is used chloro alcohols are formed as by products. When excess Lewis acid is used chloroalcohols are fonned as transient intermediates which are converted to ene adducts and other products. The chloroalcohols formed from 1,2-disubstituted alkenes result from the stereospecifically cis addition of the hydroxymethyl and chloride groups to the double bond. This result was unexpected since all previous Prins additions have been shown to proceed predominantly by trans addition. 4 Cis addition of chloride and hydroxymethyl groups would be expected from intermediates such as 4 or 5 and 6. 

The gold(I)-catalyzed intermolecular addition of carbonyl compounds to 1,6-enyne 1-9 presumably proceeds by trapping rearranged gold carbene intermediate 1-12 with the carbonyl compounds (Scheme 2.4). Thereby forming the oxonium cation 1-13, which undergoes a Prins-type reaction to give I-IO, probably via intermediate 1-14. 

Floreancig and coworkers employed a sequential Peterson olefmation and Prins cyclisation reaction in their total synthesis of (+)-dactylolide hence neatly illustrating the versatility of the Peterson reaction. The P hydroxysilane 103 was synthesised in situ by the double addition of the necessary Grignard reagent onto ester 102. Treatment of the resulting tertiary alcohol with pyridinium triflate and magnesium sulfate then prompted the Peterson olefmation and subsequent Prins cyclisation to occur, affording tetrahydropyran 106 in 75% yield. 

Because of these interesting biological activities and the scarcity of materials from their natural sources through isolation, great emphasis has been placed on synthetic approaches toward the efficient construction of tetrahydropyrans. These approaches include the Prins and related cyclization reactions, the hetero-Diels-Alder cyclizations, radical cyclizations, transition metal mediated cyclizations, as well as more traditional methods such as epoxide-mediated cyclizations and oxa-conjugate addition reactions. 

In 2001, Rychnovsky and co-workers completed the synthesis of the leucascandrolide macrolactone. The key features of the Rychnovsky s synthesis are the Mukayama aldol-Prins cascade reaction of alkyl enol ether with the aldehyde forming 2,6-cij-tetrahydropyran, and Hosomi-Sakurai allysilane addition to generate 2,6-tranj-tetrahydropyran (Schemes 2.12, 2.13). 

Indium Lewis acids have garnered attention due to their mild reactivity and air and water stability. Both Li et al. and Chan and Loh have shown that In(III) complexes are suitable Lewis acids for Prins cyclizations [81, 82]. These reports prompted Loh and coworkers to embark on a synthesis of (+)-SCH 351488 that utilized this strategy (Scheme 40) [83]. Condensation of homoallylic alcohol 147 and aldehyde 148 in the presence of indium ttibromide and TMSBr gave 4-bromo THP 149 in 65 % overall yield as an inconsequential mixture of diastereomers (2,A-cisP,4 trans = 75 25). Complete retention of the homoallylic alcohol stereochemistry is responsible for the key 2,6-cis relationship in the product. Initial attempts to apply these same conditions to the B ring resulted in acetonide deprotection and no THP formation. Subsequent optimization revealed that indium triflate and TMSCl were competent additives to effect cyclization. Careful temperature control was required to suppress an undesired Prins side reaction. The combination of homoallylic alcohol 150 and aldehyde 151 in the presence of the appropriate Lewis acids at 78 °C, followed by warming to 0 °C for 4 h, led to the desired monomer precursor 152 in 42 % yield. 

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 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 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 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 ... 

Protonic acid and Lewis acids can activate carbonyls to facilitate the addition of nucleophile attacks in aqueous media. The Prins reaction, reaction with alkyne, and Friedel-Crafts-type reactions have been discussed in related chapters in detail. 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

Other nucleophilic additions conducted in aqueous media can be found in the literature (Lubineau et al., 1994 Strauss, 1999). These reactions will include the benzoin condensation, the Prins reaction, and the Wittig-Horner reaction, and the Baeyer-Villi-ger oxidation. 

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