Prins reaction intermolecular

The ene and Prins reactions are not mechanistically distinct. Coverage will therefore be organized by the nature of the carbonyl compound, with intermolecular reactions presented first, followed by intramolecular reactions. The emphasis will be on material published since the field has been reviewed " and on examples demonstrating the stereo-, regio- and chemo-selectivity of these reactions. Coverage is restricted to the addition of carbonyl and thiocarbonyl compounds to simple alkenes. Addition of carbonyl compounds to vinylsilanes, allylsilanes and enol ethers is covered in the following chapters. Addition of imines and iminium compounds to alkenes is presented in Part 4 of this volume. Ene reactions with alkenes and alkynes as enophiles are covered in Volume 5, Chapter 1.1. Use of aldehydes and acetals as initiators for polyene cyclizations is covered in Volume 3, Chapter 1.6. 

The direct hydration of Empetal gives only a very poor yield of the desired product because of competing side reactions. These illustrate an important principle in organic chemistry, viz. if an intramolecular reaction can occur to form a 5- or 6-membered ring, then it will usually take precedence over intermolecular reactions. An example in this instance is the intermolecular Prins reaction shown in Figure 3.2. 

In addition to the iminium-salt-based chemistry and to cross-coupling processes, aqueous formaldehyde can also be used as the carbonylated substrate in the Prins reaction, an intermolecular ene-type acid-catalyzed reaction with alkenes providing 1,3-dioxanes (Adams and Bhatnagar, 1977). 

Wender et al. implemented a Prins reaction in the context of a late-stage macrocyclization event. Treatment of allylsilane aldehyde 158 with TMSOTf gave excellent conversion to 20-membered macrocycle 159 (96 % yield). Keck et al. also disclosed a related intermolecular strategy incorporating an allylsilane and an enal. In the presence of TMSOTf, allylsilane 160 and enal 161 led to macrocyclic precursor 162 in an impressive 84 % yield. The highly functionalized substrates used in these examples underscore the mildness of the reaction conditions. 

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. 

The intermolecular Prins cyclization between ketones and homoallylic alcohols can be catalyzed by mercuric triflate <1999TL1153>. TMSNTf2 is an effective catalyst for the reaction between aldehydes and homoallylic alcohols <2002AGE161>. 

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. 

Styrenes are activated in this fashion toward intermolecular Prins-type reaction with 1,1-diaryl alkenes, although at high temperatures (eq 37). ... 

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