Prins reaction control

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. ... 

Double Prins reactions use ofSn and Si to control cation formation Hydroboration as a Way to Make Carbon-Carbon Bonds Carbonylation of Alkyl Boranes... 

The next step is a simple electrophilic attack by another molecule of formaldehyde on the alkene - in other words a simple Prins reaction 215 - showing the regioselectivity we expect to produce the secondary benzylic cation 216. The second molecule of formaldehyde has added onto the opposite side from the first. The resulting cation is perfectly placed for an intramolecular Friedel-Crafts alkylation 216 of the benzene ring. This is again a stereoselective reaction giving the more stable anti diastereoisomer 214. This sequence involves three successive C-C bondforming reactions and the stereochemistry is simply controlled by the preference for the more stable anti product. 

Double Prins reactions use of Sn and Si to control cation formation... 

One problem with the original Prins reaction was uncertainty in the fate of the cation 189. Recent advances have used the chemistry of allyl tins and silanes explored in chapter 12. For example addition of aldehydes to reagent 218 with a chiral catalyst formed from BINOL (chapter 26) and Ti(0/-Pr)4 gave the allyl silane 219. This in turn reacted with a second aldehyde using an achiral Lewis acid to give the THPs 220. Yields are very high, enantiomeric excess almost perfect (90-96%) and various aromatic, enolisable aliphatic and functionalised aldehydes can be used in both steps. Control expressed in the isolation of the stable intermediate 219 means that the two aldehydes need not be the same.36... 

The problem with the Prins reaction itself, and the reason that it plays such an inconspicuous part in organic synthesis, is the difficulty in controlling the outcome the cation (2) can, and usually does, suffer... 

Potassium decanoate, 359 Potassium permanganate, 274 Potassium soaps, 328,359,361 Potato lipoxygenase, 458 Poultry adipose tissue, 556 Pre-pressing, 186 Premier jus, 98,124 see also Beef tallow Primary alcohol esters, 143 Primary alcohols, 146 Prins reaction, 476 Pristane, occurrence, 138,148 Pristanic acid, 16 Process control, 217 Procetofen, 540 Production control, 217 Production of oils and fats fish oils, 130 butter, 219... 

The role of formaldehyde dimer in 0-containing heterocycles formation by the Prins reaction have been investigated. It was shown that the 1,3-di-oxanes, hydrogenated pyrans and oxetanes can be can be obtained from formaldehyde dimers and alkenes in the gas phase. The activation energy of these reactions is different. It is lower for 1,3-dioxanes formation, and higher for oxetanes formation. Thus formation of 1,3-dioxanes happens in the conditions of kinetic control. Opposite, the hydrogenated pyrans formation happens in the conditions of thermodynamic control... 

In addition to characterizing a catalytically active material under dynamic reaction conditions, the method has been used to characterize the structural evolution taking place during the preparation of active catalysts from precursor materials. Either a DXAFS spectrometer (Fiddy et al., 2002 Hatje et al., 1994 Sankar et al., 1992 Sankar et al., 1993 Shido et al., 2002 Thomas et al., 1994 Yamaguchi et al., 2000, 2002) or the QEXAFS mode at a conventional XAFS beam line (Cimini and Prins, 1997 Wienold et al., 2003) was employed. Because a controlled thermal treatment of a precursor material permits a better tailoring of the time... 

Two independent reports have appeared that detail methodology for the introduction of pyran or oxepene spirocychc moieties onto oxindole scaffolds by means of a Prins cyclization (Scheme 35). In one study by Zhang and Panek, treatment of isatin dimethylketal 134 with sUyl alcohol (S )-135 afforded predominately c -137 or trans-Vi9 depending on reaction time and solvent polarity [78]. A mechanism involving epimerization of the cis-product to the trans adduct was put forward to explain the observed frans-selectivity with increased reaction time in polar solvents. A cyclic transition state involving a (Z)-oxonium intermediate formed via condensation of silyl alcohol 135 with isatin 134 was invoked to rationalize the preferential formation of the cis-spirocycle under kinetic control. Further optimization led to the formation of spirooxindoles 138, e.g., R, = Me, as single... 

The synthesis of the as-fused butyrolactone tetrahydropyran core of (-b)-Greek tobacco lactone involves an intramolecular oxa-Michael reaction of a furan-3-en-2-one bearing a propanediol chain at C-5 (14SL1888). Prins cyclization of ( /Z)-6-mercaptohex-3-en-l-ol with aliphatic and aromatic aldehydes is condition-controlled stoichiometric amounts of strong Lewis or Bronsted acids afford mainly thiophen[c]-fused tetrahydropyrans whereas catalytic amounts of weak Lewis or Bronsted acids provide furan[c]-fiised tetrahydrothiopyrans as major products (Scheme 13)... 

Loh et al. developed another crossed Prins cyclization procedure using InCls by careful control of conditions and reactant ratios throughout the reaction [206]. Compared to the earlier requirements for stoichiometric proportions reported by Li et al. [199], the use of InCb was reduced to catalytic levels by using allylchlorosilane as the allylating agent (Figure 8.91). 

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. 

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