Hydroxymethylation conjugate

Conjugate addition, 34-5, 51-2,53, 132, 133 Conjugate hydroxymethylation, 59-60 Copper(n) bromide, 54 Copper([) chloride, 120 Copper(n) chloride, 120 Copper(i) cyanide, 7,52, 53 Copper(i) iodide, 54 Corey s internal quench, 104 Cyanohydrin trimethylsilyl ether, 137 Cycloaddition. 34,112 Cydobutane-l,2-dione, 135 Cyclohept-2-dione, 135 Cyclohex-2-enone, 52,123 Cyclohcxa-1,3-diene, 26 Cyclohexane carboxaldehyde, 22-3,69 73,78... 

Carbofuran in animals may also be hydrolyzed to produce carbofuran-7-phenol. Hydrolysis of the 3-hydroxyderivative leads to formation of 3-hydrocarbofuran-7-phenol. Other degradation products include /V-hydroxymethyl carbofuran and, as in plants, 3-hydroxy- and 3-ketoderivatives. All of these compounds may become conjugated and excreted by animals in urine and, presumably, bile (Metcalf et al. 1968 Finlayson et al. 1979). At least 10 metabolites of carbofuran are known at present their interrelations are shown in detail by Menzie (1978). 

Hydroxymethylation. The reagent undergoes asymmetric conjugate addition to tolylsulfinylcycloalkenones such as 2. The product after reductive desulfinylation (3) and hydrogenolysis furnishes (S)-( - )-3-hydroxymethylcycloalkanones (4) in high enantiomeric purity. 

To achieve these lactose-purpurinimide conjugates 89-93, in the macrocycle positions 3, 8, 12, the purpurin-18-methyl ester 81 had to undergo several chemical transformations to obtain the desired hydroxymethyl group.68 Such alcohol derivatives were reacted with lactose octaacetate in the presence of boron trifluoride diethyl etherate to induce the acetylated lactose-purpurinimide derivative which, after deacetylation reaction conditions, yielded the desired compounds in excellent amounts (Scheme 12). 

The cross-conjugated trienes have potential in many different types of diversification strategies. For example, the triene clearly lends itself to inter- and intramolecular Diels-Alder reactions. Incorporation of the hydroxymethyl group on the tether allows attachment of functionality suitable for reactions subsequent to the Alder-ene reactions. As depicted in Scheme 8.5, propargyl tosylamides A, alkynyl silanes B, acrylate esters C, and propargyl ethers D can all be readily prepared from 39... 

Guanidine carbonate has also been combined with unsaturated 2-hydroxymethyl ketones 882 to give 2-amino-5,6-dihydroquinazolines 883, which were subsequently dehydrogenated to the fully conjugated 2-aminoquinazolines <2002TL3295>. 

The conformational barriers in acyclic radicals are smaller than those in closed-shell acycles, with the barrier to rotation in the ethyl radical on the order of tenths of a kilocalorie per mole. The barriers increase for heteroatom-substituted radicals, such as the hydroxymethyl radical, which has a rotational barrier of 5 kcal/mol. Radicals that are conjugated with a n system, such as allyl, benzyl, and radicals adjacent to a carbonyl group, have barriers to rotation on the order of 10 kcal/mol. Such barriers can lead to rotational rate constants that are smaller than the rate constants of competing radical reactions, as was demonstrated with a-amide radicals, and this type of effect permits acyclic stereocontrol in some cases. "... 

Conjugate aminomethylations of haloalkenes may be achieved by reaction with the hydrogen fluoride-hexamcthylenetetraamine reagent combination. Moreover, acetamidomethylation of some haloalkenes is possible in the hydrogen fluoride medium using jV-(hydroxymethyl)acet-amide.205,2 1 3... 

While there are few examples of conjugate additions of either a-oxygen- or a-silyl-stabilized carbanions, Tamao and Posner have reported two hydroxymethyl synthons ["ClfcOH] (246 and 247) which show synthetic promise. Additions with the silicon-based synthon (246) is restricted to 2-cyclohexen-l-ones and work-up requires a successive acid and base procedure that is incompatible with sensitive molecules,188a-b while the tin-based synthon (247) is more versatile and the hydroxyl group is obtained under neutral conditions (Scheme 83).,88c... 

After peroral administration of 86b, 32—40% of radioactivity appeared in the urine within the First 24-hr period. Another 8—20% appeared during the second 24-hr period, and activity decreased to trace amounts after the second day. Three radioactive metabolites, (hydroxymethyl)dimethylphenylsilane (88), p-trimethyl-silylphenol (89), and an unknown conjugate of 90, could be isolated and characterized (cf. Scheme 9). Metabolism of 87b leads to silanol 91 (90% in the urine within 36 h). 

---