Tetramethylpiperidine cleavage

First the interaction of selected tetramethylpiperidine (TMP) derivatives with radicals arising from Norrish-type I cleavage of diisopropyl ketone under oxygen was studied. These species are most probably the isopropyl peroxy and isobutyryl peroxy radicals immediately formed after a-splitting of diisopropyl ketone and subsequent addition of O2 to the initially generated radicals. Product analysis and kinetic studies showed that the investigated TMP derivatives exercise a marked controlling influence over the nature of the products formed in the photooxidative process. The results obtained point to an interaction between TMP derivatives and especially the isobutyryl peroxy radical. 

Cyclohexenones 34 also undergo a highly diastereoselective dihydroxylation to give cii-diols 39 (Scheme 11).22 These diol amides are converted to hydroxylactones 40 by an acid-catalyzed process involving retro aldol-realdolization prior to transacylation. The enantiomers of hydroxylactones 40 are obtained from iodolactones 35 by iodide exchange with 2,2,6,6-tetramethylpiperidin-l-yloxy free radical (TEMPO) followed by reductive cleavage of the TEMPO derivative with Zn in ElOAc. The enantiomeric purity of the hydroxylactones prepared by either route is 95-98% ee. 

In all the examples given so far, the substrate carries at least one V-o -hydrogen atom. The anodic oxidation of fully substituted amides, like N, V-di-/cr/-butylformamide and V-formyl-2,2,6,6-tetramethylpiperidine, in MeOH would be expected to follow a different pathway. The products isolated after 12-14 F, methyl V-/cr/-butylcarbamate and V-methoxycarbonyl-2,2,6,6-tetramethylpiperidine, respectively [Eq. (37)] [102], indicated that the primarily formed substrate radical cation looses the formyl proton. Further oxidation of the neutral radical leads to the cation, which may either undergo cleavage, as in Eq. (38), or nucleophilic attack by the solvent, as in Eq. (39). 

Gallc er and co-workers devised a formal enantioselective synthesis of ( — )-3 in wduch the stereogenic center at C-6 was derived fiom Cbz-protected (S)-2-amino-4-pentenoic acid (36) (44). Acylation of 3,3-dimethoxy-pyrrolidine (37) with this acid yielded amide 38, which was converted into aldehyde 39 by cleavage of the terminal alkene vnth osmium tetroxide and sodium periodate (Scheme 5). The indolizidine nucleus was constructed from 39 by a problematic intramolecular aldol condensation, which was eventually optimized by using 2,2,6,6-tetramethylpiperidine as base followed by adsorption onto, and elution from, silica gel (45). Diastereoselective reduction of the ketone group of the aldol product 40 was accomplished in better than 95% enantiomeric excess (ee) with the Corey... 

The Hosomi-Sakurai-Prins reaction of the easily available enal 142 and allylsilane 143 was performed in the presence of Lewis acids to give the 4-methylene-tetrahydropyran with poor cis-trans selectivity ( 2 1), however, the pro tic acid provided only cis-144, which was converted into the aldehyde 145. The Takai iodoalkenylation, followed by desilylation and Sharpless asymmetric epoxidation, provided 146 with a 4 1 ratio of /Z, which was separable via the treatment of TBAE After protection of the primary alcohol, the alkenyllithium derived from the iodoalkene, reacted with aldehyde 147 to form 148, which was converted into epoxy-carboxylic add 149 in five steps. The key macrocyclization was performed by the treatment of 149 with Ti(Oi-Pr)4 [73] under high diluted conditions (2 mM) at 75 °C to provide the macrolactone 150 in moderate yield with 30% of the starting material recovery. After desilylation, the chemoselective oxidation of the allyl alcohol with 4-acetylamino-2,2,6,6-tetramethylpiperidine- 1-oxoammonium tetraflu-oroborate, followed by oxidative cleavage of the C20-C21 diol, produced (-)-dactyloUde (Scheme 30). 

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