TIPS enol ethers

Direct treatment of TIPS enol ethers of a variety of cyclic and acyclic ketones with the strong-base combination of n-BuLi/KO-t-Bu leads to /3-ketosilanes (2) after aqueous work-up. In contrast with the earlier method, this rearrangement appears to proceed through allylic, rather than vinylic, metallation, since enol ethers lacking an allylic a-proton are unreactive. 

Magnus and coworkers have published full details55 on the direct a- or /J-azido functionalization of triisopropylsilyl (TIPS) enol ethers using an iodosylbenzene-TMS-azide combination (equation 13) the w-pathway, favoured at —78 °C, is an azide radical addition process, whereas the -pathway, favoured at —15 to — 20 °C, involves ionic dehydrogenation. Attempts to extend the /3-functionalization to other TMSX derivatives failed. 

Applications of 3 and 4 during the past decade include azidonations of triiso-propylsilyl (TIPS) enol ethers, glycals and dihydropyrans, aryl Ny N-dialkyl-amines, cyclic amides, and cyclic sulfides. Because the relative concentrations of 3 and 4 in solvents employed for their use are uncertain, the azidoiodanes are usually represented collectively as PhIO/TMSN3. 

The reactions of cyclic TIPS enol ethers with PhIO/TMSN3 (1 2) have been examined in detail [12 -14]. Two primary modes of reactivity have been identified, one leading to vicinal-diazides (a-pathway) and the other leading to allylic azides (/1-pathway) (Scheme 3). 

Synthetic applications of the /1-pathway include conversions of the TIPS allylic azides to enones with tetrabutylammonium fluoride, ionization of the C-N3 bond with alkylaluminum reagents and capture of the TIPS enonium ions with carbon nucleophiles, and development of a procedure for y-lactamization [15-17]. Allylic azidonations of TIPS enol ethers have also been incorporated into syntheses of (+)-pancratistatin [18,19] and the core structure of lycorane [20]. 

As observed with the TIPS enol ethers, dihydropyran undergoes either allylic azidonation or frans-diazidonation with PhIO/TMSN3, depending on the reaction conditions (Scheme 5) [21]. These general modes of reactivity have been exploited for the synthesis of diaminopyrans from dihydropyran. Related conversions of 0-protected 3-deoxy- and 3,6-dideoxyglycals to 3-azidoglycals (i.e., allylic azidonation) and their 1-azido isomers have also been reported [22]. 

The /J-azido triisopropylsilyl (TIPS) enol ether (96) functionalization developed by Magnus et al. from TIPS-enol ether (95) using iodosobenzene (Phl=0)-TMSN3 [70-73] provides a unique strategy for the total synthesis of an antitumor agent, (+)-pancratistatin (97) [Eq. (21)]. 

Bis[N-(p-Toluenesulfonyl)]selenodiimide. The reagent obtained from the reaction of chloramine-T with selenium metal, proposed to have structure TsN=Se=NTs, reacts with TIPS enol ethers in an ene-like reaction to give the corresponding a-tosylamino enol ethers (see Eq. 100).345-349... 

Cyclic a, fi-enones. Reaction of triisopropyl (TIPS) enol ethers of cyclic ketones with the combination of C6H5IO and trimcthylsilyl azide in CH2CI2 at -15 provides a /8-azide, which on treatment with Bu4NF at 0° is converted into the o,/8-cnone. Examples ... 

In Magnus studies of jff-azidonation of triisopropylsilyl (TIPS) enol ethers, it was found that addition of TEMPO had a profound effect on the reaction pathway [82]. When TIPS protected enol ether 49 was allowed to react with PhIO and TMSN3 in the absence of TEMPO, compound 51 was obtained as the major product however, in the presence of catalytic TEMPO, compound 53 was obtained (Scheme 27). The formation of product 51 is postulated to occur via conjugate addition of azide anion to an enonium cation intermediate 50, whereas compound 53 is proposed to form via the formation of azide radical, which adds to the silyl enol ether double bond to form intermediate 52. 

Scheme 27. Effect of catalytic TEMPO to the mechanism of addition of trimethylsilyl azide to a TIPS enol ether...

The (3-azidation reaction of triisopropylsilyl enol ethers (Schemes 3.186 and 3.187) has been effectively utilized in organic synthesis [563-565]. Magnus and coworkers have developed a mechanistically different enone synthesis that involves treatment of (3-azido TIPS enol ethers 469 and 471 with fluoride anion to effect desilylation and concomitant (3-elimination to give an a,(3-enone [563]. Alternatively, the (3-azido group in 469 or 471 can be ionized with MesAl or Me2AlCl and the intermediate enonium ion trapped by various nucleophiles, such as an allylstannane, electron-rich aromatics and trimethylsilyl enol ethers, to give various (3-substituted TIPS enol ethers. Reduction of the (3-azido TIPS enol ether provides access to the synthetically useful p-amino TIPS enol ethers [563]. 

The reactions of TBS and TIPS enol ethers of cyclohexanone with trifluoroethyl acrylate and 10 mol% of catalyst 18 in CH2CI2 proceeded smoothly to give [2+2] cycloaddition products 19a-f. Although the endo ester predominated in each case, the selectivity (97 3) was greater for the TIPS enol ether 6a than for the TBS enol ether 5a (82 18) (entries 1 and... 

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