Stereoselection, cyclization enolates

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

Scheme 27 Regioselective and stereoselective cyclization of unsaturated silyl enol ethers.

Hirano et al. reported on the stereoselective cyclization to give tetralin derivatives using the phenanthrene-p-dicyanobenzene sensitizer system. Pandey independently reported the intramolecular photocyclization of methoxybenzene derivatives bearing silyl enol ether chromophore via their heterodimer radical cations in the presence of 1,4-dicyanonaphthalene gave benzo-annulated cyclic ketones in 70% yields [490] (Scheme 133). 

Addition of phenols ArOH to symmetrical alkynes RC=CR, catalysed by [ Au(NHC) 2(//-OH)][BF4] (NHC=A-heterocyclic carbene), has been reported to be (Z)-stereoselective, affording enol ethers R(ArO)C=CHR. a -Coordination of Au(I) to the C=C bond and formation of the phenolate ArOAu has been suggested. An enantioselective domino process, involving the 5-exo-dig cyclization of (178), followed by a second cyclization, giving rise to (179), has been attained by employing a combination of the Au(I) complex (180) and the BINOL-derived phosphoric acid (181) as catalysts (Scheme 11). ... 

Planar ester enol(ate) intermediates which possess axial chirality have been implicated in stereoselective cyclization reactions of methyl (4/ )-3-(2-diazo-3-oxobuta-noyl)-l,l-dioxo-U, 3- (and l-oxo-lA.", 3-) thiazolidine-4-carboxylates. ... 

The intramolecular cyclization of enolate of l-tryptophyl-3-((3-ketobutyl) pyridinium bromide (160) afforded enamine 161, which undergoes stereoselective acid cyclization with cone. HCl to give the pentacyclic ketone 162 (Catalytic hydrogenation of 162 led to (d,l)-pseudoyohimbone (163) (76JA3645). Again, H3-H15 were found to have the tmns configuration in 162. 

The final example concerns cyclization of a silyl enol ether, connected to yet another carbon atom. The (.Ej-enol ether 23 appears to be converted with high stereoselectivity into the aldehyde 24 in 70- 90% yield, while the (Z)-enol ether 23 affords the epimeric aldehyde 25 in similar yield and selectivity164. 

An efficient two-step annelation of functionalized orthoesters with trimethyl-silyloxyfuran derivatives has been reported that produces bicyclo[3. .0]lactones. ° The reaction in Scheme 7 shows an example in which the initial condensation between silyl enol ether and orthoester is followed by the radical cyclization reaction under standard conditions. It is worth underlining the complete diastereocontrol in which three contiguous stereocenters are generated in one step with >95% stereoselectivity. 

Scheme 2.25 shows some examples of additions of enolate equivalents. A range of Lewis acid catalysts has been used in addition to TiCl4 and SnCl4. Entry 1 shows uses of a lanthanide catalyst. Entry 2 employs LiC104 as the catalyst. The reaction in Entry 3 includes a chiral auxiliary that controls the stereoselectivity the chiral auxiliary is released by a cyclization using (V-methylhydroxylamine. Entries 4 and 5 use the triphenylmethyl cation as a catalyst and Entries 6 and 7 use trimethylsilyl triflate and an enantioselective catalyst, respectively. 

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

Clayden and co-workers reported the dearomatiztion of an electron-deficient pyridine ring via intramolecular cyclization of an enolate shown in the scheme above <06OL5325>. Generation of the amino acid derived enolate of 46, with simultaneous activation of the pyridine ring by IV-acylation, leads to a stereoselective transition state 47. The authors postulate that the stereoselectivity arises from the manner in which the bulky PMP (p-... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

The key features of the catalytic cycle are trapping of the radical generated after cycliza-tion by an a,P-unsaturated carbonyl compound, reduction of the enol radical to give an enolate, and subsequent protonation of the titanocene alkoxide and enolate. The diaster-eoselectivity observed is essentially the same as that achieved in the simple cyclization reaction. An important point is that the tandem reactions can be carried out with alkynes as radical acceptors. The trapping of the formed vinyl radical with unsaturated carbonyl compounds occurs with very high stereoselectivity, as shown in Scheme 12.21. 

The isomeric propargylic stannylated aldehyde intermediate, on the other hand, could be prepared from the alcohol precursor without competing cyclization to an seven-membered enol ether product (Eq. 9.105). Treatment of this stannane with SnCl4 afforded the cis-disubstituted tetrahydrofuran stereoselectively. Presumably, this reaction proceeds through an allenyl trichlorostannane intermediate. 

---