Carbonyl-ene cyclization

The scheme below depicts the novel use of a carbonyl ene cyclization (A, Lewis acid-catalyzed) and a closely related Prins cyclization (B, Brpnsted acid-catalyzed) to generate predominantly trans (cyclization condition A) or cis (cyclization condition B), di and tri substituted piperidines 160 and 161 <06JOC2460 06OBC51>. Of note, in the formation of di-substituted derivatives, R1 = H and R2 = Ph, no reaction occurs under cyclization condition B and the cis isomer 160 is obtained exclusively under cyclization condition A. In the case of tri-substituted derivatives, when bulky substituents at the 2-position (R1 = f-Bu or Ph) are present the trans diastereomer 161 is obtained almost exclusively under cyclization condition A, while no diastereoselectivity is seen under cyclization condition B. 

Enal (54) undergoes intramolecular carbonyl-ene cyclization to give cis- and trans-alcohols (55). Lewis acids such as boron trichloride and tin tetrachloride (and also dimethylaluminium chloride ) give predominantly the cis product, while the preference is reversed with the bulky MeALAr2(Ar = OC6H2 -Br-2, 6-di-Bu ). Open and closed chair-like transition states are considered and compared with previous... 

A -tritylaziridine-2-(5)-carboxaldehyde. The application of a novel, sequential, trans-acetalation oxonium ene cyclization has delivered a stereoselective synthesis of the C-aromatic taxane skeleton, and a combinatorial sequence of the regioselective propiolate-ene, catalytic enantioselective epoxidation and carbonyl-ene cyclization reactions has been used to complete the synthesis of the A-ring of a vitamin D hybrid analogue. 

Mikami et al. reported the first examples of catalytic asymmetric intramolecular carbonyl-ene reactions of types (3,4) and (2,4), using the BINOL-derived titanium complex (1) [46,49], The catalytic 7-(2,4) carbonyl-ene cyclization gives the corresponding oxepane with high enantiopurity, and the gem-dimethyl groups are not required (Scheme 8C.I8). In a similar catalytic 6-(3,4) ene cyclization, tran.v-tetrahydropyran is preferentially obtained with high enantiopurity (Scheme 8C. 19), The sense of asymmetric induction is the same as that observed for the glyoxylate-ene reaction, that is, (R)-BINOL-Ti catalyst provides (R)-alcohol. Therefore, the... 

Scheme 8C.18. Asymmetric 7-(2,4) carbonyl-ene cyclization catalyzed by BINOL-Ti complex.

Enantiopure carbacepham derivatives 54 have been prepared in good yields via Lewis acid promoted carbonyl-ene cyclization of the corresponding 2-azetidinone-tethered alkenylaldehydes 53 (Scheme 18) [63]. 

A novel one-pot tandem oxidation-cyclization-oxidation process was successfully applied in the transformation of unsaturated alcohols 250 [Eq. (5.315)].860 The intermediate aldehyde formed by oxidation with pyridinium chlorochromate (PCC) undergoes a carbonyl-ene cyclization followed by an additional oxidation to form 3-substituted piperidinones. 

Asymmetric carbonyl-ene cyclization of alkenyloxy-substituted aldehydes <9ITL6571> afforded six- and seven-membered cyclic ethers of high enantiomeric purity, for example (/ )-(30) possessed a 91% ee (Equation (10)), when chiral 2,2 -dihydroxy-l,r-binaphthyl-based titanium perchlorate was used as a catalyst. 

Mikami reported a BINOL-Ti-catalyzed asymmetric intramolecular carbonyl-ene cyclization [142], giving the cyclization product with high enantiomeric excess (Scheme 14.56). The sense of asymmetric induction was found to be the same as that for the glyoxylate-ene reaction. This methodology has been successfully applied to the synthesis of analogs of vitamin D3 [143]. 

---