Factors Controlling the Alkyne Prins Cyclization: The Stability of Dihydropyranyl Cations

Abstract

The relative stability of the intermediates involved in the alkyne Prins cyclization and the competitive 2-oxonia-[3,3]-sigmatropic rearrangement was studied. This rearrangement was shown to occur slowly under typical alkyne Prins cyclization conditions when the allenyl oxocarbenium ion that results from the rearrangement is similar to or higher in energy than the starting alkynyl oxocarbenium ion. The formal 2-oxonia-[3,3]-sigmatropic rearrangement may be disfavored by destabilizing the resultant allenyl oxocarbenium ion or by stabilizing an intermediate dihydropyranyl cation. The trimethylsilyl group as a substituent at the alkyne and electron-withdrawing groups (CH2Cl and CH2CN) located at the alpha-position to the carbinol center are shown to be effective. DFT calculations suggest that these substituents stabilize the dihydropyranyl cations, thus leading to a more uniform reorganization of the electronic density in the ring, and do not have a direct effect on the formally positively charged carbon atom.

Intramolecular alkyne–dithiolium cycloaddition: a joint experimental and DFT mechanistic study

“…This is a mechanism typical of the Prins-type cyclization reactions. [44][45][46][47][48][49] The transition state of this process (11-TS1) clearly reveals a new s bond formed between C1-C2 (see Fig. 2 and Table 2), but the distances at C3-C4 and C3-C5 (3.60Å and 3.65Å) are, in contrast to the case of 10, beyond the van der Waals contact and hence indicate little covalent interactions.…”

“…The rst reaction pathway is a concerted 1,3-dipolar cycloaddition 39,40 that directly leads to a cage-shaped intermediate IM-3 with the backbones of B and C rings assembled simultaneously. The second one is a stepwise pathway, in which the alkynyl group attacks the carbocation of dithiolium ring via an alkyne Prinstype cyclization [44][45][46][47][48][49] at rst. The electrophilic cyclization occurs with a 5-exo-dig regioselectivity, forming the B ring only.…”

Synthesis of Halogenated Cyclic Enamines from Cyclic N‐2‐En‐4‐ynyl‐N‐1‐ynylamides and N‐Propargyl‐N‐1‐ynylamides via a Tandem Iron Halide Promoted N‐to‐C Shift‐Aza‐Prins Cyclization Sequence

“…Other Lewis acids, for example, AlCl 3 , FeBr 3 , FeCl 2 , TMSCl, and InCl 3 were also screened. Among them, only AlCl 3 and FeBr 3 gave low conversions to the cyclized product 2 a and the corresponding brominated bridged bicyclic enamine, respectively ( 13). Moreover, when the five-membered ring analogue 3 a was treated with 6 M aq HCl (9 equiv.…”

“…A formal alkyne aza-Prins cyclization reaction path [13] is suggested for the formation of cyclobutenamine 10 a (Scheme 4). An N-to-C propargyl shift of 9 a with FeBr 3 leads to ketenimine 11.…”

Strategies for the Synthesis of Cyclic Ethers of Marine Natural Products

“…The calculations also showed that the trimethylsilyl group does not have a direct effect on the formally positively charged carbon atom. 84 To confirm that no racemization occurred during the cyclizations to the tetrasubstituted dihydropyrans, we treated alcohol (R)-134 with phenylacetaldehyde and iron(III) chloride. The resulting dihydropyran 135 showed a slightly reduced but still synthetically useful enantiomeric purity compared with the starting homopropargylic alcohol (R)-134 (Scheme 48).…”