Silylative Dieckmann-Like Cyclizations of Ester-Imides (and Diesters)

Abstract

[Structure: see text] Trialkylsilyl triflates effect cyclization of ester-imides such as 2 to produce adducts such as 4a. Trapping of the in situ generated, nucleophilic ketene acetal (cf. 5a) is a key aspect of the transformation. A range of substrates amenable to this operationally simple reaction is reported. In many instances the levels of diastereoselectivity are very high. Mechanistic points are inferred from spectroscopic observations.

Synthesis of Spirocyclopropyl γ‐Lactams by a Highly Stereoselective Tandem Intramolecular Azetidine Ring‐Opening/Closing Cascade Reaction

“…Not surprisingly, conversion of 12 provided the expected spirocyclopentane 14 as the increase of the alkyl chain length by one methylene unit favored the Dieckmann reaction (Scheme ). Further increase in the alkyl chain length by two methylene units to favor azetidine ring opening (formation of a six‐membered ring) over the Dieckmann reaction (formation of a disfavored seven‐membered ring)9a led to substrate 13 , which was not reactive under our typical cyclization conditions. The influence of steric effects on the cyclization process was explored with tert ‐butyl ester 15 , which afforded the expected spiranic lactam in a much lower yield than that of corresponding methyl ester analog 5 (Scheme ).…”

“…We then turned our attention to a cationic variant of the Dieckmann reaction involving a silyl ketene acetal generated by treatment of enolizable ester 5 with TMSOTf and triethylamine (TEA) 9. In a first attempt, reaction of 5 following Hoye's protocol9a did not lead to the formation of theDieckmann product but to functionalized 5‐azaspiro[2.4]heptane derivative 6a in 65 % yield as a single diastereoisomer (Scheme ). The 5‐azaspiro[2.4]heptane skeleton is a motif present in various biologically active molecules including antibacterial and antiautoimmune agents 10,11…”

Anionic Cascade Reaction Followed by Silylative Dieckmann Cyclization: A Straightforward Route to Tricyclic Fused Ring Systems Starting from Alkynyl Esters Tethered to Bicyclo[n.2.0]alkanones

“…[18] Nevertheless, an acidic Dieckmann condensation was considered as a valuable alternative in this case. [17] We were delighted to find that the addition of a mixture of TBSOTf/ NEt 3 to α,ω-diester 16 led quantitatively to the tricyclic derivative 31, with a total diastereoselectivity. This is probably because a unique Z-ketene silyl acetal 16a was formed.…”

Synthetic Strategies towards the Azabicyclo[3.3.0]-Octane Core of Natural Pyrrolizidine Alkaloids. An Overview

“…At the same time, similar results were also reported by Hoye et al, whereby various substituted pyrrolizidines were obtained (72-97% yields). 223 …”