Glycosylidene Carbenes. Part 24 Reactivity modulation by protecting groups of the addition of glycosylidene carbenes to electron‐rich alkenes

Abstract

The reactivity of glycosylidene carbenes derived from pivaloylated vs. benzylated diazirines 1 and 2 towards enol ethers have been examined. The pivaloylated 1 led to higher yields of spirocyclopropanes than the benzylated 2. Among the enol ethers tested, dihydrofuran 6 proved most reactive, yielding 71 -72% of the spiro-linked tetrahydrofuran 7, while the benzylated diazirine 2 afforded only 33% of the analogue 8 (Scheme 1). Other enol ethers proved much less reactive. The addition of 1 and 2 to the dibydropyran 10 and the 2,3-dihydro-5-methylfuran 15 gave low yields of single cyclopropanes (+ 12, 14, andl6), and the glycals 17 and 18, and (E)-1-methoxyoct-1-ene (23) did not react. The main products of these reactions were the azines (Z,Z)-11 and (Z,Z)/(E,E)-lJ.Similarly, 1 and 2 reacted poorly with (Z)-1-methoxyoct-1-ene (M), leading to the cyclopropanes 25/26/27 and 28/29/30/31 (Scheme 2). Main products were again the azines (Z,Z)-11 and (Z,Z)/(E,E)-13. The structure of 7 and 25 was established by X-ray analysis (Figs. 1 and 2). The mechanism of addition of glycosylidene carbenes to enol ethers is discussed. AM1 Calculations indicate that the LUMO,,,,,,,/HOMO,,,,.,,,,,,, interaction is dominant at the beginning of the reaction, while the transition states are characterized by a dominant interaction of the doubly occupied, sp2-hybridized orbital of the carbene with the LUMO of the enol ether. The relative reactivity of the carbenes towards either the enol ethers or the diazirines determine type and yields of the products.

Ring-Closing Olefin Metathesis of 3,3′-(D-Glycopyranosylidene)bis(1-propene) Compounds as a Route to Anomeric Spiro Sugars

“…Indeed, such compounds had been isolated in trace amounts in the course of our previous investigation 1. Considering that there are only a few scattered synthetically useful routes, based either on free radical2 or on ionic3,4 approaches to C , C ‐disubstituted glycopyranosyl compounds, while access to C , C ‐spirocyclic glycosides5,6 often involves carbene intermediates,7−10 we anticipated that radical‐based allylation of these glycosyl dihalides would be a useful and straightforward method applicable to the synthesis of acetylated 3,3′‐( D ‐glycopyranosylidene)bis(1‐propenes). Such compounds appeared ideally suited for ring‐closing olefin metathesis (RCM)11−13 to afford new unsaturated spiro sugar derivatives.…”

Glycosylidene Diazirines

“…In agreement with the ambiphilic character of alkoxycarbenes, glycosylidene carbenes form cyclopropanes also with electron-rich alkoxyalkenes, provided their reactivity is enhanced by ring tension, such as that in dihydrofuran, that leads to 33% (benzylated diazirine 7) or 72% (pivaloylated diazirine 15) of a single isomer (Figure 5d) [39]. Steric hindrance by an additional methyl group reduces the yield.…”

Investigations of Ring-Opening Reactions of Cyclopropanated Carbohydrates: Towards the Synthesis of the Natural Product (--)-TAN-2483B

“…This substrate has been used as a carbene source for the synthesis of several anomeric spirocyclic cyclopropanes, using olefins such as dihydrofuran and dihydropyran. 37 Another report involved addition of fullerene C…”