Synthesis of Alkylidene(gem-Difluorocyclopropanes) from Propargyl Glycolates by a One-Pot Difluorocyclopropenation/Ireland–Claisen Rearrangement Sequence

Abstract

A one-pot difluorocyclopropenation/Ireland-Claisen rearrangement sequence applied to readily available propargyl glycolates was developed as a route toward functionalized alkylidene(gem-difluorocyclopropanes). This strategy conveniently avoids the isolation of the unstable 3,3-difluorocyclopropenylcarbinyl glycolates arising from the difluorocyclopropenation. The Ireland-Claisen rearrangement proceeds with high diastereoselectivity and chirality transfer to afford alkylidene(gem-difluorocyclopropanes) incorporating a quaternary stereocenter and a protected glycolic acid moiety, which are useful building blocks for the preparation of functionalized gem-difluorocyclopropanes.

[3,3]‐Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives

“…Although the [3,3]-sigmatropicr earrangement of allylic cyanates is concerted and proceeds with ah igh level of chirality transfer,ahighly asynchronous process is involved in which dissociation of the allylic carbon-oxygen bond is more advanced in the transition state than formation of the carbon-nitrogen bond. [35] Due to the peculiar structure and bonding properties of the cyclopropene ring, [37] cyclopropenylcarbinols should rather be compared to propargylic rather than to allylic alcohols and it was of interest to check whether the [3,3]-sigmatropic rearrangement of cyclopropenylcarbinyl cyanates would proceed with chirality transfer.C arbamate (R)-3a (ee = 88 %), prepared from the optically enrichedcyclopropenylcarbinol (R)-1a, [28,38] wase ngaged in the sequence devised previously (TFAA/Et 3 N, CH 2 Cl 2 , À78 8C, 1h,t hen morpholine, À78 8C to RT) and the optically enriched urea( À)-6 possessing an enantiomeric excess of 86 %w as isolated (75 %). [39] Thisl atter result demonstrates that ah igh level of chirality transfer can be achieved in the allylic transposition of cyanate 4a (Scheme 4).…”

“…[25] Sigmatropicr earrangements involvingc yclopropenylcarbinol derivatives constitute an interesting entry to diversely substituted alkylidene cyclopropanes. [26][27][28] In 2013, Hyland and coworkers reportedt hat the [3,3]-sigmatropic rearrangemento f trichloroacetimidates F,d erived from (2-methylcyclopropenyl)carbinols E,p rovided as tereoselective access to alkylidene [N-(trichloroacetyl)aminocyclopropanes] G possessing an exocyclic olefin of E configuration (Scheme 2). [29] Although this so-called Overmanr earrangement of trichloroacetimidates F proceeds under mild conditions owing to the relief of ring-strain, the scope is restricted to substrates E substituted by an electronrich or -neutral (hetero)aromatic group.…”

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

“…The Ireland–Claisen rearrangement was then extended to a challenging class of cyclopropylcarbinyl glycolates possessing gem -difluoro substitution at C3 [65]. Gem -difluorocyclopropenes are accessible by difluorocyclopropenation of alkynes with difluorocarbene but these compounds display poor stability in most cases and readily undergo hydrolysis into cyclopropenones which possess an aromatic character [66–67].…”

A Solid Iridium Catalyst for Diastereoselective Hydrogenation

“…This orientation was the result of formation of a stable chelating complex of Ir center with the hydroxyl group and the double bond of the substrate. The ability of Crabtree′s catalyst to transfer hydrogen stereoselectively was successfully utilized in total synthesis of natural products . It is worth mentioning that in some cases the use of Crabtree′s catalyst was the only possible way to reach targeted molecules …”

“…The ability of Crabtree'sc atalyst to transfer hydrogen stereoselectively was successfully utilized in total synthesis of naturalp roducts. [4][5][6][7][8][9][10][11] It is worth mentioning that in some cases the use of Crabtree'sc atalyst was the only possible way to reach targeted molecules. [12][13][14] In sharp contrast, the terpinen-4-ol hydrogenation performed underh eterogeneous catalysis led to selectivities ranging from 20 to 53 %d epending on the solvent polarity.…”