Oxonium Ylide Rearrangement of Enzymatically Desymmetrized Glutarates

Abstract

The combination of an enzyme-mediated enantioselective desymmetrization of readily available 3-benzyloxyglutarates and subsequent rhodium-catalyzed oxonium ylide rearrangement of their corresponding in situ derived diazo ketones offers a very concise and highly stereoselective access to functionalized tetrahydrofuranone building blocks.

Kirmse–Doyle‐ and Stevens‐Type Rearrangements of Glutarate‐Derived Oxonium Ylides

“…Under similar conditions (butynyl trichloroacetimidate, TMSOTf, DCM, RT), propargylation yielded 2 k in 60 % . As already disclosed in our previous communication, benzylic ethers were accessible via a Lewis acid‐mediated, reductive etherification to give rise to 2 e–2 j in moderate to good yields (46–82 %). Finally, two alkoxymethyl ethers were synthesized by treatment of alcohol 1 with the respective alkoxymethyl chlorides and Hünig's base ( 2 l , 60 %; 2 m , 64 %).…”

“…The major isomer 6 was crystallized and X‐ray crystal structure analysis unambiguously confirmed the anticipated connectivity and relative stereochemistry resulting from the previous oxonium ylide rearrangement step (see Supporting Information for ORTEP and crystallographic data). The thus obtained alcohols can on one side be used as functional building blocks towards more complex heterocyclic targets, but could also act as precursors for 2,5‐disubstituted tetrahydrofurans through Barton–McCombie deoxygenation …”

“…Herein, we provide a detailed account on of our efforts to develop this chemoenzymatic approach utilizing various functionalized symmetric glutarates. On the basis of our prelimnary results focusing on benzyl shift rearrangements, this report puts emphasis on the synthetically even more appealing [2,3]‐sigmatropic oxonium ylide chemistry for the synthesis of alkene and allene‐substituted tetrahydrofurans and its application in streamlined strategies towards complex heterocyclic building blocks with full control over multiple stereogenic centers.…”

Recent Advances in Asymmetric [1,2]-Stevens-Type Rearrangement via Metal Carbenes

“…However, the yields and diastereoselectivities of desired tetrahydrofuranone products were relatively low (Scheme 5 ). 22 Moreover, after systematic evaluation of catalysts, the authors found the transformation to be catalyst-dependent. In different catalytic systems, the [1,2]- and [2,3]-rearrangements could be achieved selectively with [Cu(MeCN) 4 ]PF 6 or Rh 2 (oct) 4 as catalyst.…”

Hot off the press

“…Prochiral 3-benzyloxyglutarates have been subjected to a Candida antarctica lipase B (CALB) mediated desymmetrisation (Scheme 9). 30 Conversion of the resulting carboxylic acid into a diazo ketone and rhodium catalysed oxonium ylide rearrangement allowed access to functionalised tetrahydrofuranone building blocks.…”