Stereodivergent Synthesis of Enantioenriched 4-Hydroxy-2-cyclopentenones

Abstract

Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of intermediates in chemical synthesis. A route to this class of compound has been developed. Key steps include Noyori reduction (which establishes the stereochemistry of the product), ring-closing metathesis, and simple functional group conversions to provide a set of substituted 4-HCPs in either enantiomeric form.

Synthesis of cyclic 1,3-diols as scaffolds for spatially directed libraries

“…The four stereoisomers of mono-TIPS protected cyclopentanediol 3 were prepared from 2 8 by the straightforward modification of our previously published route to 4-silyloxy-cyclopenten-2-ones (Scheme 1a). 9 The diols were prepared and used as TIPS derivatives to ensure stepwise substitution of the cyclopentenediols by diversifying groups. The conversion of trans -(S,S)- 3 to the corresponding cis isomer was accomplished by a Mitsunobu reaction, which generates an interesting molecule that is chiral solely by virtue of the placement of a protecting group on what would otherwise be a meso diol.…”

“…Having previously encountered unexpected difficulties in monosilylation of symmetrical diols, 9 this was viewed as an attractive entry into these monoprotected building blocks for library synthesis. As demanded by parity conservation, application of these reaction sequence beginning with ( S , S )- 1 led to the enantiomers of these building blocks (not shown).…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…224) [575], transpentacin derivatives [576], bis spirocyclopentenes [577], nardoaristolone B and analogs [578], cyclaradine [579], carbocyclic nucleoside analogs [580], cyclopentenefused nucleosides [581], cyclopentenols for the preparation of enantio enriched 4-hydroxy-2-cyclopentenones [582], and failure to form a five-membered ring bridge of a nucleoside derivative by RCM [583]; (2) cyclopentenes and dihydrofurans [584]; (3) α,β-unsaturated cyclopentenones [585], including those employed in syntheses of TEI-9826 [586]; (4) five-and six-membered ring alkenes substituted by electron-withdrawing groups [587]; (5) five-and six-membered rings fused (spiro or regular fusion) to indole systems [588]; (6) fiveand six-membered rings spiro fused to a 1,2-diphenylpyrazolidine-3,5-dione ring system [589]; (7) five-to seven-membered ring carbocycles and oxygen heterocycles using biocatalytically-derived starting materials [590]; (8) five-to seven-membered ring carbocycles [591]; (9) five-to seven-membered ring carbocyclic and heterocyclic vinylboronates (e.g. 225) [592]; (10) cyclohexenes, including those employed in syntheses of fluorinated inositol analogs [593], fluorinated cyclohexenes [594], lundurine B (the enol ether was converted to the ketone without isolation) (e.g.…”

Chemoenzymatic Synthesis towards the Active Agent Travoprost

“…Tremendous effort has been invested in the enantiomerically pure synthesis of 4‐hydroxy‐2‐cyclopentenones and their O ‐silyl‐derivatives, such as building block A , owing to it being a valuable synthetic intermediate for the synthesis of prostaglandins . These building blocks also function as cornerstones in the synthesis of numerous other natural compounds, including alkaloids, terpenes, and many more …”

“…[6, 14b, 19-21] These building blocks also functiona sc ornerstones in the synthesis of numerouso ther natural compounds, includinga lkaloids, [22][23][24][25] terpenes, [26,27] and many more. [28][29][30][31] Althought here are several approaches for the preparation of A,m ost of them are based on the meso-diol 4 or the diacylated molecule 5.I na ni nitial investigation, we started our endeavor towards (R)-4-hydroxyketone 6 by using these commercially available materials that can also be readily prepared by established methodsf rom cyclopentadiene. [32] The first step in our syntheticr oute to A was al ipase-catalyzed desymmetrization startingf rom either meso-diol 4 or the diacetylated compound 5 (Scheme 2).…”