Nonracemic γ‐Lactones from the Sharpless Asymmetric Dihydroxylation of β,γ‐Unsaturated Carboxylic Esters

Abstract

Since Sharpless' discovery of the asymmetric dihydroxylation of C=C double bonds in the late 1980s this reaction has become a powerful tool of synthetic organic chemistry. As a consequence, this transformation has been reviewed repeatedly and extensively. The present microreview focuses on Sharpless' asymmetric dihydroxylations (from here on “SADs”) of β,γ‐unsaturated carboxylic esters. These SADs differ from most others in that they provide not nonracemic 1,2‐diols but follow‐up products thereof. Bearing ester groups at appropriate distances, the SAD‐based 1,2‐diols obtained from β,γ‐unsaturated carboxylic esters lactonize readily under SAD conditions. Accordingly, SADs of β,γ‐unsaturated carboxylic esters furnish nonracemic β‐hydroxy‐γ‐lactones in a single operation. We show that this SAD route represents a – or even the most – potent easy‐to‐handle route to nonracemic butanolides and butenolides “of almost all kinds”. The span covered is from pioneering racemic work to applications in natural product synthesis. Some non‐butanolide and non‐butenolide target syntheses are included, especially those of tetrahydrofurans.

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

“…[5b,38] Accordingly, 11 should be reached analogously,that is,byadihydropyranforming oxa-Pictet-Spengler cyclization [39] of b-hydroxy-glactone 12,w hich itself should result from an asymmetric dihydroxylation of the trans-configured b,g-unsaturated ester 15. [40] Such esters can be obtained by the Heck coupling of an aryl halide and an alkyl 2-vinylacetate. [41] We intended to use naphthalene dihalides 14 as substrates.T hey should result from halogenations of tetramethoxynaphthalene 13.…”

Controlling the Substitution Pattern of Hexasubstituted Naphthalenes by Aryne/Siloxyfuran Diels–Alder Additions: Regio‐ and Stereocontrolled Synthesis of Arizonin C1 Analogs

“…Each arizonin C1 analog of Figure or Scheme was prepared by an identical series of 4 late steps: 1) Heck‐coupling; 2) asymmetric dihydroxylation; 3) oxa‐Pictet–Spengler reaction; oxidation of the naphthohydroquinone (details: below). This strategy equals one, which we followed in total syntheses of the naphthoquinonopyrano‐γ‐lactone natural products (+)‐kalafungin ( 1a ),[7c] (–)‐arizonin B1 ( 2 ),[7r] (–)‐arizonin C1 ( 3 ),[7s] and (+)‐γ‐actinorhodin , .…”

“…Using (DHQ) 2 PHAL or (DHQD) 2 PHAL as a chiral auxiliary we obtained the β‐hydroxy‐γ‐lactone 15 with 98.5 % ee and its antipode ent ‐ 15 with 96 % ee , respectively. The β,γ‐dihydroxyesters, formed initially, transesterified under the dihydroxylation conditions giving lactones although they implied less base‐catalysis than usually . Next, the lactones 15 and ent ‐ 15 were diversified in a total of nine oxa‐Pictet–Spengler cyclizations .…”

Die erste stereoselektive Totalsynthese eines dimeren γ‐Lacton‐ anellierten Pyranonaphthochinons: (+)‐γ‐Actinorhodin

“…Diese Verbindung ist mit halogenfreien γ‐Lacton‐anellierten Pyranonaphthochinonen strukturverwandt, die wir bereits herstellten . Daher planten wir einen analogen Zugang zu 11 : per Oxa‐Pictet‐Spengler‐Cyclisierung des β‐Hydroxy‐γ‐lactons 12 , das durch eine asymmetrische Dihydroxylierung des trans ‐konfigurierten β,γ‐ungesättigten Esters 15 zugänglich sein sollte . Solche Ester gewinnt man durch Heck‐Kupplung eines Arylhalogenids mit einem But‐3‐ensäureester .…”