Kinetic Enzymatic Resolution of Cyclopropane Derivatives

Abstract

Abstract:The kinetic enzymatic resolution of various cyclopropane derivatives was systematically investigated. The study focused on synthetically useful cyclopropylmethanols (e.g., 18a/j or 19a/j) as well as some rarely investigated cyclopropanols (e.g., 24/25 or 27). The combination of enantioselective catalytic or diastereoselective synthesis of enantiomerically enriched compounds with enzymatic approaches ultimately led to the most convenient route to enantiomerically pure starting materials. Again, this was especially proven for the synthesis of cyclopropanols 18a/j and 19a/j. Key to the successful investigation was to rigorously establish an analytical tool for the analysis of enantiomeric composition of reaction mixtures.

Total Synthesis of Marine Oxylipins Solandelactones A–H

“…Next we focused on the synthesis of cyclopropyl lactone 11 (Scheme 2). The enantiomerically pure cyclopropane 15 -whose synthesis was previously described via a reliable chemoenzymatic route (58% yield over 5 steps from cinnamyl alcohol) [9] -was the starting material of choice. After deprotection (96%), oxidation with Dess-Martin periodinane [10] (91%) and allyl addition with Leightons reagent 16 [11] furnished homoallylic alcohol 17 (95%; dr 95:5).…”

General and Efficient α‐Oxygenation of Carbonyl Compounds by TEMPO Induced by Single‐Electron‐Transfer Oxidation of Their Enolates

“…Therefore the significantly more sensitive 2‐phenylcyclopropane probes 22 and 23 were used in the oxygenation reactions (Scheme ) 29. They were synthesized in a straightforward manner by a Simmons–Smith cyclopropanation of cinnamic alcohol ( 20 ),30 followed by the bromination of 21 31. Kolbe nitrile synthesis furnished 22 ,32 which was transformed by hydrolysis and alkylation into (2‐phenylcyclopropyl)acetate 23 in good overall yield.…”

Enantiomerically Pure Vinylcyclopropylboronic Esters

“…was used. In view of the present vinylcyclopropane study we were especially pleased to find that substrates 23l,b [28,29] do not represent any problem: the products 10l,b were obtained in 65 and 62 % yields, respectively. The protected boron moiety of the products remained intact and could be further elaborated in consecutive steps (see below).…”

“…On the other hand, a heterocyclic substituent, as in the thiophene derivative 23j, represents no problem (yield of cyclopropane 10j: 79 %). Even cyclopropane/cyclopropane coupling was achieved in good yield (67 % of dicyclopropane 10k); instead of using the boronic acid, the corresponding dioxaborinane 23k [28] was used. In all cases the boron derivative 23 was added in access (1.5 equiv.)…”

“…Iodocyclopropane 22a (80 mg, 0.13 mmol, 1 equiv. ), the rac-phenylcyclopropylboronic ester 23k [28] (0.04 g, 0.19 mmol, 1.5 equiv. ), the catalyst [Pd(PPh 3 ) 4 ] (12 g, 0.01 mmol, 0.07 equiv.)…”