Polymer‐supported chiral diol as ligand of Ti(IV) for enantioselective Diels‐Alder reaction

Abstract

The synthesis of the first polymer-supported TADDOL is reported. Its efficiency as chiral ligand of Ti(IV) was studied in the Diels-Alder cycloaddition of cyclopentadiene to 3-crotonoyl-1,3-oxazolidin-2-one, and was superior to that observed for its homogeneous equivalent, (4R,5R)-␣,␣,␣Ј,␣Ј-2-pentaphenyl-4,5-dimethanol-1,3-dioxolane. Recycling of the heterogeneous Ti(IV)-TADDOLate was also studied, being the most suitable method for the repreparation of the catalyst from the ligand after use. Chirality 9:191-197, 1997. © 1997 KEY WORDS: TADDOL; titanium complexes; chiral Lewis acid; polymer-supported; polystyrene-divinylbenzene; enantioselective; Diels-AlderThe Diels-Alder reaction is probably the most important synthetic method for obtaining cyclohexenes and is the key step in the synthesis of a large number of natural products.1 in the last few years, the asymmetric Diels-Alder reaction using chiral catalysts has been widely studied. [2][3][4] Especially interesting are the chiral Ti(IV) reagents derived from an achiral Ti(IV) Lewis acid and a 1,4-diol of general structure ␣,␣,␣Ј,␣Ј-tetraaryl-1,3-dioxolane-4,5-dimethanol 4,5 (TADDOL, Fig. 1). This family of compounds has proved to be an effective chiral catalyst not only in Diels-Alder reactions 6-8 but also in other types of reactions such as nucleophile addition to aldehydes, 4,9 enereaction, 10,11 [2+2] cycloadditions, 12 1,3-dipolar cycloaddition, 13 and hydrocyanation of aldehydes. 14 Very recently Greeves and co-workers 15 have reported the use of TADDOLs as chiral ligands for enantioselective addition of organocerium regents to aldehydes.Since the pioneering work of Merrifield 16 in solid-phase synthesis, much effort has been made in the development of new applications. Recently, attention has been focused in polymer-supported chiral catalysts because of the advantages implied: ease of chiral auxiliary isolation, ease of recovery and applicability in flow systems.Several polymeric chiral Lewis acids have been developed for asymmetric alkylations, [17][18][19] reductions, 20 or epoxidations, 21 but to our knowledge only Itsuno and coworkers 22 have synthesized effective polymeric chiral catalysts for enantioselective Diels-Alder reactions. These authors have studied the efficiency of several Nsulfonylamino acids, amino-alcohols, and diols anchored to an insoluble support as ligands of boron in the cycloaddition of cyclopentadiene to methacrolein, being 65% enantiomeric excesses (e.e.) 22a the best optical yield reached for the exo cycloadduct.Following our previous work on the enantioselective Diels-Alder reaction, 8 we report the synthesis of the polymer-supported TADDOL 1 (P-TADDOL, heterogeneous equivalent of (4R,5R)-␣,␣,␣Ј,␣Ј-2-pentaphenyl-4,5-dimethanol-1,3-dioxolane (2) (Fig. 2)), and its efficiency as a chiral ligand of Ti(IV) in the Diels-Alder addition of cyclopentadiene to 3-crotonoyl-1,3-oxazolidin-2-one. MATERIALS AND METHODS1 H-NMR spectra were recorded on a Varian-Gemini 300 spectrometer (Palo Alto, CA) at 300 MHz, in CDCl 3 , and ...

TADDOLs, Their Derivatives, and TADDOL Analogues: Versatile Chiral Auxiliaries

“…As both hexaphenyl-TADDOL 1 g and the cyclohexane derivative readily form titanium complexes-which, for example, catalyze nucleophilic addition to aldehydes [112] as well as Diels-Alder reactions [113] in the usual way-one must conclude that both diolates function as chelate ligands, and that in this case a rule of thumb that is familiar to inorganic and complex chemists applies: it is not possible to predict the structure of a ligand in a metal complex from that of the ligand alone.…”

“…[379] This is a condition fulfilled by the titanium TADDOLate catalyzed addition of R 2 Zn to aldehydes [380] (Scheme 12) and the [32] cycloaddition of nitrones, [71] but not by the Diels ± Alder reaction of enoyloxazolidinones. [71,113,381] Finally, ease of utilization requires that the particles of an immobilized catalyst not be too small, for which reason our conditions for suspension polymerization have been so adjusted that spheres with a diameter of approximately 400 mm are preferentially formed. These can easily be confined, but they are also readily removed from a reaction solution simply by filtering or decanting, or by removing the supernatant solution with fine needles (Figure 15).…”

TADDOL and Its Derivatives – Our Dream of Universal Chiral Auxiliaries

“…TADDOL Precursors for Grafting (on Merrifield resin or on controlled-pore glass) and for Cross-Linking Suspension Copolymerization with Styrene. These TADDOL derivatives are prepared in the usual way from (suitably protected) components [21] [78][79][80][81]. The zero-and first-generation Fréchet-type [82] branches were attached by reaction of branch benzyl bromides with a TADDOL bearing four phenolic OH groups [22][78] [79].…”

TADDOLe, ihre Derivate und Analoga – vielseitige chirale Hilfsstoffe

“…Aus der Tatsache, dass sowohl das Hexaphenyl-TADDOL 1 g als auch das Cyclohexanderivat problemlos einen Ti-Komplex bilden, der z. B. nucleophile Additionen an Aldehyde [112] oder auch Diels-Alder-Reaktionen [113] in gewohnter Weise katalysiert, muss man schlieen, dass beide Diolate Chelatliganden sind und dass in diesem Fall die unter Anorganikern und Komplexchemikern gebr‰uchliche Faustregel gilt, nach der man von der Struktur eines Liganden nicht auf die seiner Metallkomplexe schlie˚en darf.…”

“…Chem. 2001, 113, 96 ± 142 hinzuweisen, dass nur solche Anwendungen infrage kommen, bei denen in homogener Lˆsung kein nichtlinearer Effekt (NLE) auftritt, der darauf beruht, dass mehr als ein Katalysatormolek¸l am geschwindigkeitsbestimmenden Schritt beteiligt ist, [379] eine Bedingung, die f¸r die Ti-TADDOLatkatalysierte R 2 Zn-Addition an Aldehyde [380] (Schema 12) und f¸r die [32]-Cycloaddition von Nitronen, [71] nicht aber f¸r die Diels-Alder-Reaktion von Enoyloxazolidinonen [71,113] erf¸llt ist. [381] Schlie˚lich gebietet die einfache Handhabung der immobilisierten Katalysatoren, dass die Partikel nicht zu klein sind, weshalb wir die Bedingungen bei der Suspensionspolymerisation so einrichteten, dass bevorzugt K¸gelchen von ca.…”