Asymmetric annulation

See D. Rajagopal, R. Narayanan, S. Swaminathan, Tetrahedron Letters 2001, 42, 4887 for a one-pot asymmetric annulation procedure. 

Keywords 2-formylcycloalkanone, methyl vinyl ketone, proline, Robinson annu-lation, asymmetric annulation, spiro compound... 

A palladium-catalyzed asymmetric annulation of the allene 1133 with 2-iodobenzoic acids proceeds in the presence of a chiral bisoxazoline ligand to afford 4-methylenedihydroisocoumarins in good yield and enantiomeric excess (Equation 440) <1999JOC7312>. 

A novel Pd-catalyzed asymmetric annulation was reported between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines <07OL2357>. The resulting pyrrolopiperazinones such as 58 served as key intermediates in the enantioselective synthesis of longamide B and a number of other pyrrole alkaloids. 

Studies on asymmetric annulation of the precursor 203 resulted in development of reaction conditions for the construction of the fused indoline system 204 (Equation 64). Similar cyclization of a substrate containing a longer chain gave a corresponding indoline fused to a six-membered ring <2002TA1351>. 

Scheme 5.11 Pd-catalyzed asymmetric annulation of ferrocene derivatives with diarylethynes reported by You.

In 2006, the Bode group documented NHC-catalyzed highly enantiose-lective 1-oxodiene Diels-Alder reactions of a broad range of enones with racemic a-chloroaldehydes as the dienophile precursors. This process affords a diverse set of highly enantioenriched 3,4,6-trisubstituted dihydro-pyran-2-ones from readily available starting materials under mild conditions (room temperature, 1.5 equiv. of NEtj, 6 h). The use of readily accessible racemic a-chloroaldehydes as enolate precursors greatly expands the scope of enantioselective NHC-catalyzed Diels-Alder reactions. It also makes possible, for the first time, asymmetric annulations with exceptional enantiose-lectivity under reliable eonditions with less than 1 mol% of a chiral NHC catalyst (Scheme 7.77). 

Scheme 7.96 NHC-catal)rzed asymmetric annulation reaction of ynals and enols reported by Bode.

Scheme 7.102 NHC-catalyzed asymmetric annulation of 2-bromoenals with indo-lin-3-ones reported by Enders.

Scheme 7.103 NHC-catal3 ed asymmetric annulation of 2-bromoenals with heterocyclic C—H acids reported by Biju.

Scheme 7.108 NHC-catalyzed oxidative asymmetric annulation of enals with 1,3-dicarbonyls reported by You.

Under the dual catalysis of AgOAc and a chiral phosphoric acid, asymmetric annulation of 3-alkynylacrylaldehydes with 2-hydroxystyrenes affords complex multiring-fused chromans (14JOC7063). A variety of... 

NHC-catalysed umpolung of enals appears to be a useful tool for annulation reactions that generally induces molecular complexity from simple starting materials. Enals have thus been reported as appropriate reaction partners for asymmetric annulation reactions with isatins and benzodi(enone)s to yield spirocyclic oxindolo-y-butyrolactones (121), and polycyclic compounds (122), respectively. Both annulation processes have been catalysed by chiral NHCs and accomplished in good yields with high regio- and/or stereo-selectivities. In parallel, the mechanism of the NHC-catalysed annulation reaction of butenal with pentenone has been computationally explored at the B3LYP/6-31+G and M06-2X/6-31G levels of theory. This study has clearly emphasized the key role played by proton-transfer steps in both the rate and the course of the reaction. 

Recently, 13 was reported to catalyze the asymmetric annulation reaction between allenoates and a,P-unsaturated carbonyl compounds to form substituted 2H-pyrans (Scheme 6.15) [37]. This formal [4+2] cycloaddition afforded exclusively the product with the (E) configuration of the exocyclic double bond, in line with calculations that indicated the ( )-isomer to be about 14.2 kj mol lower in energy than the (Z) isomer. The mechanism of the reaction was formulated as an initial attack by the nitrogen atom of the quinuclidine ring at the allenoate with formation of an ionic intermediate that preferentially reacts at the terminal carbon atom with the a,p-unsaturated carbonyl compound prior to elimination of the catalyst with formation of the 2H-pyran derivative (Scheme 6.15). 

Scheme 6.15 Asymmetric annulation reaction catalyzed by 13 (NR3 in the scheme).

Scheme 20.27 Spiro-phosphine-catalyzed asymmetric annulation reactions.

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