Enantioselective Cycloaddition Reactions Catalyzed by BINOL-Derived Phosphoric Acids and N-Triflyl Phosphoramides: Recent Advances

Abstract

Over the last several years there has been a huge increase in the development and applications of new efficient organocatalysts for enantioselective pericyclic reactions, which represent one of the most powerful types of organic transformations. Among these processes are cycloaddition reactions (e.g., [3+2]; formal [3+3]; [4+2]; vinylogous [4+2] and 1,3-dipolar cycloadditions), which belong to the most utilized reactions in organic synthesis of complex nitrogen-and oxygen-containing heterocyclic molecules. This review presents the breakthrough realized in this field using chiral BINOL-derived phosphoric acids and N-triflyl phosphoramide organocatalysts.

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

“…A class of powerful organocatalysts is represented by Brønsted acid catalysts such as BINOL-derived phosphoric acids, which have already been applied in numerous highly enantioselective transformations [40][41][42][43][44][45][46][47][48][49] since the pioneering studies by the groups of Akiyama et al [50] and Uraguchi and Terada [51].…”

Enantioselective Oxidative (4+3) Cycloadditions between Allenamides and Furans through Bifunctional Hydrogen‐Bonding/Ion‐Pairing Interactions

“…[5] In most cases, heteroatom-stabilized oxyallyl cations [6] have been used as dienophiles,and almost all processes focused on diastereoselective approaches that relied on the use of inherently chiral substrates [7] or chiral auxiliaries. In particular,asmentioned, there is no precedent for areaction in which b-substituted oxyallyl cations are used as dipoles in this transformation, which therefore limits this method to cycloheptanone adducts without any substituents at the a'-position with respect to the ketone moiety.In this sense,w eh erein report that chiral BINOL-based Brønsted acids [11] catalyze the (4+ +3) cycloaddition [12] between differently substituted furans and oxyallyl cations that are generated in situ by oxidation of allenamides (Scheme 1). [10] In addition, both methods required al arge excess (5-13 equiv) of the diene to provide synthetically useful yields and can only be employed with oxyallyl cations without any substituents at the terminal position.…”

“…Only aslight improvement in enantioselectivity was observed with the more acidic N-trifluoromethanesulfonyl phosphoramide catalyst 3e (entry 6). [17] Remarkably,y ield ande nantioselectivityc ould be furtheri mprovedbyc hanging thesolvent to EtOAc(entry15),and with othersolvents,better resultsw eren ot observed (entries [12][13][14][15].M oreover, the reaction canb ec arried outw ithf uran as thel imitingr eagent (entry 16). Theseexperiments indicatedthatadonor/acceptor pattern washighlybeneficialf or they ield ands tereoselectivityo ft he reaction,and cycloadduct 4fwasobtainedinavery promising yieldof63% and85:15 e.r.…”

“…In this sense,w eh erein report that chiral BINOL-based Brønsted acids [11] catalyze the (4+ +3) cycloaddition [12] between differently substituted furans and oxyallyl cations that are generated in situ by oxidation of allenamides (Scheme 1). We relied on the hypothesis that such chiral Brønsted acids would favor the formation of the oxyallyl cation intermediate through ring opening of the alkylideneoxirane intermediate that is generated upon chemoselective epoxidation of the allenamide and would also remain attached to this oxyallyl cation through an unconventional bifunctional mode of activation that combines hydrogen-bonding and ion-pairing interactions, [13] thereby exerting their stereochemical influence during the (4+ +3) cycloaddition process.…”

“…when theNatom of theallenamide wassimultaneouslysubstituted with a tert-butoxycarbonyland a para-methoxyphenyl group( entry11). [17] Remarkably,y ield ande nantioselectivityc ould be furtheri mprovedbyc hanging thesolvent to EtOAc(entry15),and with othersolvents,better resultsw eren ot observed (entries [12][13][14][15].M oreover, the reaction canb ec arried outw ithf uran as thel imitingr eagent (entry 16). [18] With theseoptimized conditions in hand,wealso surveyed aw idefamilyofother chiral N-trifluoromethanesulfonylp hosphoramide catalystsb ut withouto bserving any improvements in termsofthe performanceofthe test reaction (see theS upportingI nformation ford etails).I na ll of these experiments, thec ycloadducts 4a-4f were isolated as single diastereomers.…”