Organocatalyzed Assembly of Chlorinated Quaternary Stereogenic Centers

Abstract

Abstract:The catalytic asymmetric construction of chiral quaternary stereocenters is always a continuous area of research in organic chemistry. In this sense, when a chlorine atom takes part in a quaternary stereocenter, the difficulty of its synthesis increases along with the significance of the resulting products. This is true, not only because of the intrinsic interest of such chlorinated molecules, but also because they are considered as highly valuable chiral building blocks in organic synthesis, as they can be converted to more complexes molecules by a simple S N 2 displacement. Among the different strategies followed to create chlorinated quaternary stereogenic centers, organocatalysis has played a pivotal role during the last decade. In this review, a comprehensive analysis of such organocatalyzed transformations, which are mainly focalized on the the -chlorination of carbonyl compounds, is presented.

C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

“…[22] Under these conditions (THF, 15 8C, 40 hours) a series of novel chlorinated coumarin derivatives 6 a-6 g were obtained as major products with isolated yields between 51 to 74%. [20] In conclusion, we have highlighted the reactivity of C5-disubstituted Meldrum's acid derivatives as novel platforms for the enantioselective organocatalytic synthesis of medicinally relevant 3-alkylated dihydrocoumarins in up to 93:7 er, thanks to a domino cylizationdecarboxylative protonation reaction trigerred by a novel cuprein organocatalyst. Worthy of note, it was proven that the catalytic chlorination reaction did not occur on the coumarin product 2 a.…”

“…Furthermore, this approach allows the elaboration of unprecedented a,a-disubstituted coumarins [3] with a versatile tertiary chlorinated stereocenter. [20] In conclusion, we have highlighted the reactivity of C5-disubstituted Meldrum's acid derivatives as novel platforms for the enantioselective organocatalytic synthesis of medicinally relevant 3-alkylated dihydrocoumarins in up to 93:7 er, thanks to a domino cylizationdecarboxylative protonation reaction trigerred by a novel cuprein organocatalyst. The versatility of these platforms was demonstrated through an original (second report to date) enantioselective decarboxylative chlorination reaction towards the construction of chroman-2-ones with a tertiary chlorinated stereocenter with up to 79:21 er.…”

“…At the onset, we considered the beautiful and unprecedented enantioselective decarboxylative chlorination reaction recently reported by Shibatomi et al [13], [20] This strategy applied to our domino cyclization-decarboxylative process would provide an unprecedented entry to dihydrocouramins 6 having a C3chlorinated tetrasubstituted stereocenter (Scheme 7). At the onset, we considered the beautiful and unprecedented enantioselective decarboxylative chlorination reaction recently reported by Shibatomi et al [13], [20] This strategy applied to our domino cyclization-decarboxylative process would provide an unprecedented entry to dihydrocouramins 6 having a C3chlorinated tetrasubstituted stereocenter (Scheme 7).…”

“…Next, we wondered whether it could be possible to take advantage of the reactivity of the readily available Meldrum's acid platforms 4, for the construction of more substituted dihydrocoumarin derivatives. At the onset, we considered the beautiful and unprecedented enantioselective decarboxylative chlorination reaction recently reported by Shibatomi et al [13], [20] This strategy applied to our domino cyclization-decarboxylative process would provide an unprecedented entry to dihydrocouramins 6 having a C3chlorinated tetrasubstituted stereocenter (Scheme 7).…”

Asymmetric Organocatalytic Electrophilic Heterofunctionalization of Oxindoles

“…The organocatalytic asymmetric chlorination of oxindoles is an uncommon reaction, [28] and there are very few examples that employ Brønsted bases as organocatalysts. The enantioselective C3 chlorination of 3-aryloxindoles with cinchona alkaloid derivative 11 as the organocatalyst and N-chlorosuccinimide (NCS) as the chlorine source is one example (Scheme 11).…”