Rhodium-Catalyzed Intermolecular C–H Functionalization as a Key Step in the Synthesis of Complex Stereodefined β-Arylpyrrolidines

Abstract

The synthesis of β-arylpyrrolidines via a catalytic enantioselective intermolecular allylic C(sp)-H functionalization of trans-alkenes followed by immediate reduction, ozonolysis, and then in situ diversification of the resulting cyclic hemiaminal to furnish highly substituted, stereoenriched β-arylpyrrolidines is reported. This methodology utilizes 4-aryl-1-sulfonyl-1,2,3-triazoles as carbene precursors and the dirhodium tetracarboxylate catalyst Rh( S-NTTL). A variety of β-arylpyrrolidines were prepared in good yields with high levels of diastereo- and enantioselectivity over four linear steps, requiring only a single purification procedure.

Distal Allylic/Benzylic C−H Functionalization of Silyl Ethers Using Donor/Acceptor Rhodium(II) Carbenes

“…The reaction can be extended to other aryl‐substituted triazoles as illustrated in the formation of the distal C−H insertion products ( 12 g – 12 i ) with moderate yields and excellent levels of diastereo‐ and enantioselectivitiy (>20:1 d.r., 93–98 % ee ). The relative configuration of these compounds can be readily assigned on the basis of shielding effects arising from preferred conformers of the products and literature precedents . In the case of 12 d , both the relative and absolute configurations were unambiguously determined from the X‐ray structure of its desilylated derivative.…”

Recent Advances in the Synthesis of 5‐MemberedN‐Heterocycles via Rhodium Catalysed Cascade Reactions

“…The key step is allylic CÀ H functionalization with 4-phenyl-N-methanesulfonyl-1,2,3-triazole 21 as a donor/acceptor carbene precursor to access a wide variety of β-aryl pyrrolidines in good yields with high levels of diastereo-and enantioselectivity (Scheme 5). [16] Indole skeletons are decisive and copiously found in natural products and drug molecules. [17a-c] Specifically 2-arylindoles are regarded as significant core units of various biological active compounds including tubulin polymerization inhibitors and strong antiplasmodial activity (isocryptolepine), and antiviral hepatitis C virus (HCV) inhibitors.…”

“…The key step is allylic C−H functionalization with 4‐phenyl‐ N ‐methanesulfonyl‐1,2,3‐triazole 21 as a donor/acceptor carbene precursor to access a wide variety of β ‐aryl pyrrolidines in good yields with high levels of diastereo‐ and enantioselectivity (Scheme 5). [16] …”

Catalytic Insertion Reactions of α‐Imino Carbenoids

“…In the same year, Davis and co-workers demonstrated another interesting methodology to generate stereoenriched βaryl pyrrolidines 23 from 4-aryl-1-sulfonyl-1,2,3-triazoles 9 and trans-alkenes 19 (Scheme 6). [18] The sequential reaction involved Rh 2 (S-NTTL) 4 C7 catalyzed enantioselective intermolecular allylic C(sp 3 )À H functionalization of alkenes with RhÀ AVC to generate the imine 20 and subsequent LiAlH 4 reduction to amine 21, ozonolysis of alkene functionality resulted in intramolecular cyclization to hemiaminal 22, which on in situ reduction with triethylsilane gave access to highly substituted β-aryl pyrrolidines 23.…”