Pd(ii)-catalyzed alkoxylation of unactivated C(sp3)–H and C(sp2)–H bonds using a removable directing group: efficient synthesis of alkyl ethers

Abstract

The Pd(II)-catalyzed alkoxylation of unactivated C(sp 3 )-H and C(sp 2 )-H bonds using a new bidentate directing group has been developed. Alkoxylation occurs selectively at the b position with broad substrate scope and high tolerance of functional groups (chloro, cyano, ether, ester, olefin, amino, etc.). Besides alkoxylation of the b-C-H bonds, g-alkoxylation of C(sp 2 )-H bonds could also be achieved, provided that no reactive b-C-H bonds were present. In addition, this DG is readily available and removable.Scheme 1 Pd-catalyzed direct alkoxylation of C-H bonds.

Stereoselective Synthesis of Chiral α‐Amino‐β‐Lactams through Palladium(II)‐Catalyzed Sequential Monoarylation/Amidation of C(sp3)H Bonds

“…[5] During the course of our investigations, we found that when KBrO 3 was used as the oxidant, the phenylalanine derivative 2 a was transformed into a-amino-b-lactam 3 a in 16 % yield, presumably through intramolecular C(sp 3 ) À H amidation of the methylene group [Eq. (2) (Phth = phthaloyl)].…”

Ligand‐Promoted Palladium‐Catalyzed C−H Acetoxylation of Simple Arenes

“…The direct oxidation of simple arenes is an attractive process to obtain phenols, which have many applicationsi no rganic synthesis. [6,7] The palladium-catalyzed CÀHa cetoxylation of benzene has been described in the presence of strong oxidants (e.g.,K 2 Cr 2 O 7 ,K 2 S 2 O 8 ), [8] albeit with low catalytic turnover and significant formationo ft he biphenyl byproduct. In 1996, Crabtree reported the use of PhI(OAc) 2 as an oxidant, andi t showedhigher activity and precluded the formation of biphenyl.…”

Sulfonamide‐Promoted Palladium(II)‐Catalyzed Alkylation of Unactivated Methylene C(sp3)H Bonds with Alkyl Iodides

“…[13] Consequently, there is tremendous interest in the synthesis of nonproteinogenic a-amino acids. [14] As part of our efforts to synthesize biologically important organic molecules by direct C(sp 3 )ÀH functionalization, [15] we envisioned that b-alkyl-a-amino acids could be accessed by the alkylation of the b-methylene CÀH bonds of simple a-amino acid derivatives. [16] However, this reaction was rather challenging because of the low reactivity of methylene C(sp 3 ) À H bonds and the tendency of metal alkyl intermediates to undergo side reactions.…”