Aldehyde Selective Wacker Oxidations of Phthalimide Protected Allylic Amines: A New Catalytic Route to β³-Amino Acids

Abstract

A new method for the synthesis of beta(3)-amino acids is presented. Phthalimide protected allylic amines are oxidized under Wacker conditions selectively to aldehydes using PdCl(2) and CuCl or Pd(MeCN)(2)Cl(NO(2)) and CuCl(2) as complementary catalyst systems. The aldehydes are produced in excellent yields and exhibit a large substrate scope. Beta-amino acids and alcohols are synthesized by oxidation or reduction and subsequent deprotection.

Practical and General Palladium‐Catalyzed Synthesis of Ketones from Internal Olefins

“…Dodecene, a substrate classically prone to isomerization in Wacker chemistry, [14] afforded the desired product in high yield. Allylic phthalimides were recently shown by Feringa and co-workers to afford regioselective formation of the aldehyde, [15] and this outcome was also obtained using our conditions.…”

Palladium-Catalyzed Anti-Markovnikov Oxidation of Allylic Amides to Protected β-Amino Aldehydes

“…12 N-Bocprotected 1-phenylallylamine (1d) was converted to 2d in high yield and selectivity, which contrasts with the formation of the corresponding ketone product under Wacker−Tsuji conditions as reported earlier. 12 Mono-or bis-N-protected 1-phenylallylamines with a series of protecting groups were also converted to the corresponding aldehydes selectively, including pivalic (2c), benzoyl (2e), 2-furoyl (2g), and trichloroacetyl (2h) monoprotected substrates and benzoyl/phenyl (2k) and trifluoroacetyl/p-methoxyphenyl (2l) bisprotected ones. In addition, 4-methoxyphenyl (2f), methyl (2i), pentyl (2j), and ethyl (2m) substituted allylic amines with various protecting groups were converted selectively in good isolated yields (Scheme 3).…”

“…11c The new opportunities arising from Wacker−Tsuji AM oxidations of allylic amines were demonstrated recently by Feringa and co-workers in the AM-selective oxidation of phthalimide-protected allylic amines to their corresponding β 3 -amino aldehydes (Scheme 1). 12 However, extension of this method to any other protecting group resulted in loss of AM selectivity, severely limiting its utility (Scheme 1). Hence, despite its obvious synthetic importance, a general method for the synthesis of protected β-amino aldehydes through AM oxidation of the corresponding allylic amines has, until the present report, not been achieved.…”

Palladium‐Catalyzed anti‐Markovnikov Oxidation of Terminal Alkenes

“…For example, in the case of AM hydroalkylation of allylic amines [19a] the nature of the protecting group is of less relevance than for the corresponding AM oxidations of the substrates. [15] From a mechanistic perspective, two key aspects are apparent. The first is that the formation of an h 2 -palladium complex followed by nucleophilic attack of either water or alcohol is likely to determine the selectivity observed.…”