Abstract:Unprotected -(het)aryl--fluoroalkyl -amino acids and their -hydroxy derivatives can be readily obtained using a decarboxylative Mannich-type reaction without protection/deprotection steps. This protocol utilizes lithium hexamethyldisilazide and (het)arylfluoroalkyl ketones to generate NH-ketimine intermediates. The mild reaction conditions allow the preparation of original fluorinated -amino acids as useful building blocks in a practical and scalable manner.
“…Shortly after, the emergence of organocatalysis as a powerful tool for the formation of C−C bonds has extended their use in aldol, [87] or Mannich‐type reactions with preformed imines, [88–91] in elegant and selective transformations. Other analogues such as β‐ketoacids, [92] or malonic acids, [93] have been described in similar transformations.…”
Section: Aldol‐ and Mannich‐type Reactionsmentioning
Substituted malonic acid half‐oxyesters (SMAHOs) constitute an original family of malonic acid derivatives. They could be mostly used as pro‐nucleophiles through decarboxylative processes, making them enolate equivalents for the elaboration of greener methodologies. In addition to the native ester function, the presence of a substituent on the malonic position affords additional opportunities for structural diversification. These reagents are particularly well‐suited for the development of organocatalyzed processes, which has recently led to olefination and addition reactions as relevant synthetic routes to elaborated structures under mild conditions.
“…Shortly after, the emergence of organocatalysis as a powerful tool for the formation of C−C bonds has extended their use in aldol, [87] or Mannich‐type reactions with preformed imines, [88–91] in elegant and selective transformations. Other analogues such as β‐ketoacids, [92] or malonic acids, [93] have been described in similar transformations.…”
Section: Aldol‐ and Mannich‐type Reactionsmentioning
Substituted malonic acid half‐oxyesters (SMAHOs) constitute an original family of malonic acid derivatives. They could be mostly used as pro‐nucleophiles through decarboxylative processes, making them enolate equivalents for the elaboration of greener methodologies. In addition to the native ester function, the presence of a substituent on the malonic position affords additional opportunities for structural diversification. These reagents are particularly well‐suited for the development of organocatalyzed processes, which has recently led to olefination and addition reactions as relevant synthetic routes to elaborated structures under mild conditions.
“…The synthesis of β-fluoroalkyl β-amino acids was reported by Gillaizeau and co-workers in 2019 ( Scheme 16 ) [ 75 ]. They employed lithium hexamethyldisilazide and a selection of arylfluoroalkyl ketones ( 65 ) to generate NH-ketimine intermediates ( 66 ) that could then undergo decarboxylative Mannich-type reactions.…”
“…These amino acids were further demonstrated to be applicable in the synthesis of novel heteroaromatic systems [ 72 ]. Scheme 16 Synthesis of β-fluoroalkyl β-amino acids, Gillaizeau and co-workers [ 75 ]. …”
“…Catalytic amination of alcohols with ammonia through a borrowing hydrogen process, which involves N -unsubstituted imines as intermediates, is also not entirely covered in this review because excellent reviews in this field are available . In addition, although N -trialkylsilyl imines can be used for obtaining N -unprotected amines through addition reactions followed by hydrolysis of weak Si–N bonds during the workup process, these examples are not discussed in detail, as they require prerequisite installation of a trialkylsilyl group as the protective group.…”
Catalytic addition reactions to N-unsubstituted (N-unprotected) imines can provide a more straightforward synthesis of amines. This direct process eliminates the unnecessary protecting-group manipulations that are required with N-substituted (N-protected) imines and can contribute to the development of green chemistry. Although their use has been limited due to difficulties associated with the nature of N-unsubstituted imines, recently developed catalytic methods enable the use of N-unsubstituted imines as electrophiles in various catalytic addition reactions. To facilitate an understanding of the state of the art development of synthetic methodologies, herein we review recent progress on catalytic addition reactions to N-unsubstituted imines. We begin with an overview of the chemistry of N-unsubstituted imines, followed by a summary of recent progress categorized according to the reaction type. We hope this review will help to stimulate further development of greener syntheses of nitrogen-containing compounds.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
