Allylic alcohols represent an important and highly versatile class of chiral building blocks for organic synthesis. This Review summarizes the plethora of methods developed for the catalytic asymmetric synthesis of enantioenriched allylic alcohols. These include: dynamic kinetic resolution (DKR/DKAT), nucleophilic 1,2-addition to carbonyl groups, allylic substitution, oxidation of C-H bonds, the addition of O nucleophiles to π systems, reduction of unsaturated carbonyl compounds, and an alternative route from enantioenriched propargylic alcohols. Furthermore, these catalytic asymmetric processes are exemplified by their applications in the syntheses of complex molecules such as natural products and potential therapeutic agents.

Substituted arenes dominate the properties of many natural products, medicines, and materials.[1] Therefore, the development of new methods for direct and selective aromatic functionalization is a persistent challenge for synthetic chemists.[2] A particularly important class of substituted aromatic compounds is the a-aryl carbonyl structure. These molecules represent broadly useful starting materials for complex molecule synthesis, and the basic structural framework is present in a wide range of medicinally relevant molecules.[3] Despite the importance of these structures, surprisingly few direct methods are available to selectively functionalize the arene nucleus in the absence of other groups: aromatic substitution reactions require directing functionality to control reactivity and selectivity; cross coupling processes need pre-installed functional groups; and while the acidity of the CÀH bonds between the arene and carbonyl groups facilitates a wealth of enolate chemistry, it precludes the use of directed ortho-lithiation reactions. [4] A potential solution to some of these limitations has recently been presented through the development of orthoselective Pd II -catalyzed C À H bond functionalization reactions. [5,6] The cyclometalation strategy employed in these transformations, however, cannot be used to facilitate metaor para-functionalization of these molecules due to restrictive geometric constraints. [7,8] The synthetic utility of the generic a-aryl acetic acid motif would be significantly expanded by a methodology that provides direct access to isomeric molecules of potentially beneficial therapeutic value (Scheme 1 A). Herein, we report a copper-catalyzed meta-selective arylation of the a-aryl carbonyl scaffold with diaryliodonium salts that is directed by a remote and versatile Weinreb amide group (Scheme 1 B). This method provides a novel synthetic route to arenes displaying diverse substitution, benzylic chirality and quaternary centers. Its potential is further enhanced through its compatibility with iterative C À H bond functionalization methods that will have broad utility in the synthesis of highly functionalized arenes.As part of our studies towards meta-selective functionalization processes, [8d] we postulated that the location of a carbonyl group plays a key role in determining the selectivity of our Cu II -catalyzed meta-arylation of pivanilides. To test this hypothesis, we speculated that the a-aryl carbonyl would also provide a similar reactivity platform because the carbonyl motif is displayed in a similar position relative to the arene nucleus. Notably, the arene nucleophilicity of the electronically neutral a-aryl carbonyl motif is drastically different to the electron-rich pivanilide.To test whether a-aryl carbonyl compounds could be functionalized at the meta-position, we prepared diethylamide 1 a and treated it with diphenyliodonium triflate and 20 mol % Cu(OTf) 2 in dichloroethane at 70 8C, conditions that are identical to those used for the arylation of pivanilides.[8d]After reacti...

Branching out: The rhodium‐catalyzed enantioselective hydroamination of monosubstituted allenes with anilines permits the atom‐economic synthesis of valuable branched allylic amines. In contrast to previous linear selective allene hydroaminations, a RhI/Josiphos catalyst system (see scheme; cod=1,5‐cyclooctadiene, DCE=1,2‐dichloroethane) allows branched allylic amines to be obtained with perfect regioselectivity, high yield, and good enantioselectivity.

Allylalkohole sind eine wichtige und überaus nützliche Klasse chiraler Bausteine für die organische Synthese. Dieser Aufsatz fasst die Vielzahl an Methoden zur katalytischen asymmetrischen Synthese von enantiomerenangereicherten Allylalkoholen zusammen. Diese umfassen die dynamische kinetische Racematspaltung (DKR/DYKAT), 1,2‐Additionen von Nucleophilen an Carbonylgruppen, allylische Substitutionen, Oxidationen von C‐H‐Bindungen, die Addition von O‐Nucleophilen an π‐Systeme, die Reduktion von ungesättigten Carbonylverbindungen und eine alternative Syntheseroute ausgehend von enantiomerenangereicherten Propargylalkoholen. Darüber hinaus wird der präparative Nutzen dieser katalytischen asymmetrischen Transformationen jeweils am Beispiel ihrer Anwendung in der Synthese komplexer Moleküle wie z. B. Naturstoffen oder potenzieller Therapeutika gezeigt.

Substituted arenes dominate the properties of many natural products, medicines, and materials. [1] Therefore, the development of new methods for direct and selective aromatic functionalization is a persistent challenge for synthetic chemists. [2] A particularly important class of substituted aromatic compounds is the a-aryl carbonyl structure. These molecules represent broadly useful starting materials for complex molecule synthesis, and the basic structural framework is present in a wide range of medicinally relevant molecules. [3] Despite the importance of these structures, surprisingly few direct methods are available to selectively functionalize the arene nucleus in the absence of other groups: aromatic substitution reactions require directing functionality to control reactivity and selectivity; cross coupling processes need pre-installed functional groups; and while the acidity of the CÀH bonds between the arene and carbonyl groups facilitates a wealth of enolate chemistry, it precludes the use of directed ortho-lithiation reactions. [4] A potential solution to some of these limitations has recently been presented through the development of orthoselective Pd II -catalyzed C À H bond functionalization reactions. [5,6] The cyclometalation strategy employed in these transformations, however, cannot be used to facilitate metaor para-functionalization of these molecules due to restrictive geometric constraints. [7,8] The synthetic utility of the generic a-aryl acetic acid motif would be significantly expanded by a methodology that provides direct access to isomeric molecules of potentially beneficial therapeutic value (Scheme 1 A). Herein, we report a copper-catalyzed meta-selective arylation of the a-aryl carbonyl scaffold with diaryliodonium salts that is directed by a remote and versatile Weinreb amide group (Scheme 1 B). This method provides a novel synthetic route to arenes displaying diverse substitution, benzylic chirality and quaternary centers. Its potential is further enhanced through its compatibility with iterative C À H bond functionalization methods that will have broad utility in the synthesis of highly functionalized arenes.As part of our studies towards meta-selective functionalization processes, [8d] we postulated that the location of a carbonyl group plays a key role in determining the selectivity of our Cu II -catalyzed meta-arylation of pivanilides. To test this hypothesis, we speculated that the a-aryl carbonyl would also provide a similar reactivity platform because the carbonyl motif is displayed in a similar position relative to the arene nucleus. Notably, the arene nucleophilicity of the electronically neutral a-aryl carbonyl motif is drastically different to the electron-rich pivanilide.To test whether a-aryl carbonyl compounds could be functionalized at the meta-position, we prepared diethylamide 1 a and treated it with diphenyliodonium triflate and 20 mol % Cu(OTf) 2 in dichloroethane at 70 8C, conditions that are identical to those used for the arylation of pivanilides. [8d] After...