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Guided desaturation of unactivated aliphatics.

Voica AF, Mendoza A, Gutekunst WR, Fraga JO, Baran PS - Nat Chem (2012)

Bottom Line: The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space.Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis.This 'portable desaturase' (Tz(o)Cl) is a bench-stable, commercial entity (Aldrich, catalogue number L510092) that is facile to install on alcohol and amine functionalities to ultimately effect remote desaturation, while leaving behind a synthetically useful tosyl group.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

ABSTRACT
The excision of hydrogen from an aliphatic carbon chain to produce an isolated olefin (desaturation) without overoxidation is one of the most impressive and powerful biosynthetic transformations for which there are no simple and mild laboratory substitutes. The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space. Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis. In this article, the invention of a directing group to achieve such a transformation under mild, operationally simple, metal-free conditions is outlined. This 'portable desaturase' (Tz(o)Cl) is a bench-stable, commercial entity (Aldrich, catalogue number L510092) that is facile to install on alcohol and amine functionalities to ultimately effect remote desaturation, while leaving behind a synthetically useful tosyl group.

No MeSH data available.


Related in: MedlinePlus

Pioneering studies for alkane desaturationA. Protocol for dehydrogenation employing peroxide-derived O-radicals. B. Breslow’s pioneering study of a remote dehydrogenation. C. Application of Ir-based catalysts toward the desaturation of cyclic alkanes. D. Example of a Pd-catalyzed guided desaturation reaction.
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Figure 1: Pioneering studies for alkane desaturationA. Protocol for dehydrogenation employing peroxide-derived O-radicals. B. Breslow’s pioneering study of a remote dehydrogenation. C. Application of Ir-based catalysts toward the desaturation of cyclic alkanes. D. Example of a Pd-catalyzed guided desaturation reaction.

Mentions: Of all the functional groups in organic chemical space, the olefin must be regarded as one of the most privileged from the vantage point of utility in synthesis. As a result, methods for olefin synthesis and functionalization have been extensively developed and applied in both academic and industrial sectors. Most olefin-forming reactions rely on preoxidized starting materials and fall into four main categories: functionalization of ketones or aldehydes (aldol condensation, Wittig olefination, etc.); modification of other alkenes (olefin metathesis, metal-catalyzed coupling reactions, etc.); reductive transformations of alkynes (stereoselective reduction, reductive coupling, etc.); or synthesis by elimination reactions (from alcohols, halides, etc.).1 A less explored strategy for olefin synthesis is the direct desaturation of the parent alkane. Within this category, the dehydrogenation of activated aliphatics (leading to enones, dienes, styrenes, etc.), generally a more facile process, has been broadly utilized and continues to be investigated.2 In contrast, the efficient oxidation of unactivated alkanes directly to alkenes remains an unmet challenge and approaches to this problem have only rarely surfaced in methodological studies.3 Select examples of reported strategies for alkane dehydrogenation are shown in Figure 1. Among these, Breslow’s groundbreaking work awakened the community to the strategic value of a remote desaturation reaction and provided extensive studies on steroid frameworks.4–6 In general, these approaches employ high-energy radicals (Figure 1A, B)4,7 or transition metals (Figure 1C, D)8–13 to overcome the high kinetic stability of the C–H bond. While these pioneering studies have clarified the difficulties in achieving such a transformation (regiocontrol, product isolation, functional group tolerance), most of these methods lack the generality and practicality required for wide use in complex systems. Important limitations include the use of inconvenient starting materials (e.g., peroxides), poor substrate scope, overoxidation of the resulting olefin, large substrate excesses or harsh reaction conditions. Therefore, the invention of a broadly applicable, mild protocol to achieve regio- and chemoselective desaturation of unactivated aliphatics remains highly desirable.


Guided desaturation of unactivated aliphatics.

Voica AF, Mendoza A, Gutekunst WR, Fraga JO, Baran PS - Nat Chem (2012)

Pioneering studies for alkane desaturationA. Protocol for dehydrogenation employing peroxide-derived O-radicals. B. Breslow’s pioneering study of a remote dehydrogenation. C. Application of Ir-based catalysts toward the desaturation of cyclic alkanes. D. Example of a Pd-catalyzed guided desaturation reaction.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3405363&req=5

Figure 1: Pioneering studies for alkane desaturationA. Protocol for dehydrogenation employing peroxide-derived O-radicals. B. Breslow’s pioneering study of a remote dehydrogenation. C. Application of Ir-based catalysts toward the desaturation of cyclic alkanes. D. Example of a Pd-catalyzed guided desaturation reaction.
Mentions: Of all the functional groups in organic chemical space, the olefin must be regarded as one of the most privileged from the vantage point of utility in synthesis. As a result, methods for olefin synthesis and functionalization have been extensively developed and applied in both academic and industrial sectors. Most olefin-forming reactions rely on preoxidized starting materials and fall into four main categories: functionalization of ketones or aldehydes (aldol condensation, Wittig olefination, etc.); modification of other alkenes (olefin metathesis, metal-catalyzed coupling reactions, etc.); reductive transformations of alkynes (stereoselective reduction, reductive coupling, etc.); or synthesis by elimination reactions (from alcohols, halides, etc.).1 A less explored strategy for olefin synthesis is the direct desaturation of the parent alkane. Within this category, the dehydrogenation of activated aliphatics (leading to enones, dienes, styrenes, etc.), generally a more facile process, has been broadly utilized and continues to be investigated.2 In contrast, the efficient oxidation of unactivated alkanes directly to alkenes remains an unmet challenge and approaches to this problem have only rarely surfaced in methodological studies.3 Select examples of reported strategies for alkane dehydrogenation are shown in Figure 1. Among these, Breslow’s groundbreaking work awakened the community to the strategic value of a remote desaturation reaction and provided extensive studies on steroid frameworks.4–6 In general, these approaches employ high-energy radicals (Figure 1A, B)4,7 or transition metals (Figure 1C, D)8–13 to overcome the high kinetic stability of the C–H bond. While these pioneering studies have clarified the difficulties in achieving such a transformation (regiocontrol, product isolation, functional group tolerance), most of these methods lack the generality and practicality required for wide use in complex systems. Important limitations include the use of inconvenient starting materials (e.g., peroxides), poor substrate scope, overoxidation of the resulting olefin, large substrate excesses or harsh reaction conditions. Therefore, the invention of a broadly applicable, mild protocol to achieve regio- and chemoselective desaturation of unactivated aliphatics remains highly desirable.

Bottom Line: The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space.Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis.This 'portable desaturase' (Tz(o)Cl) is a bench-stable, commercial entity (Aldrich, catalogue number L510092) that is facile to install on alcohol and amine functionalities to ultimately effect remote desaturation, while leaving behind a synthetically useful tosyl group.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

ABSTRACT
The excision of hydrogen from an aliphatic carbon chain to produce an isolated olefin (desaturation) without overoxidation is one of the most impressive and powerful biosynthetic transformations for which there are no simple and mild laboratory substitutes. The versatility of olefins and the range of reactions they undergo are unsurpassed in functional group space. Thus, the conversion of a relatively inert aliphatic system into its unsaturated counterpart could open new possibilities in retrosynthesis. In this article, the invention of a directing group to achieve such a transformation under mild, operationally simple, metal-free conditions is outlined. This 'portable desaturase' (Tz(o)Cl) is a bench-stable, commercial entity (Aldrich, catalogue number L510092) that is facile to install on alcohol and amine functionalities to ultimately effect remote desaturation, while leaving behind a synthetically useful tosyl group.

No MeSH data available.


Related in: MedlinePlus