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Abstract Allylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp 3 )–C(sp 3 ) bond-forming reactions.
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Reaction of Carboxylic Acids and Dehydroalanine Allyl Esters via One‐Pot Sequential Decarboxylative Couplings
Abstract A protocol for the iterative decarboxylative cross‐coupling of carboxylic acids with dehydroalanine (Dha) allyl esters is described. A procedure for decarboxylative Giese addition to dehydroalanine allyl esters that avoids 5‐exo‐trig radical cyclization onto the allyl moiety was developed. This results in complex, substituted alanine allyl esters that are poised for a second decarboxylative coupling. Thus, following the photocatalytic decarboxylative alkylation of Dha, the resulting amino acid allyl esters were subjected to decarboxylative allylation under metallaphotoredox/palladium catalysis. The Giese addition and decarboxylative allylation can be performed in one pot simply by triggering the decarboxylative allylation by addition of a palladium catalyst. These one‐pot decarboxylative couplings leverage temporally controlled carboxylate formation to allow controlled, sequential photoredox activation of the carboxylates. The ability to perform sequential, one‐pot photoredox C─C bond formations obviates the need for isolation of intermediates. The final products of these coupling reactions are densely functionalized homoallylic amines and/or unsymmetric, differentiated 1,3‐diamines, both known for their high synthetic value.
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- Award ID(s):
- 2247708
- PAR ID:
- 10625820
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- ChemCatChem
- ISSN:
- 1867-3880
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/cctc.202500696
