- N-Methyl Allylic Amines from Allylic Alcohols by Mitsunobu Substitution Using N-Boc Ethyl Oxamate
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We report the practical, scalable synthesis of a range of N-methyl allylic amines. Primary and secondary allylic alcohols underwent a regioselective Mitsunobu reaction with readily accessible N-Boc ethyl oxamate to deliver the corresponding N-Boc allylic amines, including in enantiopure form via stereospecific substitution. Subsequent N-methylation and Boc deprotection without chromatography yielded the amine products as hydrochloride salts. This method solves the problem of converting commercially available alcohols into often volatile N-methyl allylic amines, many of which have limited commercial availability.
- Van Veen, Branca C.,Wales, Steven M.,Clayden, Jonathan
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p. 8538 - 8543
(2021/06/30)
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- Direct Synthesis of Highly Substituted Pyrroles and Dihydropyrroles Using Linear Selective Hydroacylation Reactions
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Rhodium(I) catalysts incorporating small bite-angle diphosphine ligands, such as (Cy2P)2NMe or bis(diphenylphosphino)methane (dppm), are effective at catalysing the union of aldehydes and propargylic amines to deliver the linear hydroacylation adducts in good yields and with high selectivities. In situ treatment of the hydroacylation adducts with p-TSA triggers a dehydrative cyclisation to provide the corresponding pyrroles. The use of allylic amines, in place of the propargylic substrates, delivers functionalised dihydropyrroles. The hydroacylation reactions can also be combined in a cascade process with a RhI-catalysed Suzuki-type coupling employing aryl boronic acids, providing a three-component assembly of highly substituted pyrroles. Down the line: Rhodium catalysts featuring small-bite-angle bisphosphine ligands allow the linear-selective combination of aldehydes and propargylic amines (see scheme). The resultant γ-amino-enone products are converted in situ to a diverse range of substituted pyrroles. Allylic amine substrates can also be employed, leading in these cases to dihydropyrrole products.
- Majhail, Manjeet K.,Ylioja, Paul M.,Willis, Michael C.
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supporting information
p. 7879 - 7884
(2016/06/09)
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- NOVEL BICYCLIC SULFONAMIDES FOR USE AS GLUCOCORTICOID RECEPTOR MODULATORS IN THE TREATMENT OF INFLAMMATORY DISEASES
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Compounds of formula (I): or a pharmaceutically acceptable salt thereof; compositions comprising them, processes for preparing them and their use in medical therapy (for example modulating the glucocorticoid receptor in a warm blooded animal).
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Page/Page column 52
(2008/06/13)
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- Fe(II)-catalyzed imidation of allyl sulfides and subsequent [2,3]- sigmatropic rearrangement. Preparation of α-branched N-tert-butyloxycarbonyl (Boc)-protected N-allylamines
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Allyl aryl sulfides 1 and 5 were shown to undergo an imidation/[2,3]- sigmatropic rearrangement reaction upon treatment with N-tert- butyloxycarbonyl azide (BocN3) and catalytic amounts of FeCl2 in CH2Cl2. The N-Boc-protected N-allyl sulfenamides 3 and 21 were obtained in yields between 48 and 75% (12 examples). Whereas the reaction is well suited for the transformation of α-unbranched sulfides to α-branched sulfenamides, the enantiomerically pure α-branched sulfides 10 and 13 reacted sluggishly. The corresponding sulfenamides 22 and 23 were obtained in only moderate enantiomeric excess (36-39% ee). A reaction mechanism is proposed that postulates the intermediacy of an N-Boc-substituted Fe(IV)-nitrene complex 14 acting as the imidation reagent in the catalytic cycle. Possible side reactions are discussed. The benzenesulfenamides 3 were further converted into N-Boc-N-allylamines 4 by removal of the phenylsulfanyl group. Bu3SnH in benzene was found to be the reagent of choice for the deprotection of α- branched amines that bear a secondary allyl substituent (five examples, 71- 93% yield). This method failed for the α-branched amines 3i-k with a tertiary allyl substituent. The phenylsulfanyl group was finally removed with P(OEt)3/NEt3 in CH2Cl2 (three examples, 43-62% yield).
- Bach, Thorsten,Koerber, Christina
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p. 2358 - 2367
(2007/10/03)
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