ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
CH-Acidity in α-position to the N-Atom of N, N-Dialkylamides with Sterically Protected Carbonyl Groups Contribution to the Nucleophilic Amino AlkylationSterically protected amides 1 such as the 2,4,6-triisopropyl-benzoic acid derivatives 3, 8b and 10 undergo readily H/Li-exchange with s-butyllithium at the CH3N- or CH2N-groups. The resulting organolithium compounds (cf. 9, 11) are alkylated and hydroxyalkylated with primary haloalkanes, aldehydes, and ketones under chain elongation in the amine position of the amides. The (E/Z)-rotamers of the dialkylamides 7 and 8are separated by chromatography; the amides 4-6, 12, and 13 formally derived from β-hydroxyamines are obtained in the (Z)-form only. The configurational (E/Z)-assignments follow from NMR. and IR. data. The erythro and threo configuration of the two diastereomeric amides 12a and 12b are tentatively concluded from Eu(fod)3-1H-NMR.-shift experiments. The results strongly suggest that the H/Li-exchange takes place regioselectively at the CH—N group which is in cis-position to the C=O double bond (→14). The methyl 2,4,6-tri(t-butyl)benzoate (18) can also be deprotonated to the lithium acyloxymethanide 19 which is trapped by alkylation with 1-iodooctane (→20). - The steric protection of the carbonyl groups in the products 4-8, 10, 12, 13, and 20 prevents their ready hydrolysis to amines and alcohols, respectively. Therefore, triphenylacetic acid derivatives 21 rather than 2,4,6-triisopropylbenzoic acid derivatives for use in the electrophilic substitution of equation (1) are recommended. The trityl group in 21 may be considered a C-leaving-group (C—C protective group, cf. 22, 23). The acetamide 25 reacts readily (→26) and then with electrophiles to give products 27a-c. As shown in the Table, the amides 27 are cleaved under a variety of conditions with formation of triphenylmethane. LiAlH4 produces a tertiary amine, CH3Li a secondary amine, and dissolving alkali metals/naphthalene under aprotic conditions mixtures of secondary amine and its formamide (hydrolysed by acid treatment). Thus the overall process (2) is feasible.
Additional Material:
1 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19780610144
Permalink