A mild and practical method for the regioselective synthesis of N-acylated 3,4-dihydropyrimidin-2-ones. New acyl transfer reagents Kamaljit Singh * and Sukhdeep Singh Organic Synthesis Laboratory, Department of Applied Chemical Sciences and Technology, Guru Nanak Dev University, Amritsar 143 005, India Received 21 July 2006; revised 29 August 2006; accepted 7 September 2006 Available online 2 October 2006 Abstract—The treatment of 3,4-dihydropyrimidin-2-ones with n-BuLi at À78 °C, followed by quenching with various electrophiles furnished N3-substituted derivatives, regioselectively. Further, N1,N3-diacyl derivatives were found to transfer N1-acyl groups to nucleophilic sites. Ó 2006 Elsevier Ltd. All rights reserved. 4-Aryl-3,4-dihydropyrimidin-2-ones (Biginelli com- pounds, DHPMs) represent an azaheterocyclic system of remarkable pharmacological profile. 1 DHPMs are found in natural products and find applications as calcium channel modulators, a 1a -adrenergic receptor antagonists, mitotic kinesin inhibitors, and hepatitis B virus replication suppressors. Several marine derived natural products which are inhibitors of HIV gp- 120CD4, also contain the DHPM core. Although a large number of DHPM derivatives have been prepared in single-pot Biginelli multi-component reaction (MCR), and its variants, a greater number of very interesting heterocycles have been obtained by the chemical func- tionalization of the six (N1, C2, N3, C4, C5 and C6) positions around the DHPM core. 2 Recently, we revealed that Biginelli DHPMs can be lithiated at the C6 methyl and thus elaborated regioselectively, with a wide variety of electrophiles. 3 Regioselective N3-functionalization (acylation, alkoxy- carbonylation, and alkylation) of DHPMs is of considerable importance for the preparation of N3-substituted DHPMs, related to the biologically important compounds SQ 32,926 1, SQ 32,547 2, and L-771,668 3. 1a N H N Me O NO 2 O NH 2 O i-PrO 1 N H N O F O NH(CH 2 ) 2 CH 2 O MeO 3 F OMe N N N H N Me S O O O i-PrO 2 CF 3 N F A survey of the literature revealed a single example of the direct N3-acylation (DMF/POCl 3 ) of a C-4 aryl- substituted DHPM, where the N3-formylated product (12% yield) was attended by a 6H-1,3-thiazine derivative (47% yield). 4 A rather high temperature (100–180 °C) microwave-aided acylation technique, employing poly- mer-supported reagents and scavengers provided an attractive method, 5 but lacked the economy and simplic- ity of a one-pot reaction. In contrast to the acylation, the alkoxycarbonylation of Biginelli DHPMs with, for example, ethyl chloroformate and base has proved prob- lematic leading to mixtures of N1 and N3 substituted products depending on the substitution pattern around the DHPM ring. 6 Also, N3-monoalkylated DHPMs 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.09.039 Keywords: Biginelli compounds; Calcium channel modulators; Acyl transfer reagent. * Corresponding author. Tel.: +91 0183 2258853/2258802–09x3508; fax: +91 0183 2258819–20; e-mail: kamaljit19in@yahoo.co.in Tetrahedron Letters 47 (2006) 8143–8146