Diels−Alder Approach for the Construction of Halogenated, o-Nitro Biaryl Templates and Application to the Total Synthesis of the Anti-HIV Agent Siamenol

Abstract

A rapid Diels-Alder approach to halogenated biaryl templates is described. These biaryl templates are available in two steps from the corresponding aromatic aldehydes. The scope of subsequent Suzuki couplings on the biaryl chlorides is explored. Good tolerance for both electron-donating and electron-withdrawing groups in the coupling process can be achieved. Further functionalization of the biaryl templates is described. Hydrogenation of the nitro moiety with concomitant removal of the benzyl ether yields the o-anilino, o-phenolic polyaryls. Selective reduction of the nitro group can be accomplished. Alternatively, the benzyl ether can be selectively removed under Lewis acidic conditions. The utilization of the Diels-Alder adducts for the synthesis of a series of chlorinated carbazoles via the Cadogan cyclization is also demonstrated. Finally, application of this technology to the total synthesis of siamenol, an anti-HIV agent, is reported.

Unusual Reactivity of Aryl Aldehydes with Triethyl Phosphite and Zinc Bromide: A Facile Preparation of Epoxides, Benzisoxazoles, and α‐Hydroxy Phosphonate Esters

“…The reaction of 2,3-dichloro-6nitrobenzaldehyde (3d, [31] 0.5 g, 2.20 mmol) with triethyl phosphite (1.13 g, 6.82 mmol) in the presence of ZnBr 2 (0.05 g, 0.22 mmol) at room temperature for 10 min followed by workup using general procedure B gave 4,5-dichlorobenzo Bromoaldehyde 3e and Dibromoaldehyde 3f: To a solution of 6-nitrobenzo[d][1,3]dioxole-5-carbaldehyde (1 g, 5.12 mmol) in concentrated H 2 SO 4 (8 mL) was added NBS (1.82 g, 10.25 mmol) at 0°C for 10 min, and the reaction mixture was warmed to room temperature and stirred for 3 h. Upon consumption of the starting material (monitored by TLC), the reaction mass was poured over crushed ice (100 g), and the resulting mixture was extracted with ethyl acetate (2 ϫ 15 mL). The combined organic extracts were washed with brine solution (2 ϫ 30 mL) and dried with Na 2 SO 4 .…”

Synthetic approaches to regiospecifically mono‐ and dilabelled arenes

“…Propiolic acid is commercially available in both 13 C and 14 C labelled forms, providing a comparatively simple access into specifically substituted point‐labelled arenes. The process tolerates a variety of substituents on the acetylene including aryl,129 boronate,130 hydroxyalkyl,131 phosphonium,132 silyloxy133 and trihalomethyl groups 134. Dienes used include Danishefsky's diene,126 pyranones including those bearing acylamino135 and arylthio substituents,136 diene‐substituted α‐amino acids137 and carbohydrate‐derived homochiral dienes 138.…”

Arrangement of Proteinogenic α‐Amino Acids on a Cyclic Peptide Comprising Alternate Biphenyl‐Cored ζ‐Amino Acids

“…Pd(PPh 3 ) 4 was prepared as decribed . The analytical data of compounds 3 and 5 were referred to the literature . Compounds 9 and 10 were intermediates for the synthesis of compound 11 , and thus their full analytical data were not collected.…”