The first intramolecular aminobromination and aminochlorination of olefins catalyzed by palladium(II) is reported. These reactions use a stoichiometric amount of copper(II) halide salt to aid in halogen transfer and catalyst oxidation. The yields are generally high and the degree of regioselectivity (endo vs exo cyclization) varies with substrate structure. Control experiments were performed to determine the requirements for a catalytic reaction. Solvent, temperature, and the nature of the copper halide salt all effect the course of the reaction.

A new method for the enantioselective synthesis of hexahydro-1H-benz[f]indoles is described. This copper-catalyzed enantioselective intramolecular alkene carboamination process can install vicinal tertiary and quaternary carbon stereocenters with high levels of diastereo-and enantioselectivity. The C-C bond-forming component of the reaction constitutes a C-H functionalization and no electronic activation of the aryl ring that undergoes addition is required. A known 5-HT 1A receptor antagonist was synthesized efficiently using this method.The intramolecular carboamination of alkenes is an attractive method for the synthesis of nitrogen heterocycles.1 This reaction has benefited particularly from methods involving palladium, copper and gold catalysis.2 , 3 In recent years, the catalytic asymmetric carboamination has been actively pursued. One approach involves the doubly intramolecular enantioselective carboamination wherein intramolecular alkene amination is followed by addition of the resulting reactive carbon intermediate to a π-bond tethered through the Nsubstituent. In this manner, Pd(II)2c and Cu(II)3a complexes have catalyzed formation of chiral bicyclic lactams and sultams, respectively.We desired to apply the copper-catalyzed carboamination reaction to the synthesis of other nitrogen heterocycles and believed that the proposed carbon radical intermediate,3c e.g., A (Scheme 1) could add to other nearby π-bonds.This reaction could in principle be (1) chemoselective, choosing radical addition either to an N-arylsulfonyl ring (as previously reported)3a or an aromatic ring at the allylic position (as in Scheme 1), (2) diastereoselective, choosing between formation of either a cis or trans ring fusion, and (3) Our initial forays into the copper-promoted carboamination of N-mesyl substrate 1a were promising. Using 300 mol % of Cu(OAc) 2 , the cis-fused hexahydrobenz[f]indole 2a was obtained in 64% yield with >20:1 diastereoselectivity (Scheme 1).6 Encouraged by this result, we submitted 1a to catalytic, enantioselective conditions.3a To our delight, we obtained a 99% yield and 82% ee, with >20:1 diastereoselectivity using 20 mol % Cu(OTf) 2 , 25 mol % (R, R)-Ph-box, 300 mol % MnO 2 at 120 °C in PhCF 3 for 24 h (Figure 1, 2a).The trimethylsilylethylsulfonyl substrate 1b (R = SES) underwent the reaction with equal efficiency (Figure 1, 2b). Various arylsulfonyl substrates 1c-1g (R = Bs, Ts, PMBS, PCBS, Ns) provided hexahydro-1H-benz[f]indole adducts 2c-2g with even higher enantioselectivity (94-97% ee) and no trace of the sultam3a regioisomer. Substrates 1h-j with para aryl ring substitution (X = F, SMe, OMe) provided uniformly high yields and enantioselectivities.The meta-MeO substrate 3a gave the benz[f]indoles 4 as a 1.5:1 mixture of ortho and para regioisomers (with respect to aryl addition).3cInterestingly, substrates with ortho substitution, 5a and 5b, gave regioisomers 6 and 7 where 7 is the result of a rearrangement where an aryl substituent has apparently shifted to the meta-position. This can be...

Addition of LiNH(2,6-Me2C6H3) (LiNHAr‘) to cis-2,5-bis((tosyloxy)methyl)tetrahydrofuran gave cis-2,5-(Ar‘NHCH2)2(C4H6O) (H2[1]). The reaction between Zr(NMe2)4 and H2[1] yielded [1]Zr(NMe2)2, from which [1]ZrCl2 and [1]ZrMe2 were prepared readily. An unsymmetric relative of H2[1], cis-2,5-(Ar‘NHCH2)(ArNHCH2)(C4H6O) (H2[2]; Ar = 2,6-i-Pr2C6H3), was also prepared via the imine of 5-(hydroxymethyl)furaldehyde. Cations of the type {[1]ZrMe(PhNMe2)}[B(C6F5)4] and {[2]ZrMe(PhNMe2)}[B(C6F5)4], prepared in the reaction between the dimethyl species and [PhNHMe2][B(C6F5)4], could be observed and were stable toward exchange of free and coordinated dimethylaniline on the NMR time scale, while cations prepared in the reaction between the dimethyl species and [Ph3C][B(C6F5)4] did not have interpretable NMR spectra and appeared to be relatively unstable. Nevertheless, poly(1-hexene) that had a molecular weight approximately equal to the amount employed (up to 500 equiv) could be prepared by employing the latter at 0 °C in chlorobenzene.

Ring closure reactions O 0130Palladium (II)-Catalyzed Intramolecular Aminobromination and Aminochlorination of Olefins. -Optimal conditions for the title reaction are developed. The use of a stoichiometric amount of Cu(II) halide to aid in halogen transfer and catalyst oxidation leads to high yields of cyclized products. The degree of regioselectivity varies with the substrate structure. It is found that the solvent, reaction temperature, and the nature of the copper halide influence the course of the reaction. -(MANZONI, M. R.; ZABAWA, T. P.; KASI, D.; CHEMLER*, S. R.; Organometallics 23 (2004) 23, 5618-5621; Dep. Chem., State Univ. N. Y., Buffalo, NY 14260, USA; Eng.) -Klein 11-058

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