Bromocyclization

Figure 5. Y1 adrenocortical cells in culture. Y1 mouse adrenocortical tumor cells (a) in the absence and (b) in the presence of 1 mM 8-bromocyclic AMP overnight. (Photos courtesy of Margaret Wong and Dr. Bernard Schimmer.)...

Bromocyclization of y,S-unsaturated oximes (98) and (99) affords the corresponding bromomethylpyrroline-iV-oxides (100) and (101). Depending on the structural characteristics, the yields vary from 23% to 87% (Scheme 2.40). 

Our attempts at using the pyridine and substituted-pyridine based bromonium ions to induce chirality were not encouraging. As exemplified by the process shown in Figure 4, the enantiomeric excesses (e.e.) in the bromocyclized products formed on reaction of the to(2-(-)-menthylpyridine) bromonium ion 6 with both 4-penten-l-ol and 4-pentenoic acid were only 2.4% and 4.8% respectively (27). The exact reasons for the poor e.e. s observed could be... 

Compounds 38 and 40, prepared by the method shown in Scheme 7 (Section 10.09.6), undergo ready bromocycliza-tion to give oxazolo-fused derivatives 39 and 41 (Equations 8 and 9) <2005JHC755>. In this case, bromination of the thiophene 2-position precedes bromocyclization. Further elaborations are then possible by displacement of the alkyl bromide <2005JHC763>. 

The cyclization of carbamate derivatives of unsaturated amines has proven synthetically useful. Cyclizations of carbamates of allylamines containing a terminal vinyl group give oxazolidinone products (equation 60 and Table 17, entries 1 and 2).99,161 Bromocyclizations of systems with a di- or tri-sub-stituted alkene often give mixtures of oxazolidinones and tetrahydrooxazinones,163 while cyclization of an A -cinnamyl carbamate with phenylsulfenyl chloride gave only the oxazolidinone product.163b,163c The stereochemistry of the cyclization of primary carbamates of either allylic or homoallylic amines is low... 

Several examples of intramolecular solvomercuration of arylalkynes have been reported (equations 81 to 83).200 The mercury moiety can be removed by protiodemetallation or converted to a variety of other functional groups. The use of a methyl ether as the nucleophilic functionality is noteworthy, as is the change in the regioselectivity (equation 82 versus equation 83). A bromocyclization related to equation (83) using a phenylethynylbenzoate ester also gives an isocoumarin derivative via 6-endo cyclization.201 Palladium-catalyzed cyclizations of 3,y-alkynic ketones or 2-methyl-3-alkyn-l-ols to form substituted furans are discussed in Chapter 1.4, Section 3.1.3 in this volume. 

Bromocyclization of the thiocarbamidate generated from f-butylisothiocyanate and 3-buten-2-ol gave oxazolidinone products with slight selectivity for the cis isomer (cis.trans 1.9 1),2271 while iodocycliza-tions of /V-sulfonylated carbamates gave somewhat higher stereoselectivity (equation 117).233... 

The bromocyclization of A/,jV-dialkylaminomethyl ethers of allyl and propargyl alcohols to form oxa-zolidinium salts has been reported, but not used in synthesis.255 The heterocyclization of /V-acylamino-methyl ethers with mercury salts has been used for stereoselective synthesis of a variety of 1,2-amino alcohol systems. These cyclizations form rans-4,5-dialkyl oxazolidine products with good to excellent stereoselectivities (equation 120 and Table 33). As shown by entry 5, 6-endo cyclization predominates (6 3) with an internal double bond of ( )-configuration, but this mode of cyclization is reduced with substrates containing a (Z) double bond and/or allylic oxygen substitution (Table 33, entries 6-9). 

An example of bromocyclization is the stereoselective bromoenol lactonization of alkynoic acids that furnishes either the Z or the E isomer according to the reaction conditions (equation 59)467>468. 

Bromocyclization of allylic thiocarbamidates. Allylic thiocarbamidates (1), prepared as shown, on treatment with this reagent cyclize to bromo carbamates (2). This... 

On the basis of these data, different mechanisms have been suggested. In fact, attack of the nucleophile on a bromonium ion is thought to be the rate determining step of bromocyclization, while in iodocyclization the rate determining step is attack of the nucleophile on the iodine-double bond complex. 

Synthesis of 2-(l-Bromoalkyl)tetrahydrofurans by Bromocyclization of 4-Alkenyl Glycosides... 

Diphenyldibromoselenurane (142) and the ionic derivative 143 were found [70] to be efficient sources of positive bromine for bromolactonization of 4-pentanoic acid (144), bromocyclization of unsaturated alcohols and bromi-nation of 1,3,5-trimethoxybenzene (147) (Eqs. 34 and 35). 

BROMOCYCLIZATION N-Bromosuccini-mide. 2,4,4,6-Tetrabromo-2,5-cyclo-hexadienone. 

The use of bromine mediated cyclization reactions is nicely complimented by iodocyclizations. The mechanism of these reactions proceeds through a similar iodonium ion and the products all bear potential iodide leaving groups. However, as illustrated by the products shown in Scheme 7.1.3, the iodides are all primary and aliphatic suggesting a preference for approach of the hydroxy group from the opposite side as that observed in the case of bromocyclizations. The examples presented in Scheme 7.1.3 were reported by Nicotra, et ai.,3 and demonstrate the utility of these reactions as emphasized by yields as high as 78%. Furthermore, where choices were available, the reactions proceeded with a preference for the formation of five membered rings. 

---