Endo bromine atom

The hitherto unknown tropylium ion isomer (317) has been generated from both (315) and (316). ° In carbon tetrachloride at 80°C, (315) affords (31 probably by disrotatory ring cleavage and loss of the endo-bromine atom. Although (317) is stable, silver-ion-assisted solvolysis of (316) causes partial rearrangement of (317) into the norbornene manifold (Scheme 40). 

This is again the result of steric shielding by the trichloromethyl group, which causes the bromine atom to be abstracted from the endo face of the intermediate radical. 

The formation of alkyl shifted products H and 14 can be explained in terms of the formation of endo-intermediate 21 formed by endo attack of bromine to 2 (Scheme 4). The determined endo-configuration of the bromine atom at the bridge carbon is also in agreement with endo-attack. Endo-Intermediate 21 is probably also responsible for the formation of cyclopropane products 12 and 15. The existence of cyclopropane ring in 12 and 15 has been determined by and 13c NMR chemical shifts and especially by analysis of cyclopropane J cH coupling constants (168 and 181 Hz). On the basis of the symmetry in the molecule 12 we have distinguished easily between isomers 12 and 15. Aryl and alkyl shift products IQ, H, and 14 contain benzylic and allylic bromine atoms which can be hydrolized easily on column material. 

Yaodong Huang, while pursuing the synthesis of ( + )-berkelic acid (69), reported a diastereoselective cycloaddition using method H that leads to another type of 5,6-aryloxy spiroketals (Fig. 4.36).32 For example, addition of three equivalents of t-butyl magnesium bromide to alcohol 70 in the presence of the exocyclic enol ether 71 proceeds in a 72% yield to the spiroketal 72 with a 4.5 1 selectivity favoring the endo approach (Fig. 4.36). Additional experiments suggest the bromine atom decreases the HOMO-LUMO band gap and improves diastereoselectivity. 

Changing the bromine atom in 3-bromo-norbornanones from endo to exo position causes the signal of C-3 to shift upheld about 6 ppm. 

The situation is more complicated in the case of 5-bromohexopyranose derivatives, because products of both endo- and exo-elimination may be formed, and available evidence indicates that, with 5-bromo-/ -D-glucopyr-anose esters, base-catalyzed elimination favors the production of endo-alkenes following loss of axial hydrogen and bromine atoms. Alternatively, treatment with zinc-acetic acid gives, mainly, the products of exo-elimination.90 From the acetate 164 (R = Ac) and the benzoate 164 (R = Bz), the 4-enes (165, R = Ac, Bz) were both obtained in 65% yield following treatment with 1,5-diazabicyclo[5.4.0]undec-5-ene, whereas zinc - acetic acid afforded the 5-enes (166, R = Ac, Bz) in 59 and 67% yield. The isomeric endo products 167 (R = Ac, Bz) were isolated in 15 and 11% yield, and, from the... 

The dominant supramolecular synthon present in these compounds is the pi-halogen dimer (PHD) interaction [22], This efficient packing motif results from two inversion-related host molecules packing such that one bromine atom from each is situated in the cleft of its V-shaped partner (Figure 3), in addition to aromatic endo, endo-facial interaction. 

Satisfactorily, the 1-endo closure became the predominat route when a temporary substituent was introduced at the 6-exo position of the alkene acceptor, a tactic previously used in similar 1-endo cyclizations involving aryl <4TL2335>, vinyl <05JOC519> or alkyl <06OL831> radicals. Hence, cyclization of selenoester 30b, which incorporates a 2-bromo-2-propenyl instead of an allyl moiety, led to the tricyclic substructure of mersicarpine 32 in a synthetically acceptable 62% yield, pyridoindole 31 being now the minor product (19%). The excess hydride ensured the final reductive removal of the bromine atom after the cyclization step <07JOC4562>. 

As the azocinoindole 40 constitutes the tricyclic substructure of the indole alkaloid apparicine , we attempted to improve the cyclization yield. Satisfactorily, the regioselectivity was completely switched to the 8-endo mode when the alkene acceptor was substituted at the internal position by a bromine atom. Thus, cyclization of selenoester 43 led to the desired target 40 as the only reaction product in 75% yield. Clearly, the bromine atom not only sterically prevented the competitive 1-exo attack, but also benefited the cyclization by activation of the double bond. It should be noted that similar halogen-controlled 8-endo cyclizations are known in the literature, but involving amidyl-type radicals <06OL2647>. 

The 2-pyrones 4 and 5 with a bromine atom substituted at the C3 or C5 position, respectively, are particularly versatile 1,3-diene synthons, which can readily undergo [4-1-2] cycloadditions to give the cycloadducts 6 and 7 with high regio- and endo/exo selectivity under milder conditions than the parent 2-pyrone (Scheme 4) <91TL5295 92TL7839>. They are viable synthetic equivalents of the parent 2-pyrone as the bromine atom can be reductively removed after cycloaddition. Additionally, they exhibit ambident enophilic character and are capable of undergoing both normal and inverse electron demand cycloadditions. 

The fran -fused decalin system is conformationally rigid and the stereochemistry of the product indicates that the initial addition of the trichloromethyl radical is from an axial direction. This is expected on stereoelecfronic grounds because the radical should initially interact with the ir orbital. The axial trichloromethyl group then shields the adjacent radical position and directs the bromine abstraction in the trans sense. Addition of bromotrichloromethane to norbornene is also anti. This is again the result of steric shielding by the trichloromethyl group, which causes the bromine atom to be abstracted from the endo face of the intermediate radical. 

Studies on intramolecular cyclizations using pathway 0 were mainly carried out with the bicyclic endo-2-amine 231 having an exo-bromine atom at C(6) as leaving group. 

The latter process is well modelled by the halogenation of the tetrafluoroben-zonorbomadiene 293. The stereospeciHc endo-side attack of Br and the absence of Wagner-Meerwein rearrangement in reactions with 7-isopropylidentetrafluoro-benzonorbornadiene are well accoimted for by the structure of the homoallylic ion A which is not converted into the homobenzylic ion. The fact that the bromine atoms go in to the most sterically unfavourable cis-vincinal position is difficult to explain if the intermediate cation has the classical structure B. 

Bennasar also recently extended their interest in the cyclization of A -alkenyl substituted 2-indolylacyl radicals towards the annulation of larger rings [126]. A 7-endo-mg closure was observed when brotnovinyl substituted seleno ester 237 was treated with excess tin hydride in EtaB. In addition to the desired azepino[3,2-I>] indole 238, the 6-exo cyclization product 239 was observed as the minor product, with both products showing no evidence of the bromine atom in their strucmres. Previous attempts at this cyclization using a tethered allyl moiety, rather than the 2-bromo-2-propenyl tether, also gave the azepinoindole but only as the minor product. 

Azocino[3,2-6]indoles were obtained when seleno ester precursors bearing 3-butenylamino and allylaminomethyl chains on the C-3 position of the indole were subjected to the same reductive radical conditions used previously with indole 237. Inclusion of a bromine atom on the alkene acceptor gave the most rewarding result (shown below) at a hydride concentration of 0.02 M yielding 75% of the %-endo product 241, without the detection of any products, formed as a result of reductirm or the alternative 1-exo cyclization. This method proved to be a nice complement to the ring-closing metathesis protocol used in this laboratory to effect similar cyclizations and recently resulted in the total synthesis of apparicine [126, 127]. 

Interestingly, another example of a [1,5]-radical translocation coupled with an unusual 5-endo-trig radical cyclization was reported in a structurally different system (Scheme 10). In this case, the a-bromovinyl radical abstracted a hydrogen either from (TMSjsSiH to give vinyl bromide in 25% yield or from the anomeric position to generate the C-1 radical which underwent an unusual 5-endo-trig cyclization onto the proximal double bond to generate an anomeric mixture of spironucleosides after bromine atom ejection. 

Another Lewis acid-catalyzed atom-transfer domino radical cyclization, to produce various bicyclic and tricyclic ring skeletons, has been developed by Yang and coworkers [54]. Reactions of the a-bromo-(3-keto ester 3-125 with Yb(OTf)3 and Et3B/02 led to the bicycle 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a (>-endo-Irig and 5-exo-trig cyclization after initial abstraction of the bromine... 

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