Bromide intermediate

In 2003, Williams and Mander reported a method designed to access the hetisine alkaloids (Scheme 1.3) [27]. This approach, based upon a previously disclosed strategy by Shimizu et al. [28], relied on arylation of a bridgehead carbon via a carbocation intermediate in the key step. Beginning with (1-keto ester 46, double Mannich reaction provided piperidine 47. Following a straightforward sequence, piperidine 47 was transformed to the pivotal bromide intermediate 48. In the key step, bromide 48 was treated with silver (I) 2,4,6-trinitrobenzenesulfonate in nitro-methane (optimized conditions) to provide 49 as the most advanced intermediate of the study, in 54 % yield. 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

HEXYL BROMIDE. Intermediate, for introduction of hexyl group. 

For the synthesis of CIO carba derivatives, a better leaving gronp than hydroxyl is nsnally preferred. The anomeric finoride , bromide, acetate, benzoate and phenyl-snlphonyl gronps have all been nsed and some of the chemistry that has been achieved is shown in Scheme 25. AllylsUanes tend to provide /S-confignred prodncts by axial attack on the oxoninm ion species (Scheme 25C) whereas larger nncleophiles snch as electron-rich aromatics add by attack on the a face (Scheme 25D). For nitrogen nncleophiles, Haynes and CO workers have employed the CIO anomeric bromide intermediate that gives the ClO-a hemi-aminal prodncts (Scheme 25E), some of which exhibit remarkable stability (Chart 1) . ... 

An inter-intra-intramolecular carbopalladation cascade, initiated by the alkenylpalladium bromide intermediate from /3-bromostyrene 74 inserting into one of the triple bonds of the diyne 73, yields the ring-annelated fulvene derivative 75 (Scheme 22). ... 

Similar reactions involving intermolecular quaternization and quaternization/elimination of methyl bromide, using an appropriate alkyl bromide intermediate, led to the formation of the piroarsinolinium bromides (88) and (89) respectively, which were characterized as the iodides. In the case of (88), resolution into optical isomers was also achieved via the (-)-methoxyacetates to give the enantiomorphic iodides ([A/] 132° CHC13) <60JCS9>. 

Secondary and tertiary alkyl bromides react with active zinc at ambient temperature. However, the reaction time for the oxidative addition can be shortened by heating the reaction mixture at reflux in THF. Methyl 3-bromo-butyrate gives the organozinc bromide intermediate upon reaction with active zinc and reacts with 2-cyclohexen-l-one to afford the 1,4-addition product (Protocol 6, Scheme 2.3).14... 

Warmus et al. (121) recently reported the multivariate optimization of reaction conditions for the synthesis of a known class of ICE (interleukin-ip converting enzyme) inhibitors, represented by compound 9.70. The structure of the compound and the synthetic route, starting from the key bromide intermediate 9.71, are reported in Fig. 9.29 (the acetylvaline moiety of 9.70 was replaced during the optimization with an Fmoc carbamate). 

The value of the silicon substituent in promoting the carbolithiation is illustrated by comparing the reactions of hex-l-en-3-yne 42 and l-(trimethylsilyl)but-3-en-l-yne 43 with u-BuLi in ether, as shown in Scheme 7-33. However, to be synthetically useful, the metallotropic equilibrium between the lithioallene and the lithioalkyne should be displaced by reaction with an electrophile in favor of only one derivative. Thus, the addition of zinc salts to a mixture of propargyl-allenyllithium derivatives quantitatively leads to the allenylzinc bromide intermediate (Scheme 7-34) and reaction of the latter with electrophiles, via an 8 2 process [34], only gives the propargyl derivative (Scheme 7-34). 

The enantioselective total synthesis of the manzamine alkaloid ircinal A was completed in the laboratory of S.F. Martin utilizing a novel strategy. A domino Stille/Diels-Alder reaction was used to assemble the ABC ring core of the natural product. The vinyl bromide intermediate reacted with vinyl tributylstannane in the presence of Pd to afford the 1,3-diene moiety, which cyclized via an intramolecular Diels-Alder reaction to give the ABC core. 

From 94, several compounds were generated such as the 3-thioalkyl compounds 96 (40-67%) by reaction with alkyl bromides. Intermediate 94 was also treated with HCl, iodine, 1,3-dibromopropane or with ethyl chlorocar-bonate affording the mercaptane 97 (68%), the disulfide 98 (45%, n = 0), compound 99 (37%, = 3) and the thiocarbonate 100 (67%), respectively. By a partial hydrolysis of the nitrile group with H2SO4 at reflux, carboxamides lOla-b (92%) were prepared from 96. The same reagents 96 can be transformed into methyl esters 102 (Scheme 26). 

A general method for the cyclization of an unactivated 1,1-disubs-tituted alkene to the corresponding cyclopentene has been described. Bromination followed by the addition of KHMDS in the same pot gave the vinyl bromide intermediate, which reacted further in situ to give the alkylidene carbene. This is then inserted in a 1,5-fashion into a C-H bond to yield the corresponding cyclopentene (eq 44). KHMDS proved to be superior in this process as compared to LiHMDS and NaHMDS. 

The synthesis of imino-penam and -cephem derivatives has also been investigated using the [2 + 2] cycloaddition of ketenimines to Schiff bases as the key-step [24]. N-(aryl) and N-(alkyl)ketenimines are not electrophilic enough to react with Schiff bases. On the other hand, iV-(tosyl)ketenimines 25 were susceptible to nucleophilic attack by imines (Scheme 9). They were readily generated in situ from the corresponding sulphimides 23. The a-bromo-iminium bromide intermediates 24 reacted with Schiff bases and triethylamine to give JV-(tosyl)azetidin-2-imines 26. 

Bromo-2-fluoro biphenyl intermediate, foam builders Alkenyl succinic anhydride intermediate, food additives Soy acid Stearyl alcohol intermediate, food emulsifiers Caprylic/capric acid Tallow acid intermediate, food supplements (tablet form) Cetyl alcohol intermediate, food wrap Vinylidene chloride monomer intermediate, fragrances p-t-Butyl toluene t-Butyl-m-xylene Citral Cyclopentanone Diethyl toluene diamine Dimethyl hexynediol 1,2-Methylenedioxybenzene 2-Methylpentanal Myrcene n-Propyl bromide intermediate, fragrances cosmetics Acetic anhydride n-Butyraldehyde n-Butyric acid Butyric anhydride 2-Ethylhexoic acid Isobutyric anhydride 2-Methylpropanal Propionic anhydride intermediate, fragrances personal care Butyric anhydride Isobutyric anhydride intermediate, free-radical polymerization initiators... 

The mechanism for this variation is believed to go through an acylimidoyl chloride/bromide intermediate 18 the intermediate then attacks the aldehyde to give 4-halo-oxazoles of structure 20. 

Scheme 3.14 Reaction of Zn with optically active bromides intermediate radicals promote racemization.

In the above-mentioned Heck-type cascade tetracyclizations, substituents in the acycUc precursors can play a major role and cause the sequential reaction to proceed in an unprecedented direction. A particularly striking example is presented in Schone 39. The acycUc precursors differ from those that undergoe the other type of cascade tetracyclization (see above Scheme 33) only by the propargylic methoxy (silyloxy) group, yet yield—under the typical conditions—an unprecedented tetracyclic system, the structure of which has been proved by X-ray analysis. This cascade reaction may involve an unusual -/ hydride elimination as the last step, or an unprecedented dehydrobromination on an alkylpalladium bromide intermediate to yield a palladiumcarbene species that subsequently undergoes an intramolecular cheletropic addition across the distal double bond to yield the cyclopropane ring. 

Notably, Rieke manganese is able to take part in oxidative addition even where Rieke zinc or Rieke magnesium is insufficiently reactive [258]. The 3-thienylmanganese bromide intermediate 123 can be coupled effectively with both aryl iodides and aroyl chlorides via palladium catalysis to give the products 124 and 125 in moderate to high yields (Scheme 50, Table 28) [343, 344],... 

---