Prenyl bromide

Tabushi et al. (1979) have shown that p-cyclodextrin in aqueous alkaline solution allows highly selective one-step synthesis of vitamin Kj (or K2) analogues here the key step is alkylation of 2-methyl hydronaphthoquinone with allyl, crotyl, methallyl, or prenyl bromide. 

In the synthetic procedure, verbenone 118, the air oxidation product of pinene, is first treated with t-BuOK. followed by the addition of prenyl bromide to give a C-ll alkylated product. Selective ozonolysis of the more electron-rich double bond provides the aldehyde 119 with 85% yield. The A ring of taxane is then created through photorearrangement of the aldehyde 119, yielding the chrysanthenone derivative 120 (85% yield, over 94% ee). 

Allyl tosylate is also an excellent reactant (entry 2, Table 5.8), while allyl acetate is not under Cu(I)-catalyzed conditions. Not only saturated acylzirconocene chlorides, but also a,(3-unsaturated acylzirconocene chlorides give coupling products in good yields (entry 8, Table 5.8). Prenyl bromide also reacts with acylzirconocene chlorides under identical conditions to give a mixture of regioisomers (Scheme 5.30). However, a longer reaction time (10 h) is required for the completion of the reaction as compared to the reaction of allyl bromide (1 h). 

We have chosen epoxy olefin 10 as substrate for our initial examinations for two reasons. Firstly, 10 is synthesized in a straightforward manner from al-lyl diethyl malonate by epoxidation and an Sn2 reaction with prenyl bromide. Secondly, it is known from the work of others [17-20] and ourselves [65, 66,73,74] that compounds similar to 10 cyclize to yield mainly the essential ds-fused radicals with selectivities of about 85 15 to 90 10. 

This reaction was applied to the synthesis of quinonoid natural products [34]. Propargyl bromides 62 a and 62b, which were prepared from prenyl bromide and phytyl bromide by a standard procedure, were converted to the corresponding aluminum reagents by reaction with powdered aluminum and a catalytic amount of mercuric chloride [35]. Then the iodomagnesium salt of cyclopropanol hemiacetal was treated with these reagents [36] affording the prenyl derivative 63 a and the phytyl derivative 63 b in 49 and 50% yield, respectively (Scheme 26). 

Regioselective electrophilic bromination of the carbazole 1025 afforded the 6-bromocarbazole 1026. Cleavage of the methyl ether to 1027 and subsequent nickel-mediated coupling using a dimeric 7i-prenylnickel bromide complex prepared in situ from prenyl bromide 925 and bis(l,5-cyclooctadiene)nickel(0) led directly to siamenol (89) (546) (Scheme 5.151). 

A number of natural flavonoids, coumarins and chromones have a prenyl (3-methylbut-2-enyl) side chain which is capable of cyclization on to an oxygen atom to form a pyran ring (77HC(31)633). Prenylation is effected by reaction with either 3-methylbut-2-enyl (prenyl) bromide or 2-methylbut-3-en-2-ol in the presence of a base or a Lewis acid. When this reaction is applied to flavonoids, the prenyl group has a choice of two benzene rings and... 

The alkylation goes well as 63 is the reactive allylic halide prenyl bromide and hydrolysis and decarboxylation occur as usual.13... 

Heating a variety of phenols with isoprene under pressure in the presence of a zeolite catalyst affords chromans in good yield <1998S301>. Likewise, the synthesis of 2,2-dimethylchromans can be achieved via Montmorillonite K10 clay catalyzed condensation of substituted phenols with prenyl bromide <2004SL2028>. 

Prenyl bromide affords better chemical yields and better enantioselectivities than allyl bromide (Table 6). The best result (99% yield, 90% (R) ee) is obtained when benzaldehyde is treated with prenyl bromide in the presence of (—)-cinchonidine. A similar enantioselective propargylation reaction of aldehydes with enantioselectivity up to 85% has been achieved in organic solvents by using stoichiometric amounts of (—)-cinchonidine as the chiral source (Table 7).190... 

Sometimes this ambiguity is useful. The tertiary allylic alcohol 2-methylbut-3-en-2-ol is easy to prepare and reacts well by the SnI mechanism because it is both tertiary and allylic. The allylic car-bocation intermediate is very unsymmetrical and reacts only at the less substituted end to give prenyl bromide . 

Prenyl bromide is a building block for making the class of natural products known as terpenes and discussed in Chapter 49. we come back to reactions of allyfic compounds in Chapter 23. 

If the add is HBr, then nucleophilic attack by Br on the cation follows. The cation is attacked at the less hindered end to give the important compound prenyl bromide. This is very much the sort of reaction you met in Chapter 17—it is the second half of an S>jl substitution reaction on an allylic compound. 

If the allylic halide is unsymmetrically substituted, we can tell which process occurs and the normal result is that nucleophilic attack occurs at the less hindered end of the allylic system whether that means S 2 or Sn2. This important allylic bromide, known as prenyl bromide , normally reacts entirely via the Sn2 reaction. 

An important example is the reaction of prenyl bromide with phenols. This is simply carried out with K2CO3 in acetone as phenols are acidic enough (pKa 10) to be substantially deprotonated by carbonate. The product is essentially entirely from the S>f2 route, and is used in the Claisen rearrangement (Chapter 36). 

You might ask a very good question at this point. How do we know that these reactions really take place by Sn2 and Sn2 mechanisms and not by an S l mechanism via the stable allyl cation Well in the case of prenyl bromide, we don t In fact, we suspect that the cation probably is an intermediate, because prenyl bromide and its allylic isomer are in rapid equilibrium in solution at room temperature. 

The equilibrium is entirely in favour of prenyl bromide because of its more highly substituted double bond. Reactions on the tertiary allylic isomer are very likely to take place by the S l mechanism the cation is stable because it is tertiary and allylic and the equilibration tells us it is already there. Even if the reactions were bimolecular, no mechanism would be necessary for the tertiary... 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

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