Dienes reagents

Another interesting development is the use of fluorous-based scavengers in conjunction with microwave synthesis and fluorous solid-phase extraction (F-SPE) for purification. This was recently illustrated by Werner and Curran [74] in their investigation of the Diels-Alder cycloaddition of maleic anhydride to diphenylbutadiene (Scheme 11.23). After performing microwave-assisted cycloaddition (160 °C, 10 min) with a 50% excess of the diene, the excess diene reagent was scavenged by a structurally related maleimide fluorous dienophile under the same reaction conditions. Elution of the product mixture from an F-SPE column with Me0H-H20 provided the desired cycloadduct 89 in 79% yield and 90% purity. Subsequent elution with diethyl ether furnished the fluorous Diels-Alder cycloadduct. 

The Diels-Alder Reaction consists in the direct combination of a compound containing a conjugated diene system u ith a reagent which possesses a double or triple bond activated bj suitable adjacent groups. Examples of such reagents are maleic anhydride, p-benzoquinone, acraldehyde and acetylene dicarboxylic esters. Combination always occurs at the 1,4 positions of the diene system ... 

Now consider strategy b. How would you make the diene acid B, what reagent would you use for the carbene synthon, and how do you rate the chances of this route ... 

Comments We have to explore new chemistry here and the main problem does seem to be getting fire right combination of diene and carbene reagent. Perhaps not such a good route. 

In view of the synthetic importance of dicarbonvl compounds surprisingly little has been done, apart from carotene synthesis, on dialkenylation with Wittig reagents. However, from the few examples reported one may conclude, that no special problems are involved. Benzocyclobutanedione was converted by two equivalents of methoxycarbonylmethylidenetri-phenylphosphorane to the corresponding diene in 85% yield (M. P. Cava, 1960). 

The alkenylzirconium 685, prepared by hydrozirconation of a terminal alkyne with hydrozirconocene chloride, reacts with alkenyl halide to afford the conjugated diene 686(545]. The Zr reagent can be used even in the presence of the carbonyl group in 687, which is sensitive to Al and Mg reagents. 

It was claimed that the Z-form of the allylic acetate 430 was retained in homoallylic ketone 431 obtained by reaction with the potassium enolate of 3-vinylcyclopentanone (429), after treatment with triethylborane[282]. Usually this is not possible. The reaction of a (Z)-allylic chloride with an alkenylaluminum reagent to give 1,4-dienes proceeds with retention of the stereochemistry to a considerable extent when it is carried out at -70 C[283]. 

Benzyne is a reactive dienophile and gives Diels-Alder products when generated m the presence of dienes In these cases it is convenient to form benzyne by dissociation of the Grignard reagent of o bromofluoro benzene... 

Addition (Section 6 1) Reaction in which a reagent X—Y adds to a multiple bond so that X becomes attached to one of the carbons of the multiple bond and Y to the other 1 2 Addition (Section 10 10) Addition of reagents of the type X—Y to conjugated dienes in which X and Y add to adja cent doubly bonded carbons... 

Addition (Section 10 10) Addition of reagents of the type X—Y to conjugated dienes in which X and Y add to the ter mini of the diene system... 

Conjugate acid (Section 1 13) The species formed from a Brpnsted base after it has accepted a proton Conjugate addition (Sections 1010 and 1812) Addition reaction in which the reagent adds to the termini of the con jugated system with migration of the double bond synony mous with 1 4 addition The most common examples include conjugate addition to 1 3 dienes and to a 3 unsaturated car bonyl compounds... 

The organoborate intermediates can also be generated from alkenylboronic esters and alkyllithium or Grignard reagents, or from ttialkylboranes and alkenyllithium compounds. Conjugated symmetrical and unsymmetrical diynes (289—291), stereochemically pure 1,3-dienes (292,293), and 1,3-enynes (294) including functionali2ed systems can be prepared (289,295). 

A catalyst, usually acid, is required to promote chemoselective and regioselective reduction under mild conditions. A variety of organosilanes can be used, but triethylsilane ia the presence of trifiuoroacetic acid is the most frequendy reported. Use of this reagent enables reduction of alkenes to alkanes. Branched alkenes are reduced more readily than unbranched ones. Selective hydrogenation of branched dienes is also possible. 

Reaction of pyridazine 1-oxide with phenylmagnesium bromide gives 1,4-diphenyl-butadiene as the main product and l-phenylbut-l-en-3-yne and 3,6-diphenylpyridazine as by-products, while alkyl Grignard reagents lead to the corresponding 1,3-dienes exclusively (79JCS(P1)2136>. 

This procedure illustrates a general method for the preparation of 2-hydroxybicyclo[3.2.0]heptanes by copper(I)-catalyzed photobicyclization of 3-hydroxy-1,6-heptadienes, and a general route to the requisite dienes from allyl alcohols by conversion to 4-pentenals and treatment of the latter with vinyl Grignard reagents. 

The double bond transposition could also be achieved by the conversion of an intermediate for PGA2 synthesis into a 1,3-diene iron tricarbonyl complex from which PGC2 was synthesized in four steps. The Fe(CO)3 diene complex which survived the Wittig reaction was cleanly removed by Collins reagent in the subsequent step (Ref. 10). 

A solution of 17-cyanoandrosta-5,16-dien-3jS-ol acetate (46 g) and anhydrous potassium acetate (0.46 g) in methylene dichloride (310 ml) is treated with a mixture of 40% peracetic acid (37 ml) and anhydrous potassium acetate (1.84 g) in methylene dichloride (46 ml), the temperature of the solution being maintained below 25°. The mixture is stored at room temperature for 4 hr and then washed successively with water, 5% sodium bicarbonate solution (aqueous sodium bisulfite, 10g/150g water, has been used to decompose excess reagent before workup) and water until neutral. Evaporation of the dried solution and addition of ether gives 24.1 g of 5oc,6a-epoxy-17-cyanoandrost-16-en-3 -ol acetate mp 187-190°. One recrystallization from methanol gives 20.4 g of oxirane melting at 191-194°. 

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