Synthesis Shapiro reaction

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

An elegant application of the catalytic Shapiro reaction has been found in the synthesis of the natural product 129 (equation 45), a component of the sex pheromone of the summer fruit tortrix moth (Adoxophyes orana). ... 

A complementary approach, developed by Paquette, - uses substituted acryloyl chlorides as addends in reaction with structii ly embellished vinylsilanes. A general route to the vinylsilanes (87) was found in the silylation of vinyllithiums generated by the Shapiro reaction.The acylation with acryloyl chlorides takes place readily with aluminum trichloride to afford the divinyl ketones which are subsequently cyclized with tin tetrachloride. The Nazarov cyclization products were formed as a mixture of double tend isomers (equation 47). The best results were obtained with p,p-dimethylacryloyl chloride. Crotonyl chloride could be employed, but acryloyl chloride proved impractical. This metl owes much of its utility to the regiocontroUed synthesis of Ae vinylsilmes, thereby clearly establishing the loci of cyclopentannulation. 

BAMBERGER Benzotnazine synthesis 17 BAMFORD - STEVENS CAGLIOTI - SHAPIRO Reaction 18 BARBIER Reaction 19 BARBIER - VnlELAND DegradaUon 20 BART SCHEUER Arsonylation 21 BARTON Name photolysis 22 BARTON Deamination 23 BARTON Decarboxylation 24... 

The Bamford-Stevens reaction is the base-catalyzed decomposition of arenesulfonylhydrazones of aldehydes and ketones, leading to the formation of alkenes an or cyclopropanes. There are several important general reviews in this area of organic synthesis. Since the reactions are mostly carried out either in protic or in aprotic solvents, the reaction types are divided into the protic and aprotic Bamford-Stevens processes. This section reviews recent examples in the synthesis of alkenes and cyclopropanes from arenesulfonylhydrazones, which is closely related to the following Shapiro reaction. 

The title reaction represents the decomposition of arenesulfonylhydrazones with alkyllithium reagents to furnish unrearranged, less-substituted alkenes almost exclusively. The in situ generated alkenyllithium reagents can be further elaborated by reaction with an electrophile. Since the electrophile can be easily varied, the Shapiro reaction p>ermits the convenient transformation of a ketone into a single substituted alkene in a synthetically useful way. This section will highlight the versatility of this reaction in selective organic synthesis. 

The original Shapiro reaction involves the preparation of unfiinctionalized alkenes from ketone tosyl-hydrazones by quenching of the in situ generated alkenyllithium reagents with water. Recent applications of this reaction in natural product synthesis include the synthesis of 9(0)-methanoprostacyclin (Scheme 12), the in vitro conversion of humulene to A ( -capnellene (Scheme 13), the synthesis of die basic skeleton of isoadsirene (equation S2) ° and the total synthesis of the eudesmanolides rothin A and rothin B (equation 53). ... 

Reactive alkenyl anions prepared by the Shapiro reaction from trisylhydrazones of polyenones and their smooth 1,2-addition to polyenals provides a new route to the versatile synthesis of hydroxymethyl-... 

The synthon of the a-acrylate anion is available from a secondary a-keto carboxamide by the Shapiro reaction. The secondary a-ketoamide trisylhydrazones ate ptepar in a one-pot synthesis by reaction of the isocyanides with acid chloride, water and trisylhydrazine in sequence. In DME solvent, the hydra-zone (103) is smoothly metallated with BuLi to give Ae trianion (KH). Allylation of the trianion (104) gives the hydrazone (105). Alternatively, warming (104) up to room temperature yields the dianion (106) which can be intercepted with several electrophiles (Scheme 23). The adduct (107) is readily transformed into the rran -iodo lactone (108) stereospecifically (equation 56). This chemistry also has been applied to a new synthesis of -lactams (Scheme 24). ... 

The first enantioselective total synthesis of (-)-myltaylenol was achieved in the laboratory of E. Winterfeldt. The authors used an intramolecular Diels-Alder cycloaddition and the Shapiro reaction as key transformations to construct the unusual carbon framework of this sesquiterpenoid alcohol natural product, which contains three consecutive quaternary carbon atoms. 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

Another fragmentation reaction especially useful for the synthesis of vinyllithium compounds is the well-known Shapiro reaction We were successful in preparing 2,3-dilithio-l,3-butadiene 166 by a double Shapiro reaction although in 12% yield only The main reaction product was 2-butyne. 

The Shapiro reaction has frequently been employed in the construction of complex molecules. A few recent applications of this method to the synthesis of natural products are described below. 

The conversion of ketone 38 to alkene 40 in the context of Winterfeldt s synthesis of (-)-myltaylenol was accomplished in two steps using classical conditions for the Shapiro reaction.22 The tosylhydrazone 39 was generated cleanly from 38 in near quantitative (98%) yield. Treatment of 39 with excess n-BuLi provided 40 in 90% yield. 

The Shapiro reaction has also been employed as a key step in Sorensen s synthesis of (-)-hispidospermidin.24 As shown below, Shapiro reaction of 45 followed by transmetalation to Mg and trapping with pyruvate derivative 46 provided 47 in 55% yield as a single diastereomer. 

Several approaches to the synthesis of taxol and the taxane skeleton have employed Shapiro reactions.25 An interesting route to the taxol A-ring that illustrates the utility of dianion functionalization prior to alkene generation was recently described by Koskinen.256 As shown below, treatment of tosylhydrazone 48 with 2.2 equiv of n-BuLi... 

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