Stereospecific reactions diene synthesis

Scheme 8 presents the sequence of reactions that led to the synthesis of the B-ring of vitamin B12 by the Eschenmoser group. An important virtue of the Diels-Alder reaction is that it is a stereospecific process wherein relative stereochemical relationships present in the diene and/or the dienophile are preserved throughout the course of the reaction.8 Thus, when the doubly activated dienophile 12 (Scheme 8) is exposed to butadiene 11 in the presence of stannic chloride, a stereospecific reaction takes place to give compound 27 in racemic form. As expected, the trans relationship between... 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

The Diels-Alder reaction is of wide scope. Not all the atoms involved in ring formation have to be carbon atoms the hetero-Diels-Alder reaction involving one or more heteroatom centers can be used for the synthesis of six-membered heterocycles. The reverse of the Diels-Alder reaction—the retro-Diels-Alder reaction —also is of interest as a synthetic method. Moreover and most importantly the usefulness of the Diels-Alder reaction is based on its yyn-stereospecificity, with respect to the dienophile as well as the diene, and its predictable regio-and enrfo-selectivities. °... 

Vinyl chlorides. In the presence of Ni[P(CAH5)3]4 (6, 570)5 Grignard reagents reacts stereospecifically with (E)- or (Z)-dichloroethylene to form (E)- or (Z)-l-chloro-alkencs, respectively. The reaction has been used for an efficient synthesis of the 1,3-diene 1. the sex pheromone of Lobesia botrane (equation 1). 

In a similar manner, alkynes can undergo sequential carbometallation reactions, previously illustrated in equation (32).136 It is possible to combine carbocupration of alkynes with the use of a Michael acceptor as electrophile when that electrophile is a vinylphosphonium salt, carbocupration can be coupled to Wittig alkenation to result in a stereospecific synthesis of dienes via a one-pot, four-component, four carbon-carbon bond-forming reaction sequence.302... 

Indirect methods, which are primarily essentially of academic interest, nevertheless may find use under special circumstances. One of these, involving the brominative decarboxylation (Borodin-Huns-diecker reaction) of silver a-fluorocyclopropanecarboxylate, provides a convenient and stereospecific route to the synthesis of fluorobromocyclopropyl compounds (equation 26).96 Another approach makes use of the Diels-Alder reaction between tetrachlorocyclopropene and dienes (equation 27).97,98 The adducts can undergo facile dehydrohalogenation or ring opening. 

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