Dienes stereospecificity

Phosphorus-containing allyltitanium(IV) complexes, like (129), have been studied as well. - The synthetic importance of their addition products to aldehydes lies on their ready deoxygenation to afford dienes stereospecifically (equation 50). 

Modified method of the diatomic complexes in molecules , which provides a satisfactory prediction of the valent-bound atoms interaction at the stages of chemical adsorption of catalytic system components and monomer molecules, reactions of initiation and chain growth in a-olefins, and 1,3-dienes stereospecific polymerisation reactions. 

P-Napthalenesulfonic acid N-Condensed heterocyclics from 5-alkoxyhydantoins and 1,3-dienes Stereospecific ring closure... 

Dihydro-2H-l,2-oxazines from 1,1-nitrosohalides and dienes Stereospecific ring closure and synthesis... 

The elimination of allylic sulphoxides to give (f jf )- ,3-dienes stereospecifically has been demonstrated by the synthesis of the pheromone of the codling moth (197) (Scheme 28), and the use of a stannyl group rather than silicon as a... 

Palladium(n) chloride reacts with the diene isomers of hexa-2,4-diene stereospecifically to give a pair of epimeric diastereomers as outlined in Scheme 7. Treatment of these allyl compounds with excess of a co-ordinating ligand such as dimethyl sulphoxide, triphenylphosphine, or lithium bromide leads to the initial dienes stereospecifically via conversion into a cr-complex followed by a j5-elimination. The two diastereomers (9) and (10) epimerize in... 

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

Migration of a hydride ligand from Pd to a coordinated alkene (insertion of alkene) to form an alkyl ligand (alkylpalladium complex) (12) is a typical example of the a, /(-insertion of alkenes. In addition, many other un.saturated bonds such as in conjugated dienes, alkynes, CO2, and carbonyl groups, undergo the q, /(-insertion to Pd-X cr-bonds. The insertion of an internal alkyne to the Pd—C bond to form 13 can be understood as the c -carbopa-lladation of the alkyne. The insertion of butadiene into a Ph—Pd bond leads to the rr-allylpalladium complex 14. The insertion is usually highly stereospecific. 

The stereospecific synthesis of an A ring synthon of la-hydroxy vitamin D has been carried out. The ( )-allcene is cyclized to give the (E -c.xo-diene 155, and the (Z)-allcene affords the (Z)-e,xo-diene 156 stereospecifically[125,126]. These results can be understood by the cis addition and syn elimination mechanism. 

Aryl halides react with a wide variety of aryl-, alkenyl- and alkylstan-nanes[548-550]. Coupling of an aryl tritlate with an arylstannane is a good preparative method for diaryls such as 688. The coupling of alkenylstannanes with alkenyl halides proceeds stereospecifically to give conjugated dienes 689. The allylstannane 690 is used for allylation[397,546,551-553]. Aryl and enol triflates react with organostannanes smoothly in the presence of LiCl[554]. 

Section 10 12 Conjugate addition of an alkene (the dienophile) to a conjugated diene gives a cyclohexene derivative in a process called the Diels-Alder reaction It is concerted and stereospecific substituents that are cis to each other on the dienophile remain cis m the product... 

The methiodide of 2,5-dihydrothiophene (239) is transformed in high yield to Z)-l-(methylthio)buta-l,3-diene (240) on treatment with alkali (81AJC1017). The thermal cheletropic extrusion of sulfur dioxide from both cis and trans isomers of 2,5-dihy-drothiophene 1,1-dioxides is highly stereospecific. For example, c/5-2,5-dimethyl-2,5-dihydrothiophene 1,1-dioxide (241) yields ( , )-hexa-2,4-diene (242) and sulfur dioxide (75JA3666, 75JA3673). 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

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). 

Mechanistically the observed stereospecificity can be rationalized by a concerted, pericyclic reaction. In a one-step cycloaddition reaction the dienophile 8 adds 1,4 to the diene 7 via a six-membered cyclic, aromatic transition state 9, where three r-bonds are broken and one jr- and two cr-bonds are formed. The arrangement of the substituents relative to each other at the stereogenic centers of the reactants is retained in the product 10, as a result of the stereospecific y -addition. 

The rearrangement proceeds from the Si-state of the 1,4-diene 1. The Ti-state would allow for different reactions like double bond isomerization. Rigid systems like cyclic dienes, where EfZ -isomerization of a double bond is hindered for steric reasons, can react through the Ti-state. When the rearrangement proceeds from the Si-state, it proves to be stereospecific at C-1 and C-5 no -isomerization is observed. Z-l,l-Diphenyl-3,3-dimethyl-l,4-hexadiene 5 rearranges to the Z-configured vinylcyclopropane 6. In this case the reaction also is regiospecific. Only the vinylcyclopropane 6 is formed, but not the alternative product 7. ... 

Another reaction unique to conjugated dienes is the Diels-Alder cycloaddition. Conjugated dienes react with electron-poor aikenes (dienophiles) in a single step through a cyclic transition slate to yield a cyclohexene product. The reaction is stereospecific, meaning that only a single product stereoisomer is formed, and can occur only if the diene is able to adopt an s-cis conformation. 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

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... 

N-Aminobenzoxazolin-2-one (4), which was readily prepared by animation of benzoxazolin-2-one with hydroxylamine-O-sulfonic acid, is also a useful nitrene precursor (Scheme 2.2). Oxidation of 4 with lead(iv) acetate in the presence of a conjugated diene resulted in exclusive 1,2-addition of nitrene 5, to yield vinylazir-idine (6) in 71 % yield [6]. The formation of vinylaziridines through 1,2-additions of methoxycarbonylnitrene (2) or amino nitrene 5 contrasts with the claimed 1,4-ad-dition of nitrene itself to butadiene [7]. Since the reaction proceeded stereospecif-ically even at high dilution, the nitrene 5 appears to be generated in a resonance-stabilized singlet state, which is probably the ground state [8]. 

Compounds 1, which bear in X an electrofugical leaving group, such as trialkylsilyl or diphenylphosphinyl, are of high value for the synthesis of stereochemically homogeneous 1,3-dienes via stereospecific anti or urn elimination. 

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. 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

To generate molecular libraries, a series of 5-oxo-2-azabicyclo[2.2.2]octane and triaza analogs were prepared via a stereospecific Diels-Alder reaction by reacting Wang-resin-bound diene 35 with a variety of dienophiles [28]. After removing the solid support with a strong acid, adducts 36 were isolated examples of reactions that have furnished the best yields are reported in Scheme 4.6. 

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