1,3-Dienes stereoselective synthesis

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of... 

Based on the facile formation and reactivity of323, and the retro Diels-Alder reaction of 325306,310, a simple procedure has been developed for the stereoselective synthesis of functionalized conjugated dienes as well as vinylallenes311 (see equation 119). 

Watt and Drummond, were considered to be inert for C-C bond forming reactions. However, by the expedient of transmetallation to Cu, Ni, Zn, Li, and Al, methodologies for the stereoselective synthesis of olefins and dienes, as well as unusual heterocycles, aromatics and their ring-annulated products are now available which are beginning to make impact on material science, e. g. synthesis of pentacenes and polyphenylenes. Takahashi and Li provide evidence that, with further developments in transmetallation and handling the zirconacycles outside of the Schlenk tube techniques, synthetic utility will increase and new catalytic reactions will be developed. 

Considering the monoaminomercuration-demercuration of 1,4-hexadiene with /V-me-thylaniline leads to V-methyl-lV-(l-methylpent-3-enyl)aniline, the stereoselective synthesis of /V-alkoxycarbonyl or /V-tosyl s-2,5-dimethylpyrrolidine from the same diene has been explained172 on the basis of an initial amidomercuration reaction on the terminal bond followed by the second addition of mercury(II) salt to the internal double bond, on the less sterically hindered site (equation 171). 

Complex hydrides have been used rather frequently for the conjugate reduction of activated dienes92-95. Just and coworkers92 found that the reduction of a,ft-unsaturated ketene 5,5-acetals with lithium triethylborohydride provided mixtures of 1,4- and 1,6-reduction products which were transformed into enals by treatment with mercuric salts (equation 27). Likewise, tetrahydro-3//-naphthalen-2-ones can be reduced with L-Selectride to the 1,6-reduction products93 -95 this reaction has been utilized in the stereoselective synthesis of several terpenes, e.g. of (/ )-(—)-ligularenolide (equation 28)95. Other methods for the conjugate reduction of acceptor-substituted dienes involve the use of methylcopper/diisobutylaluminum hydride96 and of the Hantzsch ester... 

The Wittig reaction was employed to fuse diene 49 and aldehyde 50, in the final stages of the stereoselective synthesis of epothilone B, a macrocyclic compound with potential antifungal properties (equation 31)49. 

Michael additions of organocopper reagents to acceptor-substituted dienes have found widespread application in target-oriented stereoselective synthesis [12]. For... 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

A concise stereoselective synthesis of a myoinositol derivative has been achieved by ring-closing metathesis of diene 21 prepared from a readily available bis-Weinreb amide 20 of D-tartrate [Eq. (6.19)]. ... 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

Oxy-Cope rearrangement (7, 302-303 8, 412-414). Further studies indicate that the rearrangement of 1,5-diene alkoxides can be used for stereoselective generation of asymmetry. An application is the stereoselective synthesis of eryf/iro-juvabione (1), a sesquiterpene from Abies balsamea, shown in equation (I). ... 

Stereoselective synthesis of 1,4-dienes This Pd complex markedly catalyzes the cross-coupling of alkenyl and aryl metals containing Al, Zr, or Zn with allylic halides, but not of alkyl metals. The coupling is markedly stereo- and regioseleclive. Examples ... 

Enantiomerically pure pipecolic acid (6) is accessible essentially by two well-established synthetic routes (i) cyclization of l- or D-lysine by reaction with disodium nitrosyl-pentacyanoferrate(II) with preservation of configuration at C2 215 216 (ii) ring closure of A ,Ae-bis(A-nitroso-A-tosyl) derivatives of l- or D-lysine, again with retention of chirality at C2. 217 Stereoselective synthesis of pipecolic acid derivatives, substituted in position 4, is achieved using the aza-Diels-Alder reaction of imines with dienes 218-220 or via an ene-iminium cyclization. 221 222 ... 

Many uses of the sulfolene reaction for synthetic purposes are associated with this easy stereoselective synthesis of conjugated dienes [109, 203]. The development of this methodology led to new routes for the introduction of electrophiles in the 2 and (or) 5 positions of the sulfolenes... 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

Several recent reviews have included specific types of electrophilic cyclofunctionalization reactions.1 Important areas covered in these reviews are halolactonization u cyclofunctionalization of unsaturated hydroxy compounds to form tetrahydrofurans and tetrahydropyrans lb cyclofunctionalization of unsaturated amino compounds lc cyclofunctionalization of unsaturated sulfur and phosphorus compounds ld lf electrophilic heterocyclization of unconjugated dienes 1 synthesis of y-butyrolactones 1 h synthesis of functionalized dihydro- and tetrahydro-furans lj cyclofunctionalization using selenium reagents lk lm stereocontrol in synthesis of acyclic systems 1" stereoselectivity in cyclofunctionalizations lP and cyclofunctionalizations in the synthesis of a-methylenelactones.lq Previous reference works have also addressed this topic.2... 

Since the oxidative addition occurs with retention of configuration and the transmetallation is also stereospecific with retention, the method is extremely valuable for the stereoselective synthesis of conjugated dienes. The... 

A new protocol for the stereoselective synthesis of (i-lactams [213] has been reported to be performed by a conrotatory ring closure of l-halo-3-aza-4-alkyl-l, 3-dienes, previously prepared by Staudinger methodology, (for the synthesis and chemistry of /V-silyl imines see [214] for [2+2] cycloaddition of /V-silyl imines and ketenes see [215]) in refluxing toluene (Scheme 96). 

Scheme 96 Stereoselective synthesis of 3-unsubstituted P-lactams by conrotatory ring closure of 1,3-diene derivatives...

The coupling of alkenylboranes with alkenyl halides is particularly useful in the stereoselective synthesis of 1,3-diene systems of four possible double-bond isomers... 

The stereoselective synthesis of 1,4-disubstituted-l,3-dienes proceeds by head-to-head oxidative coupling of two alkynes with formation of an isolable metallacyclic biscarbene ruthenium complex [23], as shown in Scheme 6. Several key experiments involving labeled reagents and stoichiometric reactions and theoretical studies support the formation of a mixed Fischer-Schrock-type biscarbene complex which undergoes protonation at one carbene carbon atom whereas the other becomes accessible to nucleophilic addition of the carboxylate anion (Scheme 6) [23]. 

Svatos, A. and Saman, D. (1997). Efficient stereoselective synthesis of all geometrical isomers of heptadeca-11,13-dienes. Collect. Czech. Chem. Commun., 62,... 

Fig. 16.20. Alkenylation of isomeric alkenylboronic acid esters with isomeric iodo-alkenes stereoselective synthesis of isomeric 1,3-dienes.

In reactions of alkenyl triflates with stereogenic C=C double bonds, coupling reactions of these kinds convert the Csp2—X bond of the alkenyl triflate into the Csp2—C bond of the substitution product with complete retention of configuration. The stereoselective synthesis of a 1,3-diene from an alkenyl triflate and (vinyl)2CuLi provides an example (Figure 13.1). 

The more recent work on this area deals predominantly with the asymmetric induction in aza Diels-Alder reactions in order to develop a novel powerful tool for the stereoselective synthesis of biologically active compounds. Thus, Wald-mann et al. demonstrated the utility of chiral imines derived from enantiopure amino acids by obtaining the cycloadduct 3-3 in very good diastereoselectivity from imine 3-1 and Brassard s diene 3-2 (Fig. 3-1) [181]. 

An excellent, general procedure for the stereoselective synthesis of conjugated 13,13 dienes utilizes 1-halo-l-alkynes and thexylborane (36). We prepared the compound XXXX (which is the 13,13 isomer of the Lobesia botrana pheromone XXIX) in >98% stereochemical purity by this procedure (Figure 19). 

In this tandem allylic C-H bond activation, followed by an elimination reaction, substituted l-zircono-lZ,3 -dienes (zirconium moiety at the terminal position of the dienyl system) were easily prepared as unique isomers. With the idea of extending this methodology to the stereoselective synthesis of 3-zircono-1,3-diene (zirconium moiety at the internal position of the dienyl system), 119 was prepared and the reactivity was investigated with (1-butene)ZrCp2 21 (119 was obtained by carbocupration of the a-allyl alkoxy-allene, Scheme 35) [79]. When 119 was submitted to the tandem reaction, the diene 120 was isolated after hydrolysis as a unique ( ,Z) isomer in 75% isolated yield (Scheme 44). 

Alkenylboron compounds couple with the representative organic halides or triflates (Scheme 28). Hexaalkylbenzene was synthesized by sixfold alkenylation (55) of hexabromobenzene followed by catalytic hydrogenation of the double bonds 11521. The reaction of 1-alkenylborane with 1-bromo-l-alkyne stereose-lectively provided ( )-enyne (56) which was then converted into ( ,Z)-hexa-deca-10,12-dienal, a sex pheromone of the melonworm 11531. Due to the difficulty of purification of a geometrical mixture, the stereoselective synthesis is critical for such dienes or trienes. The PGEi derivatives (57) were synthesized... 

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