Diastereomeric dienes

When trienes with two diastereotopic C-C double bonds are subjected to RCM, two diastereomeric dienes can be formed. Few examples of such reactions have been reported [886,887]. Interestingly, the stereochemical outcome of such cyclizations can be controlled by the choice of the catalyst (Entries 8 and 9, Table 3.19). 

Base-promoted 1,4-dehydrochlorination of 3-(l-chloroethyl)indene leads to a pair of diastereomeric dienes (equation 10.82). How could compounds 56 and 57 be used to determine whether the reaction occurs by a syn or an anti pathway ... 

Sol 6. Thermal isomerization of the substituted dienes takes place through the formation of the cyclobutene intermediate by a thermally allowed con-rotatory electrocycUzation. Under thermal conditions, for a 4n 7u-electron system, ring opening also occurs by conrotatory process. As the two groups are the same there is no selection, and hence the ring opens up by both the conrotatory paths, leading to the formation of two diastereomeric dienes i.e., (2E,4E)- and (2Z,4Z)-butadiene derivatives. (2Z,4 )-Butadiene derivative can be formed only by disrotatory process, which is disallowed under thermal conditions. 

The Diels-Alder reaction of a diene with a substituted olefinic dienophile, e.g. 2, 4, 8, or 12, can go through two geometrically different transition states. With a diene that bears a substituent as a stereochemical marker (any substituent other than hydrogen deuterium will suffice ) at C-1 (e.g. 11a) or substituents at C-1 and C-4 (e.g. 5, 6, 7), the two different transition states lead to diastereomeric products, which differ in the relative configuration at the stereogenic centers connected by the newly formed cr-bonds. The respective transition state as well as the resulting product is termed with the prefix endo or exo. For example, when cyclopentadiene 5 is treated with acrylic acid 15, the cw fo-product 16 and the exo-product 17 can be formed. Formation of the cw fo-product 16 is kinetically favored by secondary orbital interactions (endo rule or Alder rule) Under kinetically controlled conditions it is the major product, and the thermodynamically more stable cxo-product 17 is formed in minor amounts only. 

A key transformation in Corey s prostaglandin synthesis is a Diels-Alder reaction between a 5-(alkoxymethyl)-l,3-cyclopenta-diene and a ketene equivalent such as 2-chloroacrylonitrile (16). As we have already witnessed in Scheme 3, it is possible to bring about a smooth [4+2] cycloaddition reaction between 5-substituted cyclopentadiene 15 and 2-chloroacrylonitrile (16) to give racemic 14 as a mixture of epimeric chloronitriles. Under these conditions, the diastereomeric chloronitriles are both produced in racemic form because one enantiotopic face of dienophile 16 will participate in a Diels-Alder reaction with the same facility as the other enantiotopic face. In subsequent work, Corey s group demonstrated that racemic hydroxy acid 11, derived in three steps from racemic 14 (see Scheme 3), could be resolved in a classical fashion with (+)-ephe-... 

In the third sequence, the diastereomer with a /i-epoxide at the C2-C3 site was targeted (compound 1, Scheme 6). As we have seen, intermediate 11 is not a viable starting substrate to achieve this objective because it rests comfortably in a conformation that enforces a peripheral attack by an oxidant to give the undesired C2-C3 epoxide (Scheme 4). If, on the other hand, the exocyclic methylene at C-5 was to be introduced before the oxidation reaction, then given the known preference for an s-trans diene conformation, conformer 18a (Scheme 6) would be more populated at equilibrium. The A2 3 olefin diastereoface that is interior and hindered in the context of 18b is exterior and accessible in 18a. Subjection of intermediate 11 to the established three-step olefination sequence gives intermediate 18 in 54% overall yield. On the basis of the rationale put forth above, 18 should exist mainly in conformation 18a. Selective epoxidation of the C2-C3 enone double bond with potassium tm-butylperoxide furnishes a 4 1 mixture of diastereomeric epoxides favoring the desired isomer 19 19 arises from a peripheral attack on the enone double bond by er/-butylper-oxide, and it is easily purified by crystallization. A second peripheral attack on the ketone function of 19 by dimethylsulfonium methylide gives intermediate 20 exclusively, in a yield of 69%. 

The cycloaddition of chiral, racemic and non-racemic alkoxybutadienes 109 with phenyltriazolinedione led to aza compounds [110] in high yield, with good facial selectivity (diastereomeric excess 87-92%) (Equation 2.31). The cycloadditions of the same dienes with N-phenylmaleimide require Lewis acid catalysis. 

The diene core does not necessarily need to remain intact, but can rather be cleaved to enable further functionalization. Taking advantage of the diastereomeric s vitch , such a strategy was implemented together with a ring closing metathesis step in the total synthesis of undecenolides like cladospolide [258,259]. 

In this context, also mentionable are several publications by the groups of Dlaz-de-Villegas [242], Guarna [243], Kunz [244] and Waldmann [245], which describe the formation of six-membered azaheterocycles via treatment of an imine with an appropriate substituted diene. For instance, as described by Waldmann and coworkers, reaction of the enantiopure amino acid-derived imines 2-452 with Danishefsky s diene 2-453 in the presence of equimolar amounts of a Lewis acid provided diastereomeric enaminones 2-456 and 2-457 (Scheme 2.105) [245a]. 

As described previously, the Co-mediated carbonylahve Co-cydization of an alkyne and an alkene, is a very powerful procedure in the preparation of cyclopen-tenones [268], However, depending on the reaction conditions it also allows the preparation of 1,3-dienes, which may be intercepted by a Diels-Alder reaction, as described by Carretero and coworkers [285]. As expected, reaction of 6/4-28 with Co2(CO)8 in refluxing acetonitrile led exclusively to the diastereomeric cyclopen-tenones 6/4-29 and 6/4-30 as a 59 41 mixture. However, using trimethylamine-N-... 

On a capillary GC analysis, the separation of positional isomers of epoxy compounds is generally well accomplished by a high polar column, such as DB-23, rather than by a low polar column, such as DB-1. For the positional isomers, a different elution order depending on the kinds of column has not been reported. In the case of two mono epoxides derived from Z6,Z9-dienes, 6,7-epoxides elute slightly faster than 9,10-epoxides [72,170],but the separation is insufficient even on the high polar column. Three monoepoxides derived from Z3,Z6,Z9-trienes elute in the order of 6,7-, 3,4-, and 9,10-epoxides [9]. The former two isomers are sufficiently separated on the high polar column, while the elution of the latter two isomers overlaps [71]. For each positional isomer of diepoxides derived from the Z3,Z6,Z9-trienes, two diastereomeric... 

Compound 316 contains two suitable ene-diene functions that yielded two diastereomeric tetrahydrobenzo[4]qui-nolizidines in quantitative yield and in a 8 92 ratio in a TiCU-catalyzed intramolecular Diels-Alder (IMDA) reaction (Equation 9) <1998T9529>. 

Palladium oxazoline compounds (e.g., (47)) have been used to catalyze the cyclization/hydro-silylation of functionalized 1,6-dienes (Scheme 31). With R = Pr1, >95% diastereomeric excess and 87% ee was achieved at low temperature. Changing the ligand bulk with R = Bu1 gave a higher ee value, but poorer diastereoselectivity. A range of functional groups can be tolerated at both the allylic and terminal alkene positions.135-137... 

The substitution of the exo-methylene hydrogen atoms of MCP with halogens seems to favor the [2 + 2] cycloaddition reaction by stabilizing the intermediate diradical. Indeed, chloromethylenecyclopropane (96) reacts with acrylonitrile (519) to give a diastereomeric mixture of spirohexanes in good yield (Table 41, entry 2) [27], but was unreactive towards styrene and ds-stilbene. Anyway, it reacted with dienes (2,3-dimethylbutadiene, cyclopentadiene, cyc-lohexadiene, furan) exclusively in a [4 + 2] fashion (see Sect. 2.1.1) [27], while its... 

Diastereomerically pure diene 89 (R=SiMe2tBu) was assembled in a straightforward manner starting from cycloheptene 90 (Scheme 28). It is not surprising to find that this particular substrate fails to cyclize when reacted with Id under standard high dilution conditions. 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Dimers with a 1,2-bismethylenecyclobutane structure were obtained from 585 [240], 590 [238], 591 [241], 592 [242], 593 [243] and from the pinene derivative 597 [244]. The interception of 592 by 1,3-diphenylisobenzofuran (DPIBF) afforded two diastereomeric [4+ 2]-cycloadducts [245], Bicyclo[5.1.0]octa-3,4-diene (594) was generated by /3-elimination and trapped by sodium pyrrolidide because of the question of the extent to which the corresponding bicyclooctyne is formed in addition to 594 [184], Liberated by /3-elimination from ll,ll-dichloro-l,6-methano[10]annulene in... 

Another example of a diene undergoing a [2 + 2] cycloaddition reaction with an alkene has been reported recently4. 2-Dimethylaluminumoxy-l,3-cyclohexadiene (7) reacted with phenyl vinyl sulfoxide (8) to afford a diastereomeric mixture of cis substituted cyclobutanols 9 (equation 3). The occurrence of a [2 + 2] cycloaddition as well as the high cis stereoselectivity observed were explained by a pre-organization of the reactants by complexation of the diene bound aluminum with the sulfoxide oxygen on the olefin. 

Acylnitroso compounds 197 (R = Me, Ph or Bn) react in situ with 1-methoxycarbonyl-1,2-dihydropyridine to yield solely the bridged adducts 198 quantitatively. On the other hand, 1 1 mixtures of the regioisomers 199 and 200 were formed from the nitroso-formates 187 (R = Me or Bn) (equation 110)103. The chiral acylnitroso compounds 201 and 202, which are of opposite helicity, add to cyclohexadiene to give optically active dihydrooxazines in greater than 98% diastereomeric excess (equations 111 and 112)104. Similarly, periodate oxidation of the optically active hydroxamic acid 203 in the presence of cyclopentadiene, cyclohexa-1,3-diene and cyclohepta-1,3-diene affords chiral products 204 (n = 1, 2 and 3, respectively) in 70-88% yields and 87-98% de (equation 113)105. 

Chiral dienes or chiral dienophiles or chiral Lewis acid catalysts may be involved in cycloaddition reactions. When any two of these are combined double asymmetric induction operates111. Thus the chiral diene 223 and the optically active dienophile 224 (from D-mandelic acid) gave 225 in high de values, whereas the same diene and the enantiomeric dienophile 226 (from L-mandelic acid) — a mismatched pair—formed the diastereomeric cycloadduct 227 in only 4% de (equation 121)112. 

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