Trans-adducts

Benzene-sensitized photolysis of methyl 3-cyclohexene-1-carboxylate in acetic acid leads to addition of acetic acid to the double bond. Only the trans adducts are formed. What factor(s) is (are) responsible for the reaction stereochemistry Which of the two possible addition products, A or B, do you expect to be the major product ... 

The reaction of 5-methoxy-2(5//)-furanone 168 with amines was also studied (89T6799). The conjugated addition of ethanolamine to the furanone 168 gave the racemic amino lactone 275 (R = CH2CH20H). Similarly, piperazine reacted with two equivalents of 168 to provide the diadduct 276 as a single diastereomer (no traces of the other isomer were detected). With tryptamine, the reaction was nearly quantitative with the the formation the tran -adduct 277 (R = tryptophanyl) (Scheme 72) (89T6799). 

Ethyl l//-azepine-l-carboxylate and chlorotrimethylsilane, in hexamethylphosphoric triamide in the presence of magnesium, followed by quenching into water, yields the 1 2 trans-adduct 3.279 The reaction follows a similar path with dichlorodimethylsilane, whereas with dichloro-diphenylsilane a mixture of the 1 2 adduct 4 and the disiloxane 5 is obtained. 

This 1,2-asymmetric induction has been attributed to stcric and stcrcoclectronic factors. Similarly, the cuprate additions to 4-alkylcyclopentenones l7 -19, and 4-alkylcyclohexcnones16 b-18 proceeded with very high trans diastereoselection. The copper iodide catalyzed addition of propylmagnesium bromide to 4-methyl-2-cyclohexenone gave a trans/cis ratio of 80 20, whereas the addition to 5-methyl-2-cyclohexenone produced a transjcis ratio of 93 72 3-Silyloxy system 3 gave the trans-adduct 4 on treatment with butylcopper-boron trifluoride reagent20. 

This procedure has been applied as a key step in the synthesis of ( + )-ramulosin. Using dimethyl 1,3-propanedioate or cyanoacetate under basic conditions (20 °C, sodium methoxide) trans-adducts are obtained preferentially (diastereomeric ratios 2.5-l0 1)264. 

In contrast cyclic y-(rey/-butyldimethylsilyloxy)-a,/ -unsaturated sulfones undergo addition of organometallic reagents to give mainly trans-adducts after reductive removal of the sulfonyl group. 

Stable cA-1-phenyl-1-cyclohexene 24 photodimeiizes via Diels Alder cycloaddition to trans adduct 25 (Equation 1.33) [66] and the photoexcitation of dihydrobenzofuran-fused cyclohexenone 26 in net furan gives the trans fused Diels-Alder adduct 27 (Equation 1.34) [67]. 

The different ratios of 52/53 produced by cycloadditions performed at atmospheric and high pressure, and the forma tion of the unusual trans adducts 53, have been explained by the facts that (i) Diels-Alder reactions under atmospheric pressure are thermodynamically controlled, and (ii) the anti-endo adducts 52 are converted into the short-lived syn-endo adducts 54 which tautomerize (via a dienol or its aluminum complexes) to 53. The formation of trans compounds 53 by induced post-cycloaddition isomerization makes the method more flexible and therefore more useful in organic synthesis. 

N-Acylnitroso compounds 4 are generated in situ by periodate oxidation of hydroxamic acids 3 and react with 1,3-dienes (e.g. butadiene) to give 1,2-oxazines 5 (Scheme 6.3). The periodate oxidation of 4-O-protected homo-chiral hydroxamic acid 6 occurs in water in heterogeneous phase at 0°C, and the N-acylnitroso compound 7 that is generated immediately cyclizes to cis and tranx-l,2-oxazinolactams (Scheme 6.4) [17a, b]. When the cycloaddition is carried out in CHCI3 solution, the reaction is poorly diastereo-selective. In water, a considerable enhancement in favor of the trans adduct is observed. 

The synthesis turns out to be remarkably easy. The trans adduct cyclises to the strained anhydride (13) on heating with acetyl chloride. 

The same corynoline analog (214) was obtained more conveniently through photolysis in the presence of nitrosobenzene. Addition of nitrosobenzene to 208 from the opposite side of the methyl group resulted in the B/C-trans adduct 215. Reduction of 215 with sodium borohydride followed by acidic treatment gave the B/C-cis product 217 via 216. Hydroxylation of 217 with performic acid and hydrogenolysis of the diol 218 completed the synthesis of 214 (126). 

The a-n interaction in the excited-state n electron systems is also successfully treated. The 1,2-addition will take place with cis mode as is indicated in Fig. 7.39. This was predicated in reference B6>. Experimental evidence 64>149> is the photoinduced addition of IV-chlorourethane to olefins which gives mainly cis addition product, while thermal addition produces a dominantly trans adduct. 

A concerted four-center cis addition leads to (52) and a trans adduct a trans addition, possibly via protonium species, leads to (53) and a cis adduct a stepwise cationic addition leads to (54) and a mixture of cis and trans adducts. Recent studies by Marshall and Wurth strongly indicate that intermediate (54) is correct. Irradiation of octalin (55) in aqueous /-butyl alcohol (DaO)-xylene results in formation of the equatorially deuterated alcohols (56) and (57) and the equatorially deuterated exocyclic olefin (58) ... 

Nitrone 1,3-DC reactions are still the most general approach to isoxazolidines. The stereocontrol is usually achieved by the use of chiral nitrones and/or dipolarophiles, but new interesting achievements on Lewis acid catalyzed cycloadditions are also frequently reported. Tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanatedionate) europium(III) [Eu(fod)3] selectively activated the Z-isomer of C-alkoxycarbonyl nitrone 75 existing as an E,Z-equilibrium mixture by forming the (Z)-75-Eu(fod)3 complex. (Z)-75-Eu(fod)3 reacted with electron-rich dipolarophiles such as vinyl ethers to give the trans-adducts with excellent diastereoselectivity <06T12227>. 

The results of a crystal structure formed by a trans opening of the BPDE l(+) to yield 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPTOH) shows a Cde (90) conformation of the ring. The 07-HOT and O8-H8 groups are de, and the 09-H9 and 010-H10 are also de. The torsion angles of the benzo ring are in best agreement with our second most stable structure, Cde, of the anti BDE-N2(G) trans adduct as is seen from Table III. In adduct formation to N2(G) the trans adduct is the major product (13-22) ... 

Also, Bose et al. [76] have shown that the steric course of /J-lactam formation can be influenced by the MW heating rate. For example, in the reaction of the benzoylox-yacetyl chloride 53 with the Schiff base 54 (Scheme 4.28) the cis adduct 55 is the main product at low irradiation power whereas high power favors the formation of the trans adduct 56. Lactams of this type can serve as intermediates for the side chain oftaxol and its analogs. 

The trans compound cannot be formed by a concerted reaction from the 33t-7t state because the predominant level perturbation is the almost degenerate interaction of K(jr) and 0(jr), that would give cis geometry of product. Since the trans adduct must be formed via biradical intermediate (the only other possibility), it has usually been convenient to suppose that the cis adduct is also formed from the same biradical intermediate. Another choice of mechanism is that cis compound is formed via a concerted reaction, and the trans compound arises from a biradical pathway. In this case, the spin prohibition could be outweighed by two factors, the favorable geometry and the stabilizing first-order perturbation. 

The reaction of 1 with hydrobromic acid gave quantitatively the cis adduct 14 (Scheme 11). The reaction of 1 with hydrochloric acid gave the cis adduct 15 in 79% yield and the trans adduct 16 in 18% yield. In these reactions, no other Si-Si bond cleavage products were obtained. The ladder polysilane 1 did not react with hydrofluoric acid. The reactions of 1,4-di-ter -butyl-2,2,3,3,5,5,6,6-octaisopropylbicyclo[2.2.0]hexasilane with hydrobromic acid and hydrochloric acid were attempted, but no reactions took place. This result is ascribed to steric hindrance by the tert-butyl groups on the bridgehead silicon atoms. 

Platinum on carbon did almost exactly the same thing but required a temperature of about 100°C to do so. With excess acetylene, only III formed. With tcrt-butylacetylene no II formed, probably because of steric hindrance, but I and III formed readily. 3-Hexyne reacted more slowly, required heat with chloroplatinic acid, and formed exclusively c/s-3-di-chlorosilyl-3-hexene. Trichlorosilane with platinum on carbon also added (57) to 1-alkynes or to phenylacetylene exclusively by cis addition to give only trans adducts. Later works (55) indicate that chloroplatinic acid and other soluble catalysts also give exclusively cis addition with a wide variety of Si—H compounds. 

Relatively polar diphosphine 8 has an elongated P-P bond, and thus exhibits unusual reactivity. The reaction of 8 with acrylonitrile or methyl acrylate proceeds at 50 °C in a chemo- and regioselective manner to afford the 1,2-addition product with the PPh2 group attached at the terminal position (Equation (64)).165 Tetrachlorodiphosphine reacts with cyclohexene to give trans-adduct presumably via an ionic pathway.166... 

Addition of CF3S02-XPh (X=S or Se) to alkenes occurs thermally to give trans-adducts via an ionic pathway (Equation (78)).212 The reaction of 2,3-dimethyl-l,3-butadiene gives a 1,4-adduct (80%, Z = 60 40). 

DesilylbrominationThis reaction was first used by Fleming et al. (8, 196 11, 75) in connection with protection of enones, but it is also useful for synthesis of chiral 5-alkylcyclohexenones. Thus reaction of (R)-(-)-l with lithium dialkyl-cuprates gives the trans-adduct 2 as the only product. Of several bromination reagents, only CuBr2 in DMF is useful for conversion of 2 to optically active 3. 

Dipolar species have been observed in the cycloaddition of polar intermediates. Thus cyclobutanes can be formed by non concerted processes involving zwitter ionic intermediates. The combination of an electron rich alkene (enamimes, enol ethers) and an alkene having electron withdrawing groups (nitro a cyano substituted alkenes) first gives a zwitter ion which can rotate about the newly formed bond before cyclization and gives both a cis and a trans adduct. 

How the relative orientation of substituents is preserved in the adduct is also illustrated by the combination of cyclopentadiene with the two isomers of 1, 2 disubstituted dienophile. Here the cis isomer gives the cis product and the trans isomer, the trans adduct. 

Methyl-4-phenylcyclohexa-2,5-dienone, a molecule containing a meso carbon, shows stereoselectivity in its reaction with p-tert-butylthiophenol catalyzed by cinchonidine (eq. [17]) (63). The trans cis ratio was found to be 3 1, with the cis adduct showing an e.e. of 77% and the trans adduct an e.e. of 50%. 

It is noteworthy that, at variance with bromination and chlorination which generally occur without isomerization of the disubstituted double bond, fluorine addition to the 1,2-bond of cis- and trans-1,3-pentadienes gives mainly the trans-adduct 13, besides smaller amounts of compounds 14-16 (equation 24). 

The same reaction scheme can also explain the stereochemical behavior of the addition of benzeneselenenyl chloride to 108 in methanol, which gives, in addition to the trans adduct 138, the analogous methoxy derivative 146, the cross-bonded chlorides 147 and 148, and the analogous epimeric methoxy adducts 149 and 150 (equation 130). 

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