Cyclization, stereochemistry

Scheme 37 Favorable effect of an adjacent substituent on cyclization stereochemistry...

The analogous reactions of methyl ( , )-2,7,9-decatrienoate and methyl (Z, )-2,7,9-deca-trienoate again demonstrated the nondependence of cyclization stereochemistry on dienophile geometry8. 

A comparative study has been carried out of the effect on cyclization stereochemistry of the nature of the electron-withdrawing, dienophile-activating group15. 

Anticipates a late transition state such that double anomeric effect dictates cyclization stereochemistry... 

The early Escherunoser-Stork results indicated, that stereoselective cyclizations may be achieved, if monocyclic olefins with 1,5-polyene side chains are used as substrates in acid treatment. This assumption has now been justified by many syntheses of polycyclic systems. A typical example synthesis is given with the last reaction. The cyclization of a trideca-3,7-dien-11-ynyl cyclopentenol leads in 70% yield to a 17-acetyl A-norsteroid with correct stereochemistry at all ring junctions. Ozonolysis of ring A and aldol condensation gave dl-progesterone (M.B. Gravestock, 1978 see p. 279f.). 

Furthei-more, the cyclization of the iododiene 225 affords the si.x-membered product 228. In this case too, complete inversion of the alkene stereochemistry is observed. The (Z)-allylic alcohol 229 is not the product. Therefore, the cyclization cannot be explained by a simple endo mode cyclization to form 229. This cyclization is explained by a sequence of (i) e.vo-mode carbopallada-tion to form the intermediate 226, (ii) cydopropanation to form 227. and (iii) cyclopropylcarbinyl to homoallyl rearrangement to afford the (F3-allylic alcohol 228[166]. (For further examples of cydopropanation and endo versus e o cyclization. see Section 1.1.2.2.)... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

The course of the photochemically mediated isomerization of vinylazirines is dependent on the stereochemistry of the vinyl group, as is illustrated in Scheme 94a (75JA4682). Under thermal conditions the isomerization proceeds through formation of the butadienylnitrene and subsequent pyrrole formation. Analogous conversions of azirines to indoles have also been effected (Scheme 94b). It is possible that some of the vinyl azide cyclizations discussed in Section 3.03.2.1 proceed via the azirine indeed, such an intermediate has been observed... 

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

An example of preferred conrotatory cyclization of four-7c-electron pentadienyl cation systems can be found in the acid-catalyzed cyclization of the dienone 12, which proceeds through the 3-hydroxypentadienyl cation 13. The stereochemistry is that expected for a conrotatory process. 

There are also examples of electrocyclic processes involving anionic species. Since the pentadienyl anion is a six-7c-electron system, thermal cyclization to a cyclopentenyl anion should be disrotatory. Examples of this electrocyclic reaction are rare. NMR studies of pentadienyl anions indicate that they are stable and do not tend to cyclize. Cyclooctadienyllithium provides an example where cyclization of a pentadienyl anion fragment does occur, with the first-order rate constant being 8.7 x 10 min . The stereochemistry of the ring closure is consistent with the expected disrotatory nature of the reaction. 

The first objective was the conversion of L-tryptophan into a derivative that could be converted to pyrroloindoline 3, possessing a cis ring fusion and a syn relationship of the carboxyl and hydroxyl groups. This was achieved by the conversions shown in Scheme 1. A critical step was e. Of many variants tried, the use of the trityl group on the NH2 of tryptophan and the t-butyl group on the carboxyl resulted in stereospecific oxidative cyclization to afford 3 of the desired cis-syn stereochemistry in good yield. 

Wawzonek et al. first investigated the mechanism of the cyclization of A-haloamines and correctly proposed the free radical chain reaction pathway that was substantiated by experimental data. "" Subsequently, Corey and Hertler examined the stereochemistry, hydrogen isotope effect, initiation, catalysis, intermediates, and selectivity of hydrogen transfer. Their results pointed conclusively to a free radical chain mechanism involving intramolecular hydrogen transfer as one of the propagation steps. Accordingly, the... 

The iminium salt 165, derived from acid treatment of 1,4-dihydropyridine 164, on intramolecular cyclization on the indole nucleus gave pentacyclic compound 166 (83T3673). The tmns stereochemistry of H3 and H9 in 166 (biogenetic... 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

The fourth and final cyclization occurs by addition of the C13 cation to the 17,20 double bond, giving the protosteryl cation with 17jB stereochemistry. 

Figure 30.7 Photochemical cyclizations of conjugated dienes and trienes. The two processes occur with different stereochemistry because of their different orbital symmetries.

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

E,4Z,6Z,8 )-2,4,6,8-Decatetraene has been cyclized to give 7,8-dimethyl-1,3,5-cycloodati icne. Predict the manner of ring closure—comoiatory or disrotatory— for both thermal and photochemical reactions, and predict the stereochemistry of the product in each case. 

Vinyl radicals can also participate in 6-exo cyclizations. In pioneering work, Stork and his group at Columbia University showed that stereoisomeric vinyl bromides 20 and 21 (see Scheme 3) can be converted to cyclohexene 22.7 The significance of this finding is twofold first, the stereochemistry of the vinyl bromide is inconsequential since both stereoisomers converge upon the same product and second, the radical cyclization process tolerates electrophilic methoxycarbonyl groups. The observation that the stereochemistry of the vinyl bromide is inconsequential is not surprising because the barrier for inversion of most vinyl radicals is very low.8 This important feature of vinyl radical cyclization chemistry is also exemplified in the conversion of vinyl bromide 23 to tricycle 24, the key step in Stork s synthesis of norseychellanone (25) (see Scheme 4).9 As in... 

It is important to note here that both of the 5-exo radical cyclizations (133—>132—>131, Scheme 27) must proceed in a cis fashion the transition state leading to a strained mms-fused bicy-clo[3.3.0]octane does not permit efficient overlap between the singly occupied molecular orbital (SOMO) of the radical and the lowest unoccupied molecular orbital (LUMO) of the alkene. The relative orientation of the two side chains in the monocyclic radical precursor 134 is thus very significant because it dictates the relationship between the two outer rings (i. e. syn or anti) in the tricyclic product. The cis-anti-cis ring fusion stereochemistry of hirsutene would arise naturally from a cyclization precursor with trans-disposed side chain appendages (see 134). 

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