Stereoselectivity in Cyclization

The diastereoselectivity in 5-exo cyclization of a range of chiral acyl radical equivalents derived from 1,3-dioxolanes and dioxanes has been investigated. Results indicate that selectivity was poor for radicals which cyclised via a twist-boat conformation but high when l,3-dioan-2-yl radicals containing an imposed chair-like conformation were used. The 5-exo cyclizations of a-phenylsulfenyl radicals, 

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Table 10 Stereoselectivity in Cyclizations to 2,3,5-Trisubstituted Tetrahydropyrans (Equation 42)...

The stereoselectivity in cyclizations of vinyl ether systems to form furanosyl disaccharides is controlled by both the side chain substituent (1,4-asymmetric induction) and the configuration of the existing pyranoside linkage (equation 49).142 Substrates with no side chain substituent show no stereoselectivity. 

Few examples of stereoselectivity in 6-exo cyclizations to piperidine derivatives have been reported. The aminocarbonylation reactions of systems with an allylic hydroxy substituent that are quite stereoselective in cyclization to pyrrolidine systems (equation 106) are nonselective in cyclizations to piperidine systems.237 Cyclizations with mercury(II) acetate also proceed with low selectivity (59-69% cis isomer).237 A series of aminoalditols have been synthesized by aminomercuration of oxygen-substituted 6-(/V-benzylamino)hexenes. The stereochemistry of these cyclizations (equation 112)247 does not appear... 

Two approaches to convergent steroid syntheses are based on the thermal opening of benzocyclobutenes to the o-quinodimethane derivatives (see p. 80 W. Oppolzer, 1978 A) and their stereoselective intramolecular Diels-Alder cyclizations. T, Kametani (1977 B, 1978) obtained (+ )-estradiol in a six-step synthesis. The final Diels-Alder reaction occurred regio- and stereoselectively in almost quantitative yield, presumably because the exo transition state given below is highly favored over the endo state in which rings A and D would stcrically inter-... 

Stereoselectivity in the condensation reaction of 2-arylethylamines with carbonyl compounds to give 1,2,3,4-tetrahydroisoquinoline derivatives was somewhat dependent on whether acid catalysis or superacid catalysis was invoked. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed with trifluorosulfonic acid (TFSA) as compared with the weaker acid, trifluoroacetic acid (TFA). Compound 43 was cyclized in the presence of TFA to give modest to good transicis product ratios. The analogous compound 44 was cyclized in the presence of TFSA to give slightly improved transicis product ratios. 

The intramolecular cyclization of enolate of l-tryptophyl-3-((3-ketobutyl) pyridinium bromide (160) afforded enamine 161, which undergoes stereoselective acid cyclization with cone. HCl to give the pentacyclic ketone 162 (Catalytic hydrogenation of 162 led to (d,l)-pseudoyohimbone (163) (76JA3645). Again, H3-H15 were found to have the tmns configuration in 162. 

The asymmetric synthesis of (4i ,9S, 9ai )-4-phenyl-l-trimethylsilyloxy-9-vinylperhydropyrido[2,l-c][l,4]oxazine by a high level of stereoselectivity in the cyclization of (3i ,5i )-5-phenyl-3-phenylsulfanyl-4-(6-trimethylsila-nylhex-4-enyl)-2-trimethylsilyloxymorpholine was rationalized via AMI calculations (98T10309). 

The smooth cyclizations of ( )- and (Z)-/V-( 3-alkenyl/ethoxy lac tarns with formation of a six-membered ring (via a chair-like transition state) occur completely stereoselectively in quantitative yield with retention of the geometry of the double bond913. 

An example of a surprisingly facile and stereoselective formation of an eight-membered lactone from an acyclic precursor diene ester was observed during the total synthesis of the antitumor agent octalactin A (148) (Scheme 27) [81]. The dense substitution pattern in cyclization substrate 146 presumably imposes... 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

Radical cascades that feature a 7-exo acyl radical cyclization followed by a 6-exo or 5-exo alkyl radical cyclization proceed with very good yields and diastereoselectivities. Two examples are shown in Reaction (80), where treatment of 100 with E3B, air, and (TMS)3SiH provided the tricycle 101 in excellent yields as a single diastereomer. Interestingly, the bulky silyl ether moiety is not required to achieve stereoselectivity in this process. 

The cis configuration of 96 was elucidated by X-ray structure analysis. The data suggest that the cyclization reaction of the anion 95 generated from 94 to 91a proceeds stereoselectively in the solid state [16]. 

A deuterium-labeling study of a reaction of this type demonstrated syn stereoselectivity in both the oxypalladation and P-elimination, which indicates that the cyclization occurs by internal migration, rather than by an anti nucleophilic capture.113 This particular system also gives products from double-bond migration that occurs by reversible Pd(II)-D addition-elimination. 

An interesting stereochemical profile of this cyclization is that in the five-membered product structures, substituents PhS and OH groups are placed cis to each other, whereas in six-membered products the placement is trans (Table 6, entry 7). The cis selectivity in the five-membered ring systems is not affected by a and fi-substituents of the alkoxides (entries 2, 3 and 4), indicating that the steric effect is not the dominant factor. Instead, interaction between the oxido and carbene center composes a five- (or seven-) membered transition state 28, which allows the carbene to abstract the nearest quasi axial hydrogen as a hydride to produce a carbonyl intermediate 29, leading to the cyclization products 27 and 30 (Scheme 13, Eq. 1). Similarly, the stereoselective stepwise cyclization of cis- and rra s-2-(3,3-dithiopropyl)cyclohexanol to 2-phenylthio-... 

The very first example of the catalytic reductive cyclization of an acetylenic aldehyde involves the use of a late transition metal catalyst. Exposure of alkynal 78a to a catalytic amount of Rh2Co2(CO)12 in the presence of Et3SiH induces highly stereoselective hydrosilylation-cyclization to provide the allylic alcohol 78b.1 8 This rhodium-based catalytic system is applicable to the cyclization of terminal alkynes to form five-membered rings, thus complementing the scope of the titanocene-catalyzed reaction (Scheme 54). 

Lithium ( )- or (Z)-5-alkenylamides are converted regio- and stereoselectively in a 5-exo-fng-cyclization of an intermediate amide radical to substituted pyrrolidines [84]. 

With diphenylmethylborneol as the chiral auxiliary high face selectivities have been achieved and the all-trans-2-a k-oxycarbonyl-3,4-diphenylcyclopentanone has been converted to dimethyl (3/f, 4/ )-3,4-diaryladipate with 87 to 95% ee [267, 268]. With an isopropyloxazolidinone as the chiral auxiliary the stereoselectivity in the all-trans cyclized hydrodimer was strongly affected by the electrolyte employed [269, 270]. 

In Yamada s retrosynthetic analysis (Scheme 11), elisabethin C (26) is traced back to lactone 64 which would be converted into 26 by deoxygenation and chain elongations. Key intermediate 64 could be obtained by a stereoselective Dieckmann cyclization. The required ester lactone precursor 65 would be accessible from 66 by a series of oxidation reactions. Further disconnection would lead to commercially available (+)-carvone (67). Stereoselective successive alkylation of 67 and reduction of the enone should deliver 66 [30]. 

Table 5. Influence of supporting electrolyte on stereoselectivity in the reductive cyclization of 52 and 53...

Amputch MA, Little RD (1991) Tetrahedron 47 383. Utley JHP, (1987) Electrogenerated bases. In Steckhan E (ed) Topics in current chemistry. Springer, Berlin Heidelberg New York, p 133 Little RD, Sowell CG (1991) Stereoselection in electroreductive cyclization. Construction of a Corey lactone precurser. In Little RD, Weinberg NL (eds) Electroorganic synthesis, festschrift for Manuel M. Baizer. Dekker, New York, p 323 Shono T, Mitani M (1971) J. Am. Chem. Soc. 93 5284... 

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