Oppolzer cyclization

An Oppolzer cyclization was used in the stereoselective synthesis of (-)-eryth-rodiene (95), a sesquiterpenoid isolated from Caribbean coral (Scheme 12.30).192... 

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-... 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Oppolzer and coworkers further demonstrated that an alternative mode of cyclization led to the total synthesis of khusimone (Scheme 51) . 

Intramolecular metallo-ene reactions are thermodynamically favored and are thus more efficient than the intermolecular versions. The classical distinction of the cyclization modes, suggested by Oppolzer, depends on the carbon of the allylic organometallic (ene-component) to which the alkene or the alkyne (enophile) is linked (equation 77)5,6. 

Camphorsulfonyl)imine has been reported as a by-product of reactions involving the camphorsulfonamide.2 5 Reychler in 1898 isolated two isomeric camphorsulfonamides,2 one of which was shown to be the (camphorsulfonyl)imine by Armstrong and Lowry in 1902.3 Vandewalle, Van der Eycken, Oppolzer and Vullioud described the preparation of (camphorsulfonyl)imine in 74% overall yield from 0.42 mol of the camphorsulfonyl chloride.6 The advantage of the procedure described here is that, by using ammonium hydroxide, the camphorsulfonyl chloride is converted to the sulfonamide in >95% yield.7 The sulfonamide is of sufficient purity that it can be used directly in the cyclization step, which, under acidic conditions is quantitative in less than 4 hr. These modifications result in production of the (camphorsulfonyl)imine in 86% overall yield from the sulfonyl chloride. 

Products from such reactions have been employed in the synthesis of terpenes via intramolecular Diels-Alder cyclizations (94-96). If the bulk of the carbonyl reagent is increased by inclusion of a large adjacent protecting group, much improved regioselectivity toward terminal attack is acheived (97,98). A complementary approach has been adopted by Oppolzer who... 

The intramolecular oxime-alkene cyclizations, also known as tandem 1,2-prototropic-cycloadditions, with nonactivated alkenes was first reported by Oppolzer and Keller in 1970 <70TLiii7> but their use for the heterocycles of this chapter was first reported in the 1990s <91T4007>. The methodology is shown in Schemes 46 and 47 in an expedient synthesis of chiral, unfunctionalized... 

An asymmetric permanganate-promoted oxidative cyclization of 1,5-dienes using a chiral phase-transfer catalyst was recorded <2001AGE4496>, and a diastereoselective permanganate-mediated oxidative cyclization with an Oppolzer sultam has been employed in the total synthesis of m-solamin <20020L3715>. In a metal-oxo-mediated approach to the synthesis of 21,22-di- /)7-membrarollin based on the use of a camphor-derived Oppolzer sultam as... 

A separate study of the alkylations of 1 has been reported by Oppolzer and co-workers. The group has employed LDA, LiTMP, and n-C4Hs,Li to metalate 1. The resulting anion condenses with a variety of electrophiles (primary alkyl bromides, iodides, tosylates, disulfides, and acyl derivatives) to afford the corresponding monosubstituted derivatives in 30-95% yield. If the alkyl group contains a double bond in the 4- or 5-position, polycyclic compounds are prepared by thermal extrusion of SO2 followed by intramolecular Diels-Alder cyclization. 

The iwesence of an amide linkage on the connecting chain exerts a significant influence first observed by Oppolzer, - are related to conformadonal preferences exerted by the amide unit. Thus urethane (65) presumably cyclizes exclusively through transition state (71c ) since (Ihrans) is destabilized by an eclipsing interaction between H(8) and... 

Cyclization of 1,6-dienes containing Oppolzer s auxiliary is promoted by permanganate affording fM-2,6-bis-hydroxyalky 1-te tra hydropyrans <2004TL7269>. 

In an imaginative construction of the angular triquinane ( )-hirsutene (158), Oppolzer and Robyr reported the carbonylative closure of allylic carbonate 155 to yield bicyclooctanes 156 and 157 (Scheme 6-27) [57]. In this multistep transformation, a alJylpalladium intermediate arising from the allylic carbonate 155 undergoes intramolecular Heck insertion of the pendant alkyne. Carbonylation of the resulting vinylpalladium intermediate, another Heck cyclization, and a second carbonylation then provide a mixture of acids, which after esterification yield esters 156 and 157 in good yield. 

Oppolzer, W., Robyr, C. Synthesis of ( )-hirsutene by a catalytic allylpalladium-alkyne cyclization/carbonylation cascade. Tetrahedron 1994, 50, 415 24. 

Felkin product (69% ds, 2-anti). A (Z)-titanium enolate usually favours the anti-Felkin adduct, and the subsequent Oppolzer synthesis of denticulatins A (see Scheme 9-69) highlights this behaviour (see also Scheme 9-30) however, exceptions can be found (Scheme 9-45). Oxidation of the C3 and Cn hydroxyls of 258, and cyclization, under carefully controlled conditions to preserve the configuration of the Cio stereocenter, then allowed the selective synthesis of denticulatin B. 

An ingenious extension of the Tsuji-Trost reaction was the cornerstone of Oppolzer s enantioselective synthesis of a heteroyohimbine alkaloid, (-t-j-B-isorauniticine (267) [117]. Substrate 263 was prepared from a commercially available glycinate equivalent by Malkylation, installation of the sultam chiral auxiliary followed by a sultam-directed C-alkylation. As illustrated in Scheme 48, the crucial double cyclization was accomplished by the treatment of 263 with Pd(dba), Bu,P, in the presence of carbon monoxide (1 atm) in acetic acid to give enone 264 and two other stereoisomers in a 67 22 11 ratio. In this case, an allyl carbonate, rather than an allyl acetate, was used as the allyl precursor. Since carbonate is an irreversible leaving group, formation of the n-allylpalladium complex occurs readily. In the presence of Pd(0), the allylic carbonate is converted into a n-allylpalladium complex with concurrent release of CO, and... 

Another (- )-P-necrodol synthesis has been described by Oppolzer and Schneider. Unfortunately this became known too late for a scheme to be included here, but it depends on a stereoselective addition of methylcopper to a camphor-derived sultamide 350, occurring from the P-/ e-bottom face. A further key step was the cyclization of the chloride 351 with activated magnesium and... 

Two important works were reported by others in the 1990s. First, Oppolzer in Switzerland found that the intramolecular cyclization as shown in D 114 of Figure 4.71 could best be accomplished with titanium tetrachloride in the presence of ethyldiisopropylamine in dichloromethane at —78 °C.125 Then, Matteson in the USA synthesized pure and crystalline (25,35,17 )-114 by employing his organoborane chemistry.126 This prompted us to attempt our second synthesis of (25,35,1 5)-114 to obtain it as crystals. 

Chiral auxiliaries are capable of controlling the absolute steric course of radical reactions. 8-Phenylmenthyl ester or an amide derived from Oppolzer s camphor sultam can be utilized for enantioselective ring closure to cyclopentane, the chiral auxiliary directing the addition to the alkene. The reductive radical cyclization of 8-phenylmenthyl 2-phenylthio-6-heplenoale at 80 °C gives four isomeric cyclopentane derivatives in an overall yield of 90 % 3. The reaction proceeds with modest cis irons ratio, but a considerably higher RiS selectivity of 80 20. 

It appears that a o-quinodimethane is also an intermediate in this transformation, and the cycloaddition must have occurred through an exo transition state which leads to the product stereochemistry observed. A similar stereochemical situation probably applies in Oppolzer s case [Eq. (23)], but the trans isomer apparently partially epimerized thermally to the cis isomer under the cyclization conditions. 

Interestingly, the putative o-quinodimethane intermediate in this case undergoes cyclization with regiochemistry opposite to Oppolzer s system. Whether this result is due to the nature of the bridge between diene and dienophile or to some sort of polar interaction is not clear. From the product stereochemistry it is evident that cyclizations must have occurred via an endo-phenyl transition state. 

These cyclizations occur via C—N bond formation and have been used for the synthesis of a number of saturated <5-sultams and / -sultams. In particular Helferich, Doss, Zeid and coworkers have reported the synthesis of several, mainly N-aryl, saturated <5-sultams via cyclization of chloroalkanesulphonamides as outlined in equations 185-187236,244,245. Oppolzer and coworkers have synthesized y-sultams as part of their work on chiral... 

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