Five contiguous stereocenters

In the event, treatment of a rapidly stirred solution of 3 and sodium acetate in MeOH-tbO at 38 °C with PdCl2 results in the fomation of carpanone (1) in 46% yield. The ordered unimolecular transition state for the oxidative coupling reaction furnishes putative bis(quinodimethide) 2 stereoselectively. Once formed, 2 readily participates in an intramolecular Diels-Alder reaction4 to give carpanone (1). Two new rings and all five contiguous stereocenters are created in this spectacular sequential transformation.5... 

The construction of the five contiguous stereocenters required for a synthesis of compound 3 is now complete you will note that all of the substituents in compound 5 are positioned correctly with respect to the carbon backbone. From intermediate 5, the completion of the synthesis of the left-wing sector 3 requires only a few functional group manipulations. Selective protection of the primary hydroxyl group in 5 as the corresponding methoxymethyl (MOM) ether, followed by benzylation of the remaining secondary hydroxyl, provides intermediate 30 in 68 % overall yield. It was anticipated all along that the furan nucleus could serve as a stable substi-... 

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

A different [3+2] cycloaddition occurs on reaction of certain vinyldiazoacetates with styryl ethers [30], Although the mechanistic details are not known, the reaction is considered to be a concerted process and furthermore, it displays very high levels of stereocontrol. As illustrated in the Rh2(S-DOSP)4-catalyzed reaction shown in Eq. (22), the [3+2] cycloadduct 42 is formed as the all-czs di-astereomer in 98% ee. Cuprate addition to 42 stereoselectively generates the cyclopentane 43 with five contiguous stereocenters. 

Control of acyclic stereochemistry. The five contiguous stereocenters of aldehyde 5, an intermediate in Kishi s total synthesis of monensin (6), were established by the hydroboration reactions of 1 and 3, which afforded 2 and 4, respectively, with high stereoselectivity (8 1 diastereomer ratio for 1 12 1 for 3). Kishi argues that the... 

The first total synthesis of barbacenic acid, a bisnorditerpene containing five contiguous stereocenters, was achieved by A. Kanazawa et. al. They started out from a Wieland-Miescher ketone analogue that could be synthesized with high yield and excellent enantioselectivity by the procedure of S. Takahashi. According to this procedure, the Michael addition product 2-methyl-2-(3-oxo-pentyl)-cyclohexane-1,3-dione was cyclized in the presence of (S)-(-)-phenylalanine and D-camphorsulfonic acid. 

LiOAc ) and/or reaction conditions are involved. 1,3-Dinitropropane and especially 2-substituted homologues, react with enals to provide 2,4-dinitrDcyclohexanols with up to five contiguous stereocenters and ee up to 94%. ... 

What s more, the addition of nilroalkanes to ot,P-unsaturated aldehydes followed by an intramolecular Henry reaction which led to the formation of highly substituted cyclo-hexanols with control over five contiguous stereocenters was illustrated (Scheme 1.79) [124], This novel domino reaction catalyzed by diarylprolinol sily 1 ether 128 proceeded in moderate to good yields with high diastereo- and enantioselectivity. 

A particularly impressive example of the Prins-pinacol chemistry is illustrated in Scheme 57 where tetrahydrofuran 214 having five contiguous stereocenters was generated in 89 % yield from the treatment of acetal 213 with SnCLj. As illustrated, 214 served as a precursor to the natural product (-)-citreoviral [65]. 

Treatment of 25 under reductive dehalogenation conditions in the presence of excess furan 3 afforded cycloadduct as an inseparable mixture of diastereomers (8 1 1), with the major (endo) diastereoisomer as the desired product. After DIBAL reduction of the ketone, the desired alcohol 31 was isolated as a single isomer in 50% yield for the two steps after chromatographic purification (Scheme 19.14). In two simple transformations, four of the five contiguous stereocenters of the natural product fragment were set, three of which arose from cycloaddition ... 

In the initial applications of Diels-Alder chemistry to yohimbine alkaloid synthesis, the Kametani (24-27) and Takano (28) groups have both examined reactions between furan derivatives and maleic anhydride. In the initial investigations of Kametani and his coworkers (24) (Scheme 3.10), the Diels-Alder adduct (57) of furan and maleic anhydride underwent bromolactonization to give the tricyclic carboxylic acid 58 (94). This compound has four [C(15), C(16), C(17), and C(18)] of the five contiguous stereocenters of the reserpine E-ring in place. Acid 58 was converted to diazoketone 59 which underwent Wolff rearrangement followed by tryptamine trapping to afford amide 60. Bischler-Napieralski cyclization of this substance afforded the tetracyclic... 

During the course of their studies on the chromium-mediated [6 + 2]- and [6 + 2 + 2]-reactions, the Rigby group uncovered a new four-component [6 + 2 + 2 + 2]-cycloaddition.167 When the two terminal alkynes are connected by three methylene units, an anticipated [6 + 2 + 2]-cycloaddition occurs in a moderate yield. Surprisingly, when the alkynes are tethered by four or five methylenes, a third alkyne is incorporated in an overall [6 + 2 + 2 + 2]-process (Scheme 71). The authors propose that the [6 + 2 + 2 + 2]-cycloaddition products arise from a [3 + 2] reaction of an alkyne with the initially formed [6 + 2 + 2]-reaction products (Scheme 72). These reactions greatly increase structural complexity by stereoselec-tively converting four achiral components to a pentacyclic product with six contiguous stereocenters. 

The methodology was extended to the desymmetrization of triones 151 (Scheme 8.41) [119], and diastereo- and enantioselective conjugate arylation/aldol cycliza-tion led to the formation of five- and srx-membered diquinane and hydroquinane structures 152 containing four contiguous stereocenters. 

PGF2a- The cyclopentane ring of the Corey lactone (9) is the host of four contiguous stereogenic centers. Retrosynthetic simplification of 9 provides 10, a construct which is more complex than 9 Nevertheless, intermediate 10 possesses structural features that satisfy the requirement for the iodolactonization transform. The iodolactone in 10 constitutes the retron for the iodolactonization transform.11 Cleavage of the indicated bonds in 10 sacrifices two of the five stereocenters and provides unsaturated carboxylic acid... 

Compound 1 was the first cyclopentane-based NK-1 receptor antagonist development candidate at Merck. It contains five stereocenters a central core possessing three contiguous all-trans stereocenters, a pendent bis(trifluoromethyl)-benzyHc ether, and a nipecotic acid moiety (Figure 7.1). Key to the successful preparation of 1 was construction of the trans, trans-cyclopentyl core and installation of the unsymmetrical secondary-secondary (sec-sec) ether. The preparation of 1 is the focus of this chapter. 

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