Diastereoselectivity intramolecular reactions

Finally, by a diastereoselective intramolecular double Michael reaction of a lithium dieno-late to an a,j6-unsaturated ester moiety, a spiro-fused bicyclo[2.2.2]octane may be prepared. These MIMIRC form the key step in the synthesis of ( )-atisine361 and (-t-)-alisirene362-365. 

Photolysis of chromium alkoxycarbene complexes with aldehydes in the presence of Lewis acids produced /J-lactones [83]. Intermolecular reactions were slow, low-yielding, and nonstereoselective, while intramolecular reactions were more efficient (Eqs. 19 and 20). Subsequent studies showed that amines, particularly DMAP, could also catalyze this process (Table 13) [84], resulting in reasonable yields and diastereoselectivity in intermolecular cases. 

Diastereoselective intramolecular cycloaddition of nitrones is useful for constructing nitrogen- containing cyclic structures. The reaction serves as a key step in a number of natural product syntheses.63 Tufarriello and coworkers have used this strategy for preparing cocaine and other alkaloids.74 As a classical example, enantioselective total synthesis of (+)-luciduline is presented in Scheme 8.13, in which a useful feature of the 1,3-dipolar addition of nitrones is nicely illustrated.75... 

A diastereoselective intramolecular hetero-Diels-Alder reaction of optically active 428 gave unstable 1,3,4,8,9,9a-hexahydropyrido[2,l-f][l,3]oxazin-l-one 429 (X = 0), and l,3,4,8,9,9a-hexahydropyrido[l,2-(z]pyrazin-l-one 429 (X = NTs) (Equation 80) <2003JA4970, 2004T10277>. In the case of pyrido[l,2- ]pyrazine, the reaction was carried out in the presence of 2,6-di- /-butyl-4-methylphenol. 

A diastereoselective intramolecular thermal carbonyl-ene reaction of a single enantiomer of keto ester 7 afforded the C5-C14 fragment of the jatrophane skeleton (Scheme 3).11 The key reaction was performed under thermal conditions (180 °C, 3 days) to afford only the m-compounds 8 and 9 in a 5 1 diastereomeric ratio. The kinetic preference for the m-isomers was explained by the less strained m-annulated transition states. 

In a similar fashion, allylboronates can be used as allylation reagents under hydroformylation conditions. Thus condensed 1,5-oxazadecalin systems are achieved via tandem hydroformylation/allylboration/hydroformylation sequences starting from an N-allyl-y-amidoallylboronate (Scheme 23) [77,78]. The aldehyde obtained from a regioselective hydroformylation undergoes diastereoselective intramolecular allylboration to give an intermediate al-lylic alcohol derivative. The reaction does not stop at this stage, since this... 

Table 9 Highly diastereoselective intramolecular Stetter reaction...

Based on the precedent of Van Leeuwen and Roobeek, livinghouse and co-workers screened a variety of electron-deficient phosphine/phosphite ligands for the rhodium-catalyzed [4-1-2] reaction, which provided an alternative catalyst system for the formation of 5,6- and 6,6-ring systems [13]. The most notable of these was the tris-(hexafluoro-2-propyl) phosphite-modified rhodium complex, which was applicable to both carbon- and oxygen-tethered substrates, and also provided the first example of a facial-directed diastereoselective intramolecular rhodium-catalyzed [4-i-2] reaction (Eq. 4). 

Intramolecular addition of hydroxylamines and hydroxamic acids to the non-activated double bonds is possible through oxidative cyclization. Reaction of O-Acyl fi,y-unsaturated hydroxamates (e.g. 56, equation 38) with bromine provides 3,4-substituted iV-hydroxy -lactams such as 57 with high diastereoselectivity. Analogous reaction of O-benzyl hydroxylamine 58 (equation 39) with iodine results in five-membered cyclization with 2 1 ratio of diastereomers. ... 

The convergence of the nitronate and nitrile oxide cycloadditions has allowed for the direct comparisons of yields and stereoselectivities of the two processes. For intramolecular reactions, the nitronate dipole typically required longer reaction times and/or elevated temperatures (22,98,135), however, the nitronate cycloaddition shows considerably higher diastereoselectivity (Table 2.42). Interestingly, the diastereoselectivity is dependent on the placement of a substituent on the tether. In the case of the silyl nitronate derived from 172, the diastereoselectivity is controlled by the substituent at C(l), while cyclization of the analogous nitrile oxide is governed by the substituent at C(l ) (Scheme 2.10) (124). 

For intramolecular 1,3-dipolar cycloadditions, the application of nitrones and nitrile oxides is by far most common. However, in increasing frequency, cases intramolecular reactions of azomethine ylides (76,77,242-246) and azides (247-259) are being reported. The previously described intermolecular approach developed by Harwood and co-workers (76,77) has been extended to also include intramolecular reactions. The reaction of the chiral template 147 with the alkenyl aldehyde 148 led to the formation of the azomethine ylide 149, which underwent an intramolecular 1,3-dipolar cycloaddition to furnish 150 (Scheme 12.49). The reaction was found to proceed with high diastereoselectivity, as only one diaster-eomer of 150 was formed. By a reduction of 150, the proline derivative 151 was obtained. 

A special case of diastereoselective alkylation reaction via azaenolates is the intramolecular cyclization of metalated 4,5-dihydro-2-(5-iodohexyl)-4,4-dimethyloxazole which furnishes the thermodynamically less favored cri-2-methylcyclopentanecarboxylic acid derivative 8 preferentially32. 

Inter- and intramolecular reactions between a propargyiic carbocation equivalent stabilized by Co2(CO)6-coordination and enol derivatives also provide a good method for the carbon-carbon bond formation at the propargyiic carbon of propargyiic alcohols and their derivatives. Many diastereoselective and enantioselective propargyiic alkylation reactions at the propargyiic position take place between chiral propargyiic cation equivalents and enol derivatives. 

Based on this precedent, Nelson et al. used an intramolecular reaction in the total synthesis of (-)-rhazinilam. In this context, trisubstituted allenes are excellent precursors for a diastereoselective heterocyclic annulation that highlights the usefulness of this reaction in target-oriented synthesis [49]. In this case, the aforementioned catalyst that yielded the best results was [AuPPh3OTf], affording a higher yield and diastereoselectivity than Pd(II). 

Diastereoselective ene reactions. Thermal cyclization via an intramolecular ene-tvpc reaction of the (7.)-1,6-diene 1 results in a mixture of trans-1 and cis-2 in the ratio 75 25. This reaction is markedly accelerated by addition of (C2H5)2AIC1, with only trans-1 being formed. The (E)-isomer of I is also cyclized thermally to give... 

Superacid-catalysed intramolecular reactions of some dicationic electrophiles have been investigated.36 The positively charged centres migrate apart and this chemistry gives a new synthetic route to aza-polycyclic compounds. The polycyclic compound (26) can, for example, be formed from reaction of 2-phenyl-3-(l-hydroxy-2-phenyl-ethyl)quinoline (25) with CF3SO3H at 25 °C, loss of water and benzene being involved. Highly diastereoselective polycyclization of homo(polyprenyl)arenes [e.g. (27)... 

To the best of our knowledge only one example of diastereoselective intramolecular Ugi reaction employing a ketoacid is known [80]. The condensation of acid 89 with (S)-l-phenylethylamine proved to be stereoselective, giving a mixture of the four possible diastereoisomers 90 in a 42 42 8 8 ratio, with the trans stereoisomers pre-... 

Cyclic amino-carbenes, in molybdenum carbonyls, 5, 457 Cyclic bis(phosphine) dichlorides, with iron carbonyls, 6, 48 Cyclic carbenes, as gold atom ligands, 2, 289 Cyclic carbometallation, zirconium complexes, 10, 276 Cyclic carbozirconation characteristics, 10, 276 intermolecular reactions, 10, 278 intramolecular reactions, 10, 278 Cyclic dinuclear ylides, and gold , 2, 276 Cyclic 1,2-diols, intramolecular coupling to, 11, 51 Cyclic enones, diastereoselective cuprate additions, 9, 515 Cyclic esters, ring-opening polymerization, via lanthanide catalysis, 4, 145 Cyclic ethers... 

As an obvious extension of the benzoin reaction, the cross-coupling of aldehydes or of aldehydes and ketones was first achieved with the thiamine-dependent enzyme benzoylformate decarboxylase. This linked a variety of mostly aromatic aldehydes to acetaldehyde to form the corresponding a-hydroxy ketones, both chemo- and stereoselectively [31]. Synthetic thiazolium salts, developed by Stetter and co-workers and similar to thiamine itself [32], have been successfully used by Suzuki et al. for a diastereoselective intramolecular crossed aldehyde-ketone benzoin reaction during the course of an elegant natural product synthesis [33], Stereocontrol was exerted by pre-existing stereocenters in the specific substrates, the catalysts being achiral. 

A unique member of the seven carbon carbaketose family, namely hept-2-uloseptanosylamine 342, was assembled by Mandal [78,79] during a remarkable total synthesis of chiral carbocyclic nucleosides from D-glucose. Here, a diastereoselective intramolecular nitrone cycloaddition reaction was the decisive move to install the carbaseptanose ring system (Scheme 56). 

The highly diastereoselective intramolecular aza-Cope-Mannich reaction was used in the total synthesis of (i)-pancracine (11), an alkaloid natural product5... 

Reaction of lithiated allyl sulfone 60 with cyclopentenone gave the y-1,4-addition product (61). On treatment with LiOH the enolate intermediate 62 underwent a completely diastereoselective intramolecular conjugate addition onto the vinyl... 

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