Cyclizations diastereo selective

N-Acylnitroso compounds 4 are generated in situ by periodate oxidation of hydroxamic acids 3 and react with 1,3-dienes (e.g. butadiene) to give 1,2-oxazines 5 (Scheme 6.3). The periodate oxidation of 4-O-protected homo-chiral hydroxamic acid 6 occurs in water in heterogeneous phase at 0°C, and the N-acylnitroso compound 7 that is generated immediately cyclizes to cis and tranx-l,2-oxazinolactams (Scheme 6.4) [17a, b]. When the cycloaddition is carried out in CHCI3 solution, the reaction is poorly diastereo-selective. In water, a considerable enhancement in favor of the trans adduct is observed. 

Dirhodhun (II) carboxylate catalyzed cyclization of a series of y-alkoxy-a-diazoesters has been shown to proceed with substantial diastereoselectrvity, producing the 2,3,5-trisubstituted tetrahydrofiirans. Hie diastereo selectivity of the cyclization improved as the electron-withdrawing ability of the substituent R increased (Scheme 22, <96JOC6706>). 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

Ishihara, Yamamoto, and coworkers demonstrated that 26 SnCl4 is an artificial cyclase that is useful for not only achiral but also chiral substrates. The diastereo-selective cyclization of ( )-nerolidol (29) has been examined with 1 equiv of the achiral LBA, 2-methoxyphenol (32) SnCl4, in dichloromethane at —78°C (entry 1, Table 12.1). Cyclization of ( )-29 bearing an acid-sensitive allylic hydroxy group gives a complex reaction mixture, and the desired trans-fused 2-oxabicyclo[4.4.0]... 

Phosphorous oxychloride (POCI3) can also be used without further activation. For the synthesis of the antidepressant (/ )-(—)-rolipram 24, cyclization of the (3-hydroxy amide 21 with POCI3 gave the oxazoline intermediate 22. Diastereo-selective conjugate addition of cyanide gave the cyano derivative 23, which was further transformed to (/ )-( )-rolipram (Scheme 8.11). 

The synthesis of polysubstituted pyrrolidines has been achieved344 in a diastereo-selective and enantioselective manner via the zinca-ene-allene cyclization. In an extension of this work,345 the zinca-ene-allene reaction of polysubstituted enynes lithiated on the propargylic position has been used to prepare polysubstituted... 

Substituted 3-phenylsulfonyl-5-hydroxymethyl-THFs (e.g. 44) have been prepared chemo-, regio-, and diastereo-selectively via reaction of a y,5-cpoxycarbanion with aldehydes, RCHO.156 The initial aldol-type addition is non-diastereoselective, but reversible. The subsequent cyclization is selective, and exerts overall thermodynamic control. 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

In a parallel study, it was found that chelating chiral diamines 208 or 209 are well suited as ligands to promote Kumada-type couplings of primary and secondary alkyl halides 202 with aryl Grignard reagents 203 (entry 4) [281]. This reaction was applicable to alkyl bromides and alkyl iodides, while alkyl chlorides gave only low yields. Acetal and ester functions are tolerated. A notable feature is the stereoretentive arylation of fra s-a-bromo acetals with excellent diastereo-selectivity. The involvement of radicals is supported by the stereoconvergent formation of cxo-phenvI norbornane from both endo- or exo-bromonorbomane (cf. Part 1, Fig. 9) and radical 5-exo cyclizations (see below). 

Baldwin et al. employed 20 mol% 255 to synthesize isopropenyl-substituted prolinates 265 and kainic acid 268 in good yields from /V-prenylated haloamino acids 264 (Y=NC02R) (Fig. 65, entry 7) [318]. As observed before for many radical cyclizations employing trisubstituted alkenes as acceptors, the diastereo-selectivity remains, however, poor. 

Nevertheless, two other cases of diastereoselection in cyclizations of type b have been recorded. In the first case, protodesilylation of rac-2 and subsequent hemiacetal formation precedes conjugate addition to give rac-326. Whereas the hemiacetal formation proceeds diastereo-selectively, the conjugate addition step finally affords a 1 1 partition of epimeric products. 

Analogous cyclizations of citronellal can also be effected, albeit with lower diastereo-selectivity and in the racemic series with carbonyl M(II) complexes (M = Mo, W) [209],... 

C—H bond 280,281) comparison, only trace amounts of cyclopentane resulted from the CuSO -catalyzed decomposition of l-diazo-2-octanone or l-diazo-4,4-dimethyl-2-pentanone It is obvious that the use of Rh fOAc) considerably extends the scope of transition-metal catalyzed intramolecular C/H insertion, as it allows for the first time, efficient cyclization of ketocarbenoids derived from freely rotating, acyclic diazoketones. This cyclization reaction can also be highly diastereo-selective, as the exclusive formation of a /r< i5-2,3-disubstituted cyclopentane carboxylate from 307 shows The stereoselection has been rationalized by... 

Using tryptamine as the nucleophile, the Michael addition-cyclization strategy was extended to the enantioselective synthesis of the /J-carboline alkaloid system. Michael addition of tryptamine to the chiral acetylenic sulfoxides took place smoothly at room temperature. Either trifluoroacetic acid or p-toluene-sulfonic acid was effective as a catalyst for the cyclization step (Scheme 7). The results of the Michael addition-cyclization reaction sequence are summarized in Table 3. In general, we found that the indole moiety is more reactive than the dimethoxyaryl ring used in the tetrahydroisoquinoline synthesis. Therefore, the cyclization step could take place at a temperature as low as -60 °C. Also, p-tolu-enesulfonic acid resulted in a better diastereoselectivity. However, the diastereo-selectivity of the system is much less sensitive to the aryl substituents of the acetylenic sulfoxides compared to that of the tetrahydroisoquinoline system. Also, to our surprise, the steric factor on the chiral acetylenic sulfoxide has little effect on the diastereoselectivity. Even with the bulky 2-methoxy-naphthyl acetylenic sulfoxide lc [11], the diastereoselectivity still remained roughly the same as for 1 a and 1 b (Scheme 7) (Table 3). 

The imine (101) derived from a 2-aryltryptamine and ethyl glyoxylate undergoes a diastereo-selective spirocyclization to the indolenine (102) (Equation (27)). Replacement of the ethyl ester by chiral esters, such as the 8-phenylmenth-3-yl ester, leads to asymmetric induction at the spiro carbon atom <90HCA439>. Imines derived from tryptophan esters have also been studied as substrates for the Pictet-Spengler cyclization (e.g., <87tlii31 . Enantioselective cyclizations have made use of enantiomerically pure aldehydes and tryptophan esters <92H(34)517, 93JCS(pi)43i, 93T8589>. 

A -(a-Carboxyalkyl)tryptamines can be prepared by alkylation of a-amino acid ester by tryptophyl bromide. The chirality of the amino acid unit directs diastereo-selectivity in the range of 70-98% for cyclization with a variety of aromatic aldehydes. The best selectivity is obtained with relatively bulky amino acid substituents, as for valine and isoleucine. The reactions appear to occur under kinetic control and the stereoselectivity is consistent with the sterically preferred Felkin-Ahn transition state [336]. 

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