Diastereoselective cycloisomerization

Organolithium mediated cycloisomerization of chiral aminoalkenes may proceed with high diastereoselectivities when favored by the substrate geometry. The last step ofthe enantioselective synthesis of ( ) codeine (80), reported by Trost and Tang [121], consisted of an intramolecular hydroamination. Treatment of amine 79 with LDA or wBuLi in refluxing THF left the starting material unreacted. However, irradiation of the amine/LDA solution with a 150 W tungsten lamp led to diastereoselective cycloisomerization to form ( ) codeine (80) (Eq. 11.11). 

Diastereoselectivity was observed as the result of stereoinduction (Equation (41)), giving preferential formation of the 1,2-trans products. Enhancement of the diastereoselectivity in the cycloisomerization of enyne 65a n= 1) was observed with the use of the catalyst bearing the sterically demanding Cp ligand 64. 

Incorporation of the carboxylic acid group into the substrate also had an effect on the stereochemistry of the Alder-ene products. Trost and Gelling60 observed diastereoselectivity in the palladium-catalyzed cycloisomerization of 1,7-enynes when the reactions were conducted in the presence of A,A-bis(benzylidene)ethylene diamine (BBEDA, Figure 2). They were able to synthesize substituted cyclohexanes possessing vicinal (Equation (53)) and... 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

In the cycloisomerization reaction of 271, high diastereoselectivity was also observed, depending on the nature of the R group connected to the nitrogen atom [138],... 

In 1988, Trost and Tour published the cycloisomerization of an ene-allene using a nickel-chromium catalyst [134]. For example, 211 diastereoselectively led to 212 (Scheme 15.68). In the total synthesis of ( )-petiodial, this nickel-chromium system failed, but a palladium catalyst was successful [135]. 

Parker has outlined an elegant, enantioselective synthesis of L-vancosamine derivatives commencing from noncarbohydrate precursors (Scheme 17.38) [116]. This approach features a diastereoselective allenylstannane addition and W(CO)5-catalyzed cycloisomerization to construct the pyranose core. Oxidative cyclization of the C4-carba-mate 128 is performed with 10 mol% Rh2(OAc)4 and proceeds stereospecifically to give the crystalline oxazolidinone 129 (86%). All told, synthesis of this useful L-vancosa-mine glycal equivalent covers seven steps from (S)-(-)-ethyl lactate 127 and is accomplished in 44% overall yield. 

On the other hand, Takacs and coworkers added organometallic reducing agents to the reaction mixture and promoted the formation of low-valent iron(O) bipyridine complexes. The mechanism of the low-valent iron-catalyzed Alder-ene reaction involves coordination of the two starting materials within the ligand sphere of the iron, which makes the Woodward-Hoffmann rules for such reactions obsolete [11]. Thereby, the scope of the reactions was broadened so that alkenes and 1,3-dienes could also be used as educts in a formal [4 + 4]-cycloisomerization (Scheme 9.3) [12]. Intriguingly, the diastereoselectivity of the cydopentane products can be influenced by either the application of the 2Z-isomer 3 or the 2 E-isomer 4. Especially the E-isomers 4 gave almost exclusive cis selectivity [13]. 

In previous work using Pd catalysts, cycloisomerizations involving substrates bearing siloxy groups at the allylic position generated 1,3-dienes preferentially (Equation 1.49, path a), in contrast to their normal behavior [47]. In the Ru-catalyzed version, the normal 1,4-diene is obtained (Equation 1.49, path b), which generates a very useful enol silyl ether with excellent chemo-, regio-, and diastereoselectivity [48]. 

In the case of the cyclic substrate 51, the intervention of a C-H insertion pathway reveals itself in terms of the diastereoselectivity, not regioselectivity. Thus, exposure of enyne 51 to the standard Ru catalyst at ambient temperature produced the transfused bicyclo[5.4.0]undecene 52 (Equation 1.60, path a) [55]. If a metallacycle mechanism was operative, coordination of the metal with both the alkene and alkyne must occur to form the cis-fused product. On the other hand, coordination of the Ru with the Lewis basic bridgehead substituent directs it to abstract an allylic C-H on the same face as the substituent, which then leads to the trans-fused product as observed. On the other hand, cycloisomerization using a Pd(0) precatalyst does indeed lead to the Z-fused bicycle (Equation 1.60, path b). 

Preparation of an useful synthon, the cyclic carbamate of L-daunosaminal (104), was achieved by sequential catalytic transformations of a key intermediate. Suitably protected propargyl diol 101, which was obtained by diastereoselective addition of allenyl stannate 99 to 0-benzyl (S)-lactyl aldehyde 100, was transformed as depicted in Scheme 18. Cycloisomerization to 3-deoxyglycal 103 was achieved by irradiation in the presence of tungsten hexacarbonyl, and subsequent nitrene insertion was catalyzed by rhodium acetate. Overall yield of the bicyclic daunosaminal (104) derivative from lactic acid derivative amounted to 44% [78]. 

Bisdiene 35 bears a complementary substitution pattern to that of 32b that is, the benzyl substituent resides adjacent to the methyl-bearing 1,3-diene moiety. Bisdiene 35 also cyclizes smoothly under the conditions employed for 32b and affords compound 36 in high yield (95%), and with good diastereoselectivity (>90% diastereomeric purity). Thus, bisdienes bearing an ester substituent undergo facile Pd-catalyzed cycloisomerization via a pathway that complements that found for substrates without the ester substituent. This defines a new bond construction that is inaccessible by classical... 

Inspired by the elegant approach developed by Stara, Stary, and coworkers (08JOC2074, 11EJ03849, 12AGE5857) for the synthesis of [ ]-heterohelicenes, Marinetti, Voituriez, and coworkers reported in 2014 the preparation of a new series of enantioenriched [6]-oxahelicenes 84 in which the terminal helical sequence ends with a phosphole oxide (14CC2199). The synthesis starts from the phosphindoles 82 and involves a metal-mediated diastereoselective [2+24-2] cycloisomerization of optically pure aromatic triynes 83 as a key step (Scheme 22). Under optimized... 

The Conia-ene reaction of P-ketoesters bearing a pendant triple bond involves the cycloisomerization of an enyne formed by enolization. This transformation is efficiently catalyzed by cationic gold(I) complexes and afforded cyclopentane derivatives with excellent yields and moderate to good diastereoselectivities (Scheme 4-40). Acetylenic silyl enol ethers or imines react in an analogous manner. By this method, iodoalkynes were converted into iodocyclopentenes, which are highly useful in natural product synthesis. 

As a further demonstration of the synthetic utility of this Cu(I)-catalyzed cycloisomerization methodology, the same group described its application for an expeditious and highly diastereoselective synthesis of ( )-monomorine 322 (Scheme 9.111) [291]. 

Gold-catalysed cycloisomerization of l,7-diyn-3,6-bis(propargyl carbonate)s provide for a diastereoselective synthesis of naphtho[ ]cyclobutenes by a cascade sequence involving gold-catalysed double [3,3]-rearrangement, 6 r-electrocyclic reaction, and a decarbonylative cyclization (Scheme 15). °... 

Chen, Z., Zhang, Y.-X., Wang, Y.-H., Zhu, L.-L., Liu, H., Li, X.-X., Guo, L. (2010). Gold catalyzed diastereoselective cascade allylation/enyne cycloisomerization to construct densely functionalized oxygen heterocycles. Organic Letters, 12, 3468-3471. 

Evans, P A., Baum, E. W. (2004). Diastereoselective intramolecular temporary silicon-tethered rhodium-catalyzed [4+4+2] cycloisomerization reactions regiospecific incorporation of substituted 1,3-butadienes. Journal of the American Chemical Society, 126, 11150-11151. 

Mainly because of the strong relativistic effect, exaltation of the % and a Lewis acidities of gold cations has been largely used over the past decade [31,32]. To begin with, a diastereoselective Au(in)-catalyzed 5-pjt -cycloisomerization of alkenynols 61 to enol ether 62 followed by an intermolecular Diels-Alder reaction was reported by Barluenga et al. for the preparation of the desired spiro adduct 63 (Scheme 9.17) [33]. The total diastereoselectivity observed could be explained by an endo-approach... 

---