Reactions with Induced Diastereoselectivity

4 GPa and 50 °C. At 20 °C the reaction did not take place, and even in the presence of Lewis acids such as Eu(hfc)3, TiCU or ZnCl2 the expected cycloaddition did not occur. 

4 GPa and 40 °C. Thus, a pressure-induced diastereoselectivity does not exist in this reaction. 

Chiral 2-nitro-l-sulfinylalkenes undergo a. [4+ 2] cycloaddition with cyclopentadiene either in the presence of a Lewis acid or under high pressure of 800 MPa at room temperature as described by Fuji et al. [63]. In both cases complete diastereoselectivity was observed with (Z)-sulfinyl compounds such as 132 in contrast, only low diastereoselectivity was found when using the corresponding ( )-sulfinyl 

A large increase in the conversion rate with increasing pressure was observed which corresponds to the well-known fact that Diels-Alder reactions have a strong negative activation volume AV. Following El yanov s equation [66] the differences in the activation volumes AAV were determined from the plot of 

P (CPa) Yield (%) Ratio o/ diastereomers endo Itendo lltexo Itexo II 

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Chromium aminocarbenes [39] are readily available from the reaction of K2Cr(CO)5 with iminium chlorides [40] or amides and trimethylsilyl chloride [41]. Those from formamides (H on carbene carbon) readily underwent photoreaction with a variety of imines to produce /J-lactams, while those having R-groups (e.g.,Me) on the carbene carbon produced little or no /J-lactam products [13]. The dibenzylaminocarbene complex underwent reaction with high diastereoselectivity (Table 4). As previously observed, cyclic, optically active imines produced /J-lactams with high enantioselectivity, while acyclic, optically active imines induced little asymmetry. An intramolecular version produced an unusual anti-Bredt lactam rather than the expected /J-lactam (Eq. 8) [44]. 

Freparatively useful induced diastereoselectivities have been reported mainly for 1,1-di-substituted allyllithium derivatives which bear carbanion-stabilizing substituents. l-[Methyl-thio-l-(trimethylsilyl)-2-propenyl]lithium106 and the appropriate 1-phenylthio107 derivative, generated from the allylic sulfide with sec-butyllithium, in the reaction with tetrahydropyranyl-protected pregnolone, furnish a single diastereomer. 

The reactions of 2-propenyltitanium reagents with chiral aldehydes (0) or ketones ( and ) usually exhibit enhanced induced diastereoselectivities compared to allyl Grignard reagents. This enhanced diastereoselection is mainly attributed to the greater bulk and lower reactivity of the reagent. Some examples are collected ( )52. 

Very high levels of induced diastereoselectivity are also achieved in the reaction of aldehydes with the titanium enolate of (5)-l-rerr-butyldimethylsiloxy-1-cyclohexyl-2-butanone47. This chiral ketone reagent is deprotonated with lithium diisopropylamide, transmetalated by the addition of triisopropyloxytitunium chloride, and finally added to an aldehyde. High diastereoselectivities are obtained when excess of the titanium reagent (> 2 mol equiv) is used which prevents interference by the lithium salt formed in the transmetalation procedure. Under carefully optimized conditions, diastereomeric ratios of the adducts range from 70 1 to >100 1. 

Furthermore, both (E)- and (Z)-enolborinates add to aldehydes in a stereoconvergcnt manner, giving predominantly, syn-/J-hydroxycarbonyl compounds49. In contrast, only moderate induced diastereoselectivity is obtained in the reaction of achiral aldehydes with C2-symmetric enolborates, whereby the chiral information is located in the ligand at the metal atom50. The ee of the product /1-hydroxy ketones ranges from 4 to 72%. 

A decisive improvement in the stereoselective performance of the Ugi reaction was achieved by the use of 1-ferrocenylalkylamines, in particular, l-ferrocenyl-2-methylpropylamine. as the inducing chiral auxiliary 18, S7. The iminc formed from the (/ )-enantiomer and isobutyralde-hyde reacts at — 78 °C with tm-butyl isocyanidc and benzoic acid to give the (S )-valine derivative with a diastereoselectivity of about 100 1. 

The optically active a-sulfinyl vinylphosphonate 122 prepared in two different ways (Scheme 38) is an interesting reagent for asymmetric synthesis [80]. This substrate is an asymmetric dienophile and Michael acceptor [80a]. In the Diels-Alder reaction with cyclopentadiene leading to 123, the endo/exo selectivity and the asymmetry induced by the sulfinyl group have been examined in various experimental conditions. The influence of Lewis acid catalysts (which also increase the dienophilic reactivity) appears to be important. The 1,4-addition of ethanethiol gives 124 with a moderate diastereoselectivity. 

Moreover, a dramatic increase of the reaction rate was observed when the coupUng of aromatic imines mediated by samariiun diiodide was carried out in the presence of both water and a tertiary amine or tetramethylethylene-diamine (TMEDA) [29], causing the almost instantaneous formation of the 1,2-diamine, although with undetermined diastereoselectivity. Similarly, the samarium diiodide promoted reductive coupling of iminiiun ions formed in situ by reacting ahphatic aldehydes with secondary amines and benzotriazole occurred at temperatures as low as - 70 °C [30]. Even in this case a mixture of diastereomers with undetermined ratio was obtained nevertheless, the item of diastereoselectivity induced by a chiral amine (auxiliary) is worthy of investigation. 

The diastereoselective ultrasonically induced zinc-copper 1,4-addition of alkyl iodides to chiral a, (i-unsaturaied systems in aqueous media was studied by Suares and co-workers the Z-isomer gives good diastereos-electivities while reactions with the E-isomer are nonstereoselective.63 The 1,4-addition to chiral y, a-dioxolanyl-a, (i-unsaturated esters also proceeds with good yields (51-99%) (Eq.10.29).64... 

As examples of the influence of a stereogenic center in the aldehydes used on the induced diastereoselectivity, the reactions of 2-763a-d with 2-746 to give the dihy-dropyrans 2-764a-d were investigated. Moreover, the reactions show that the trans-cycloadducts are formed almost exclusively using aliphatic aldehydes (Scheme 2.168). 

In Scheme 14 the effect of pressure on Diels-Alder reactions with acyclic heterodienophiles or heterodienes is presented. The application of high pressure leads also in these reactions to an enhancement of rates and improvement of yields. The hetero-Diels-Alder reaction (entry 3) is a good example of the interplay between pressure and temperature. At high pressure the rate of reaction as well as the diastereoselectivity are increased. The pressure-induced acceleration allows the temperature of reaction to be lowered, which leads to a further increase of diastereoselectivity. 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

Z)-4-[(5)-2,2-Dimethyl-l,3-dioxolan -ylmethylene]-2-phenyl-5(47/)-oxazolone 632 can react as a dienophile in diastereoselective Diels-Alder reactions. Thus, 632 undergoes a thermally induced Diels-Alder reaction with cyclic dienes, for example, cyclopentadiene and cyclohexadiene, to afford a mixture of the four... 

Thus, in the example of the chiral olefin 3, there is simple diastereoselectivity of (m4a + m4b)/(m4c + m4d) and induced diastereoselectivities of m4a/m4b and m4c/m4d. It is not strictly necessary, but conversely there is no harm, in applying the term simple diastcrcosclcc-tivity to the first case, i.e., to a diastereoselective reaction of achiral reactants. In this volume the presentation of a given reaction type always begins with simple diastereoselectivity of achiral reactants. 

An interesting 1,2-induced diastereoselective allylation is that of 2-aryl-3-methylbutenolide 33 with allyl bromide24. This reaction is worth noting, in the sense that the enolate was formed with sodium hydride and the reaction temperature never went below 0°C, although the yield and diastereoselectivity were still very good, Although lactone 33 is a special case with its a-aryl substituent, it does seem that very low temperatures are not always really necessary. 

Section A.5). Indeed, three enantiomeric pairs of 2-oxazolidinones have been commercially available since 1991. Enantiomerically pure 4-phenyl-2-oxazolidinone has likewise been prepared from / -aminobenzeneethanol (phenylglycinol)64. Base-catalyzed acylation of the enantiomerically pure 2-oxazolidinones with an appropriate acyl chloride gives the desired 3-acyl-2-oxazolidinones 3, 6 and 9 which have been used extensively in highly diastereoselective reactions of various types such as alkylations, aldol reactions (see Section D.l.3.4.2.4), hydrox-ylations (see Section D.4.1), aminations (see Section D.7.1) and Diels-Alder reactions (see Section D. 1.6.1.6) alkylation giving products with induced chirality in the a-position. 

If two different external electrophiles are to be added to the dimetallic species, diastere-oselectivity can only be achieved if the two carbon-metal bonds are properly discriminated against the reaction with a first electrophile. Moreover, the resulting monometallic species has to exhibit significant configurational stability. Coordination by a heteroatom, which turned out to be essential for achieving substrate-induced diastereoselection, also nicely served these purposes. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

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