Aldehydes a-heteroatom-substituted

The diastereoselectivity is observed in the Henry reaction using optical active niti o compounds or a-heteroatom substituted aldehydes. Lor example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-niti opropionate in the presence of neubal alumina leads to a mixture of three niti o-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

Several detailed studies of reactions of achiral aiiylboronates and chiral aldehydes have been reported4,52 - 57. Diastereofacial selectivity in the reactions of 2-(2-propenyl)- or 2-(2-butenyl-4,4,5,5-tetramethyl-l,3,2-dioxaborolanes with x-methyl branched chiral aldehydes are summarized in Table 252, 53, while results of reactions with a-heteroatom-substituted aldehydes are summarized in Table 34,52d 54- 57. 

Aldehydes bearing a-hetero substituents also typically afford anti products, and the general solution to syn selective a-heteroatom substituted aldehyde-aldehyde aldol processes via enamine catalysis also still remains to be discovered. Nevertheless, the anti process is remarkably useful because a variety of highly substituted aldehydes can be accessed in a single operation using only very inexpensive catalysts, such as proline 6 or the phenylalanine-derived imidazohdinone 46 (Scheme 21) [114, 116, 117, 119-121, 188]. 

There are a few reports of hetero-Diels-Alder Reactions promoted by LPDE. Intriguing stereoselectivity is observed for the [4 + 2] cyclization between Danishefsky s diene 77 and a-heteroatom-substituted aldehydes. For example, reaction of 77 with N-Boc-protected a-aminoaldehyde with 76 gave the threo isomer selectively, a result in keeping with a chelation-controUed process. In contrast, the threo diastereoselectivity observed could be reversed by changing the amino protecting group from A-Boc to A,A(-dibenzyl. In this instance, the erythro isomer was generated exclusively via a non-chelation-controlled transition state (Sch. 38) [89]. 

Hoffmann (with aldehydes 55a,c and d), Mulzner (with aldehyde 55b) and Wuts (with aldehyde 55e) subsequently reported similar findings in the crotylation reactions of a-heteroatom-substituted aldehydes with the ( )- and (Z)-crotylmetal reagents (Tables 11-3 and 11-4) [68-70]. These data, together with the results summarized in Table 11-2, clearly demonstrate that steric effects play a larger role in determining reaction diastereoselectivity than do. stereoelectronic effects. 

Stereoelectronic effects and nonbonded interactions are non-cooperative in the reactions of (E)-allylboronates and x-heteroatom-substituted aldehydes. Thus, while transition state 8 experiences the fewest nonbonded interactions (gauche pentane type, to the extent that X has a lower steric requirement than R3), transition state 9 is expected to benefit from favorable stereoelectronic activation (Felkin-type)58f. This perhaps explains why the reaction of 2,3-[iso-propylidenebis(oxy)]propanal and ( >2-butenylboronate proceeds with a modest preference (55%) by way ol transition state 9. This result is probably a special case, how ever, since C-3 of 2.3-[isopropylidenebis(oxy)]propanal is not very stcrically demanding in 9 owing to the acetonide unit that ties back the oxygen substituent, thereby minimizing interactions with the... 

A DFT study of enolborane addition of o -heteroatom-substituted aldehydes has focused on the relevance of the Cornforth and polar Felkin-Anh (PKA) models for asymmetric induction.154 Using chiral substrates, MeCH(X)CHO, polar (X = F, Cl, (g) OMe) and less polar (X = SMe, NMe2, PMe2) substituents have been examined. The former favour Cornforth TS structures, the latter PKA. TS preferences have been correlated with the relative energy of the corresponding rotamer of the uncomplexed aldehyde. An in-depth study of addition of ( > and (Z)-enolborane nucleophiles to 2-methoxypropanal successfully predicts experimentally determined diastereofacial selectivities. 

Several examples are presented in Table 15 which indicate that a-heteroatom substitution is compatible with this reagent. The tremendous advantage of the trifluoroethyl phosphonate reagent is the selective formation of (Z>alkene with aromatic aldehydes, while the trimethyl phosphonate gives the normal selectivity. 

A few systematic comparisons can be made for the reactions of simple aldehydes with a-heteroatom-substituted ylides. The normal Z-selectivity pattern of the PhjP CHX series decreases from X = iodine to bromine to chlorine or fluorine (Table 21, entries. 44-57). There may be a similar decrease in selectivity with decreasing atomic number from a-sulfide to a-ether substituents (compare entries 40-43 with 35-37). Unfortunately, no direct comparisons have been made, and there are very few examples involving reactions of simple aliphatic aldehydes RCH2CHO with either the a-alkoxy or the a-alkylthio ylides. It is too early for detailed generalizations, but the... 

The main stereoselective MBFTs for the synthesis of spirocyclic acetals or aminals involve the activation of a C-C triple bond to form an intermediate cyclic enol ether. The method disclosed above for the synthesis of a-heteroatom-substituted spirocen-ter (see Section 9.3.3, Scheme 9.18) [34] was next extended by the same authors to the synthesis of spiroacetals. They simply used salicyladehyde as starting aldehyde, but the transformation was not diastereoselective anymore [43]. This problem of stereoselectivity was recently solved by Gong and coworkers, who employed a gold(I)/chiral Brpnsted acid catalysis to do so [44], The chroman spiroacetals were obtained in excellent yields (67-97%) and with high stereoselectivities (up to 95% ee, up to 25 1 dr) (Scheme 9.24). This reaction resulted in the formation of three new single bonds and two stereogenic centers. 

Chromium(II) chloride also mediates Wittig-type reactions of a-heteroatom-substituted gem-dihalides and aldehydes. In Scheme 5.27, representative examples of the preparation of alkenylboranes [38], -silanes [39], and -stannanes [40] are shown. In each case, high -selectivity was observed. As these compounds are very important substrates for Suzuki, Hiyama, and Stille couplings, their stereoselective formation enhances the value of the chromium(II) chloride mediated reactions. 

Discuss the factors behind selection of the reactive conformation in the Felkin-Ahn model for conversion of 53 to 54. How would Cornforth have rationalized this stereochemical result [For an interesting system where the Cornforth and Felkin-Ahn models predict different stereochemical results see Evans, D. A. Siska, S. J. Cee, V. J. Resurrecting the Cornforth Model for Carbonyl Addition Studies on the Origin of 1,2-Asymmetric Induction in Enolate Additions to Heteroatom-Substituted Aldehydes Andrew. Chem. Int. Ed. 2003, 42, 1761-1765] (CJH-5)... 

The addition of a-hetero-substituted aldehydes to disulfones 72 was examined by Quintard and Alexakis [72]. The presence of a heteroatom in the cx-position of the aldehyde funchon increases the acidity of the hydrogen in the enolizable position and thus enhances the reactivity of the donor. a-Chloroaldehyde 89 gave excellent results in terms of yield and enantioselectivity using aminal catalyst 90 and offered a wide diversity of postfunctionaUzations of adduct 91 that take... 

In most of the successful Diels-Alder reactions reported, dienes containing no heteroatom have been employed, and enantioselective Diels-Alder reactions of multiply heteroatom-substituted dienes, e.g. Danishefsky s diene, are rare, despite their tremendous potential usefulness in complex molecular synthesis. Rawal and coworkers have reported that the Cr(III)-salen complex 15 is a suitable catalyst for the reaction of a-substituted a,/ -unsubstituted aldehydes with l-amino-3-siloxy dienes [21] (Scheme 1.28, Table 1.12). The counter-ion of the catalyst is important and good results are obtained in the reaction using the catalyst paired with the SbFg anion. 

Just as N for a nucleophile can be determined from a plot of log k against E for a series of electrophiles, in principle, the value of E for an electrophile can be determined from the intercept (at E + N = 0) of a plot of log (k/s) versus N for a series of nucleophiles (or indeed, if need be, from the measurement for a single nucleophile). In this way E values have been determined for many electrophiles other than benzhydryl cations, including metal-coordinated cations,186 BF3-coordinated aldehydes,274 tropylium ions, and many benzylic-and heteroatom-substituted carbocations. In the low reactivity range... 

A number of resonance stabilized or heteroatom substituted carbanions have been converted into titanium analogs for the purpose of testing chemoselectivity, e.g., Equation 12 21,77). Generally, an in situ reaction mode was chosen. In all cases a high degree of aldehyde-preference was noted. 

Heteroatom-substituted carbohydrates are efficiently assembled by the enzymatic aldol condensation of DHAP with an appropriately appended aldehyde. Iminocyclitols that are inhibitors of glycosidases, such as deoxynojirimycin and deoxymannojirimycin, are simply prepared by condensation of azo-substituted aldehydes under the FDP protocol followed by dephosphorylation and palladium mediated reductive animation (Scheme 5.18a).39 In addition a number of polyhydroxylated pyrrolidines that are efficient glucosidase inhibitors have been synthesized by this chemo-enzymatic strategy (Scheme 5.18 ).1" 30,40 If the palladium mediated hydrogenation is done in the presence of hydrochloric acid, an amino-sugar intermediate is formed as its hydrochloride salt. Treatment with base then forms polyhydroxylated imines, instead of iminocyclitols (Scheme 5.19).41... 

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