Cram cyclic model

Cram s open-chain model 229 Cram s rule 229, 233 Cram chelate model 229 Cram cyclic model 229 Cram-Felkin-Anh model 191,207, 236 f 246 cubane 12,318 cyanoacetic acid 636 f. cyanohydrin, protected 145, 150 f. cyclic carbonate protection 541 f., 657, 659 f., 666, 670 cyclization -,6-endo 734 -, 5-exo 733 f. 

Threo diastereoselectivity is consistent with a chelation-controlled (Cram cyclic model) organolithium addition (Figure 8a). Since five-membered chelation of lithium is tenuous, an alternative six-membered chelate involving the dimethylamino nitrogen atom of the thermodynamically less stable (Z)-hydrazone (in equilibrium with the ( )-isomer) cannot be discounted. The trityl ether (entry 4, Table 9) eliminates the chelation effect of the oxygen atom such that the erythro diastereomer predominates (via normal Felkin-Ahn addition) (Figure 8b). 

The reaction of a-ketoesters with the tin (II) enolate of IV-acetyl-thiazolidinethione 1.123 (R=R1=H, X = S) has been earned out with an excellent enantioselectivity in the presence of chiral amine 2.13 (Figure 6.88). The reactions of a- or P-alkoxyaldehydes with metal enolates may or not be under chelation control (Cram cyclic model, 1.4.2). Reetz has shown that triisopropoxy- or tris-diethylaminotitanium enolates display a sufficiently weak Lewis acidity so as to avoid chelation control [408],... 

Another example presented by this group involved the reduction of ( )-3-hydroxy-5-phenyl-2-pentanone with Sml2 in the presence of ethyl crotonate to afford jjn-y-lactone in excellent yield and diastereoselectivity at three contiguous stereocenters (Scheme 6) [19, 20], Cram cyclic model K was used to explain the selectivity in the formation of the first new stereogenic center. Subsequent coordination of the ethyl crotonate ester group to the Sm" was responsible for the facial selectivity during the formation of the second center [20]. 

The presence of an a-alkoxy substituent does not always lead to Cram selectivity. Reduction of 262a gave 82% of the syn diastereomer, 263.2 Analysis of the Cram cyclic model for 262 (see 264) leads to an incorrect prediction of the anti-diastereomer (265) as the major product. The normal Cram model (see 262b) predicts the correct syn-diastereomer (263) but in reality, the solution to this problem requires that the alkoxy substituent at the C3 position be coordinated with the metal of the reducing agent. In 264, a five-membered... 

The use of ( S)-HYTRA (645) produces the mixture of 647 and 648 in an 87 13 ratio, whereas (R)-HYTRA (646) reverses the selectivity to favor the anti isomer 648 syn anti ratio = 8 92). At first glance, predominant formation of the anti isomer appears to violate the Cram cyclic model for chelation controlled conditions. However, the stereochemical outcome of this reaction is determined by reagent control rather than substrate control, which means that the diastereoselectivity is governed by the chirality of the HYTRA rather than 632. 

Chiral 3,5,6-trihydroxyheptanoic acids are potentially useful intermediates for the synthesis of natural products. The backbone can be constructed by a titanium-mediated aldol reaction of silyl enol ether 536 with 929. The syn adduct 949 is formed exclusively, as predicted by the chelation-controlled Cram cyclic model. 

The addition of benzylmagnesium chloride to 130 at —78 °C is strongly influenced by chelation of the a-hydroxy center with the magnesium cation diastereofacial selectivity consistent with the Cram cyclic model therefore results in a 66% yield of the syn isomer 131 only. Interestingly, and for reasons not quite clear, the addition of allylmagnesium chloride proceeds with high diastereoselectivity to provide the anti isomer 133 as the major diaster-eomer (Scheme 31) [37]. 

The observed very high l,2-lk induction of the sto eocenter present in the side chain oi the imine upon the C4 stereocenter of the azetidinone may be rationalized via a Cram cyclic model by assuming coplanarity between oxygen and nitrogen atom of the imine due to chelation of lithium cation so that the nucleophile attacks from the less hindered diastereotopic face. 

These opposite diastereoselectivities were explained by assuming a Felkin-Anh-Houk model (anti addition) and a proton-bridged Cram cyclic model (syn addition) for the case of differentially protected a-amino aldehydes (7) and (8). The resulting... 

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