Non-chelation control

Noyori "Open" Transition State for non-Chelation Control Aldols... 

SCHEME 23. Non-chelate controlled addition of l-bromo-l-hthioalkene 164 to O-protected lac-taldehydes 162. Introduction of an umpoled formyl d synthon CHO... 

A stereochemical behavior similar to that of the 1-bromo-l-lithio aUcene 164 with regard to chiral aldehydes is shown by the hthiated methoxyallene 183. When added to iV,iV-dibenzylated a-aminoaldehydes 188, it reacts with non-chelate control so that awh -carbinols 189 are obtained predominantly. Diastereomeric ratios of 189 190 range from 80 20 to 95 5. As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium f-butoxide and subsequent acid hydrolysis" . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, A-protected a-hydroxy-/3-amino esters 194/195 result (Scheme 25)"" . 

M. T. Reetz, Chelation or non-chelation control in addition reactions of chiral a- and (3-alkoxy carbonyl compounds, Angew. Chem. Int. Ed. Engl 23 556 (1984). 

Boron trifluoride, zinc bromide, and tin tetrachloride led to non-chelation-controlled antt -adducts 3, whereas the use of titanium tetrachloride and magnesium bromide resulted in chelation-controlled syn-adducts 2. Both adducts can be used as starting compounds for the iterative synthesis of amino sugars. 

N-Monoprotected aldehydes reacted according to the non-chelation-controlled model. The best diastereocontrol (syn/anti, 20.6 1) was achieved with allyltrimethylsilane in the presence of tin tetrachloride. A similar method was used in the synthesis of the aminoglycosidic fragment of calicheamycin yj [36]. 

Braun, M. Mahler, H. Non-chelate-controlled addition of 1-bromo-l-lifhio-l-alkenes to... 

Chelation or Non-chelation Control in Addition Reactions of Chiral a and B-Alkoxy Carbonyl Compounds"... 

The diastereoselectivity for the reaction of 157, which possesses a 2-methyl-1,3-dioxolanyl group, with enolates generated from fert-butyl acetate was found to be highly dependent on the reaction conditions.89 For example, the lithium enolate gave (Ss,S)-158 (72% de) while the titanium enolate afforded (Ss,/ )-158 (92% de). A non-chelation-controlled transition state was used to explain the preferential formation of (Ss,S)-158 while a six-membered chairlike transition state containing a four-membered metallocycle and/or a seven-membered counterpart was proposed for the formation of the (Ss,R)-158. Treatment of (Ss,S)-158 with TFA gave P-amino acid 159 in 70% yield. 

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]. 

The relative rate increase with LiC104 (3 mol %) in CH2CI2 was also observed in a case involving the aldolization of A jA -dibenzyl-protected aminoaldehyde, where anti-product predominates, as a result of non-chelation control. When attempted in Et20, the transformation is successful only when 5.0 m LPDE is used. Moreover, a reaction time of 18 h at room temperature sufficed for complete conversion of iso-butyraldehyde, while reacting less rapidly to the desirable product [108]. 

Grieco et al. have demonstrated that an ethereal solution of LiClO4 is useful for the diastereoselective HDA reaction of Danishefsky s diene 102 with a-amino aldehydes by chelation and non-chelation control (Scheme 10.110) [296]. According to a report by Reetz et al., a catalytic amount of LiClO4 suspended in f J I. Gf, efficiently promotes similar reactions with aldehydes and imines [297]. 

The diastereoselectivity of the allylation of a-benzyloxy aldehyde 23 was studied70 (equation 64). It was found that under chelation control a very high percentage of the syn adduct is formed whereas under non-chelation control the anti product is favored. 

Typical Non-chelation-Controlled Reactions of N,N-Dibenzylamino Aldehydes Me3SiO-... 

A high degree of stereoselectivity can be achieved in chelation-controlled reactions, utilizing hydroxy groups as stereodirectors (Eq. 59) [69], Studies have revealed that non-chelation-controlled processes may also proceed with enhanced selectivities, and this led to the synthesis of the cA-decalin skeleton of vinigrol (Eq. 60) [70]. 

Alternatively, we surmised that the lactone 14 could be converted to Weinreb amide 40, which provided additional options for generation of the homoallylic alcohol 42. For example, through the influence of an a-alkoxy group, homoallylic alcohol 42 could be obtained by either a chelation-controlled reduction of p,y-unsaturated ketone 41 or a non-chelation-controlled allylation of 13 (Scheme 14). Thus, elaboration of lactone 35 into amide 40 began by treatment of 35 with N,0-hydroxylamine hydrochloride in the presence of trimethylaluminum to give the amide 39 in 93% yield. Further, protection of the revealed... 

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