Chelate-controlled carbonyl addition reactions

Ketone 13 possesses the requisite structural features for an a-chelation-controlled carbonyl addition reaction.9-11 Treatment of 13 with 3-methyl-3-butenylmagnesium bromide leads, through the intermediacy of a five-membered chelate, to the formation of intermediate 12 together with a small amount of the C-12 epimer. The degree of stereoselectivity (ca. 50 1 in favor of the desired compound 12) exhibited in this substrate-stereocontrolled addition reaction is exceptional. It is instructive to note that sequential treatment of lactone 14 with 3-methyl-3-butenylmagnesium bromide and tert-butyldimethylsilyl chloride, followed by exposure of the resultant ketone to methylmagnesium bromide, produces the C-12 epimer of intermediate 12 with the same 50 1 stereoselectivity. 

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

M. T. Reetz, Structural, Mechanistic, and Theoretical Aspects of Chelation-Controlled Carbonyl Addition Reactions, Ace. Chem. Res. 1993, 26, 462M68. 

Usefid reviews address alkyl zirconocene catalysts for the pol)mierisation of silanes to poly silanes by a a-bond metathesis mechanism, chiral titanates as promoters in aldol reactions, and MeTiCl3 as a reagent for chelate-controlled carbonyl addition reactions. 5 xhe reactions of terminally functionalized alkenes with zirconocene hydrides are reviewed. Thermochemical studies show that while the bond dissociation enthalpies of Zr—C6H13 and Zr— CgHjj in zirconocene systems are comparable, the insertion of cyclohexene into the Zr—bond is more exothermic than the insertion of hexene. 

Reetz MT. Strucmral, mechanistic, and theoretical aspects of chelation-controlled carbonyl addition reactions. Acc. Chem. Res. 1993 26 462 8. 

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). 

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

LiC104 was shown to be a more compatible Lewis acid for chelation in an ethereal solvent—when TiCU, a typical chelation agent for a-alkoxyaldehydes, was used in EtaO for alkylation of 79, moderate diastereoselectivity (68 32) was obtained. Rapid injection NMR studies of the TiCU-promoted chelation-controlled Mukaiyama aldol reaction and the Sakurai reaction show that an acyclic transition state must be involved in which the silyl groups never reach the carbonyl oxygen atom. In LPDE-mediated enolsilane additions silylated products predominate. Obviously, the mechanism is different—it is a group-transfer aldol reaction [107]. 

Angew Int 23 556 (1984) (chelation and non-cheladon control in addition reactions of chiral - and / -alkoxy carbonyl compounds) 30 49 (1991) (enandoselectivity)... 

Another factor that affects stereoselectivity of carbonyl addition reactions is chelation If an a or p substiment can form a chelate with a metal ion involving the carbonyl oxygen, the stereoselectivity is usually governed by the chelated conformation. Complexation between a donor substituent, the carbonyl oxygen, and the Lewis acid can establish a preferred conformation for the reactant, which then controls reduction. Usually hydride is delivered from the less sterically hindered face of the chelate. 

The Kishi synthesis ot monensin teatures allylic conformational analysis to predict stereochemistry of hydroboratlon-oxidations in acyclic systems. The Still synthesis features acyclic diastereoselection in carbonyl addition reactions (chelation control and Felkin-Ahn control). 

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