Stereoselective alkylation

An Index to types of reactions, e.g. alkylations, stereoselective reductions, cyclizations etc. and... 

Hydroxyazetidin-2-ones can be oxidised efficiently to azetidine-2,3-diones by P205 in DMSO <00JPR585>, and then the 3-carbonyl group can be alkylated stereoselectively by application of the Baylis-Hillman reaction <99TL7537> or by use of substituted propargyl bromides to provide densely functionalized 3-hydroxy-P-lactams . 

The addition of an allyl metal to a-amino aldehydes has been used by Vara Prasad and Rich (Scheme 12)J23l After the addition step, the allyl group is oxidized to a carboxylic acid and lactonized. Then, the a-carbon of the lactone is alkylated stereoselectively. These investigators also systematically examined the addition reaction to determine its diastereo-selectivity. The highest diastereoselectivity was obtained when allyltrimethylsilane was used in the presence of tin(IV) chloride. An increase in the steric bulk of the protecting group and of the side chain also resulted in a better diastereoselection. Alternatively, Taddei and co-workers 24-26 used a 2-(halomethyl)allylsilane and the side chains were introduced by nucleophilic substitution of the halogen (Scheme 13). 

It is clear, nonetheless, that successful dearomatising cyclisations are not confined to systems which can undergo electrocyclic ring closure 456 for example cyclises to 457, which may be protonated or alkylated stereoselectively.201 Without the oxazoline substituent, similar reactions lead to rearomatisation. 

An oxazoline auxiliary has been used to alkylate stereoselectively and regioselectively isoindoline at the a- and a -positions to produce the C2-symmetric amine (12), as shown in Scheme 23. ... 

Alkylation of fahydroxy carboxylic esters (8, 258). Dianions of / -hydroxy carboxylic esters (LDA, —50° to —20°) are alkylated stereoselectively to give mainly f/irao-compounds (equation I). The alkylation of dianions of a-mono-... 

In this style too, asymmetry has become a major concern.42 An asymmetric version 147 of this homoenolate was made from natural nor-ephedrine and could be alkylated stereoselectively using lithium tetramethylpiperidide (LiTMP) as base. The product could be hydrolysed to the bicyclic amide43 149. 

In the case of (17), Collum and Clardy were able to obtain some osmometric data about aggregation in solution. They found that (17) in THF had an apparent molecular weight of 515, which corresponds to a 3.5 degree of aggregation. Based on these results, and the independence of axial alkylation stereoselectivity with respect to the concentration of (17) or the nature of the metal ion and solvent, Collum and Clardy suggested that solvent free tetramers of (17) may be the predominant species in solution. Studies... 

Alkylation of chiral enolates (Section 20.12) Chiral enolates may undergo alkylation stereoselectively to give product enriched in one enantiomer. 

A Shapiro reaction reduces the ketone 74 into the allylic alcohol 75. After Jones oxidation, the y-lactone 76 is alkylated stereoselectively at Cll to give the target molecule 65. 

Several bi- and tri-cyclic thiepan derivatives were obtained by autoxidation of the cyclobutadiene (111) or by various reactions with strained sulphur-containing acetylenes, e.g.. the dithiet (112). The ylides derived from cis- and trans-ill) were alkylated stereoselectively at low temperatures, and they reacted with carbonyl compounds to give ring-opened oxirans (113). Reduction of the 6-methoxy-carbonyl derivative of (72) afforded the ten-membered cyclic sulphide (114). ... 

An added advantage of this approach is that lactone 23 can be alkylated stereoselectively with lithium isopropylcyclohexyl amide and methyl iodide to give which was converted in several steps to 21 containing stereochemistry analogous to that present in gibberellic acid. 

P.M. Khan, R. Wu, K.S. Bisht, Pd(0) catalyzed intramolecular alkylation stereoselective synthesis of furan and isoxazoline-2-oxide analogs. Tetrahedron 63 (2007) 1116-1126. 

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