Chiral alkoxy-allenes

ReiSig and Hausherr synthesized (-)-preussin in ten steps starting from L-fructose. The chiral alkoxy allene 143 was formed as a mixture of diastereoisomers which differed in the configuration of the chiral axis [77]. 

Chiral alkoxy allenes derived from 1,3-alkylidene-L-erythritol and -D-threitol have been used in cycloaddition reactions to provide the 4-substituted /3-lactams 418 (R = Me, Ph). Intramolecular alkylation at nitrogen was achieved by the action of potassium carbonate and tetrabutylammonium bromide in dry acetonitrile. The absolute stereochemistry of the product 419 (R = Me, Ph) was assigned on the basis of the CD helicity rule (see Section 2.04.3.5) and NMR spectroscopy. The [2+2] cycloaddition of CSI to threitol vinyl ethers was found to have low stereoselectivity in contrast to the findings with erythritol derivatives <2004CH414, 2005EJ0429>. 

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

The first investigations in the 1960s [11,12] established the base-induced isomerization of alkyne precursors as the most practical and general route for the synthesis of alkoxy-and aryloxyallenes. In the meantime, a number of monosubstituted allenes 8 bearing an achiral or a chiral group R is smoothly accessible by this efficient procedure (Scheme 8.5) [1, 2,13-19]. Beside the most commonly used base potassium tert-butoxide, other bases, e.g. n-butyllithium, are also applicable for this isomerization. Recently, the yields of alkyne-allene isomerizations could be significantly increased, in particular with aryloxy-substituted allenes, by using microwave irradiation (Eq. 8.1) [20]. 

More recently, lithiated allenes with chiral a-alkoxy groups have been generated and added to aldehydes as well as to a tosylimine with substantial diastereoselec-tivity. 

Various reactions of pronucleophiles with allenes has been reviewed by Yamamoto and Radhakrishnan [18]. Regioselectivity in these reactions is controlled by steric and electronic effects. The attack at C-3 is a main path, but several exceptional cases have been reported. Due to electronic bias, the hydrocarbonation of alkoxy- or phenoxyallenes 70 gives allylic ethers as the C-1 adduct 72 either exclusively or predominantly via 7r-allylpalladium 71 [19]. Trost expanded the regioselective formation of allylic ether to an asymmetric reaction. Addition of the Meldrum s acid 74 to the allenyl ether 73 catalyzed by palladium trifluoroacetate and (5, 5)-XIII-l as a chiral ligand in the presence of trifluoroacetic acid afforded the the allylic ether 75 with 99 % ee in 75 % yield [20]. 

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