Allenylmetal reagents

Most of the synthetic routes to allenes utilize the reaction of propargylic compounds as electrophiles. In contrast, if the propargylic compounds serve as nucleophiles, a wide variety of substituted allenes, which are not easily accessible by the reaction of propargylic compounds with nucleophiles, are available. However, in order to synthesize enantioenriched allenes by this method, it is necessary to generate configurationally stable propargyl or allenylmetal reagents (cf. Chapter 9). 

Scheme 9.3 Transition states for additions of allenylmetal reagents to aldehydes.

The configurational stability of chiral allenylmetal reagents depends to a large extent on the nature of the metal substituent. The mechanism of the racemization process has not been studied in detail, but two reasonable pathways can be proposed, based on known reactivity characteristics of these compounds. The first entails reversible intermolecular SE- rearrangement to the propargylic isomer. This process could proceed by a pure syn or anti pathway, in which case no racemization would take place. However, the occurrence of both pathways would result in racemization (Scheme 9.5). 

Using (/ ,/ )-Diop as the chiral auxiliary, the amount of chiral induction is not dependent on the temperature, but depends on the type of chiral ligand in the palladium complex and on the allenylmetal reagent. When magnesium or copper is present, a reversal of the configuration... 

The same authors have also reported the direct preparation of (3-chlorovinyl alcohols (I, Fig. 10) by the coupling reaction of enantiopure 4-oxoazetidine-2-carbaldehydes with a variety of propynyl-, and allenylmetal reagents [265]. 

In the following Sections we review the reactions of chiral allylmetal and allenylmetal reagents and their application to the synthesis of complex natural products. These reagents are useful for the enantioselective allylation of achiral aldehydes... 

Marshall s chiral allenylmetal reagents have been utilized in double asymmetric reactions with chiral aldehydes for the synthesis of polypropionate natural products. All four dipropionate diastereomers are accessible from the reactions of chiral allenylmetal reagents with a-chiraI-y5-alkoxy aldehydes 97 (153, 158, 276, 277]. The BF3-OEt2-catalyzed addition of allylstannane (l )-218a to aldehyde 97a occurs in high yield and diastereoselectivity to give the xyn.syn-dipropionate 395, presumably through either the synclinal or antiperiplanar Felkin transition states 396 and 397 (Eq. (11.31)). 

Marshall has applied the chiral allenylmetal reagents in a number of natural product syntheses [154, 278-280]. The synthetic utility of these reagents is maximized when the alkyne functionality of Marshall s products is used to further elaborate the carbon skeleton of the ultimate synthetic target. This methodology is il-... 

This synthesis illustrates the potential of chiral allenylmetal reagents for the synthesis of this polyketide natural product. 

The additions of chiral nonracemic allenylmetal reagents to chiral a-methyl propanal derivatives have been proven useful for the assembly of polypropionate fragments. These reagents rely on allene chirality to favor one of the two possible diastereomeric transition states in the addition and, thus, differ in a fundamental way from the aforementioned methods in which a chiral auxiliary or catalyst provides the control element. For example, a chiral allenylstannane 246 is added to a chiral aldehyde (S)-230, derived from the Roche ester, in the presence of various Lewis acid promoters to afford any of the four diastereo-mers with excellent diastereo- and enantioselectivity, depending on the reaction conditions. Representative results are depicted in Scheme 10.48. From the stereocontrol point of view, these transformations follow Cram-fike open transition state models without or with chelation, respectively. If InBr3, SnCLi, BuaSnCl, or other additives... 

Marshall JA, Grant CMJ. Preparation of chiral allenylmetal reagents from enantioenriched allenyl iodides and propar-gyUc mesylates. A comparison of indium, bismuth, and tin derivatives. Org. Chem 1999 64 8214-8219. 

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