Donor-Substituted Allenes

Modem Allene Chemistry. Edited by N. Krause and A.S.K. Hashmi Copyright 2004 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30671-4 

Several reviews on various aspects of the chemistry of these allenes have been published [1-10] and therefore this chapter concentrates on the presentation of principle reaction patterns, on important applications of known processes and on new developments in this area. 

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In this chapter we shall deal with donor-substituted allenes of type 3, 4, 5 and 6 (Scheme 8.2), among which oxygen-substituted allene derivatives 3 are of major importance. They have been utilized for numerous syntheses of interestingly func-... 

Due to the synthetic versatility of donor-substituted allenes, it is of great importance to modify these compounds by substitution reactions at C-l. The CH-acidity at the a-carbon of alkoxyallenes allows their smooth lithiation [12, 42] which conveniently... 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

Saalfrank, Hoffmann and co-workers performed a number of reactions with tetra-alkoxyallenes such as 196 (Scheme 8.47) [1, 41, 105, 114—116] and demonstrated that this class of donor-substituted allenes can serve as a 1,3-dianion equivalent of malonic acid. Treatment of 196 with cyclopropyldicarboxylic acid dichloride 197 produces 2,4-dioxo-3,4-dihydro-2H-pyran 198 through release of two molecules of ethyl chloride [115]. Similarily, the reaction of this allene 196 with oxalyl chloride gives 3-chloromalonic acid anhydride derivative 199. This intermediate is a reactive dieno-phile which accepts 2,3-dimethyl-l,3-butadiene in a subsequent [4+2] cycloaddition to afford cycloadduct 200 in good yield [116]. 

In general, sulfur-substituted allenes are accessible starting from alkyne precursors by a variety of transformations such as isomerization, rearrangement or addition reactions. The standard method for the synthesis of donor-substituted allenes is again the base-induced isomerization of alkynes. This very first method was applied for the preparation of achiral [11, 162, 163] and chiral [164] S-functionalized 1,2-dienes (Scheme 8.78). 

Sulfur-containing acyclic and cyclic compounds have been prepared from allenyl sulfides in numerous transformations such as substitutions, additions, cydoaddi-tions and other cyclization reactions. Like the other donor-substituted allenes, allenyl sulfides are suitable substrates for regioselective lithiation and substitutions as exemplified in Scheme 8.86 [168, 169,175]. 

The examples illustrated in the almost 100 schemes in this chapter demonstrate how versatile donor-substituted allenes can be in synthetic processes. The major applications concern addition reactions and cycloadditions to the allenic double bonds, which furnish products with valuable functional groups. Of particular interest are metalations - usually at C-l of the allene unit - followed by reactions with electrophiles that deliver compounds which can often be used for cyclization reactions. A variety of highly substituted and functionalized heterocycles arises from these flexible methods, which cannot be obtained by other reactions. Many of these transformations proceed with good regioselectivity and excellent stereoselection. 

So far, axially chiral donor-substituted allenes have rarely been used although they should be capable of transferring their stereochemical information to a new center of chirality. This lack may be due to the difficulties of generating axially chiral donor-substituted allenes with high enantiomeric purity. We expect that this gap will be filled in near future. 

The straightforward generation of lithiated allenes [31], in particular lithiated donor-substituted allenes [32], has opened up smooth and efficient routes to further metallated functionalized allenes. By transmetallation, metals such as magnesium,... 

Additional examples of palladium-catalyzed cross-couplings, in particular with allenylzinc compounds, can be found elsewhere [11, 15, 36]. A systematic study comparing several chiral palladium phosphine catalysts in the reaction of 4,4-di-methyl-1,2-pentadienylzinc chloride and iodobenzene revealed that an enantiomeric excess of only 25% was obtained from the best catalyst combination PdCl2 and (R,R)-DIOP [15]. The synthetic value of these transformations of donor-substituted allenes as precursors is documented by the preparation of a/l-unsaturatcd carbonyl... 

In spite of these first successful results, so far Stille cross-couplings have rarely reported employing functionalized stannylated allenes such as easily available donor-substituted allene 80a or allenyl esters such as 81 (Scheme 14.19) [19, 41, 42]. A single palladium-catalyzed annulation reaction with 80b as precursor leading to an a-pyrone derivative was reported [43],... 

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