Formylcyclopropanes

Scheme 31 Redox esterification of chiral enantioenriched formylcyclopropanes...

Chiral formylcyclopropanes.2 The oxazolidine (1), obtained by reaction of cinnamaldehyde with l>-( -)-ephedrine, reacts with diazomethane [Pd(OAc)2 catalysis] to give 2 in at least 90% ee. Hydrolysis of 2 to 3 is effected by moist SiO,. It is also possible to prepare cyclopropanes with three chiral centers, such as 5. 

MISCELLANEOUS REACTIONS OF DIHYDROPYRIDINES Additional tests for net hydride transfers initiated by single-electron transfer include the use of substrates in which such pathways would necessarily involve readily ring-opened cyclopropylmethyl or readily cyclized 5-hexenyl radicals. Products from these radical reactions are not formed in NAD+/ NADH dependent enzymic reductions or oxidations (Maclnnes et al., 1982, 1983 Laurie et al., 1986 Chung and Park, 1982). Such tests have also been applied in non-enzymic reductions. Thus cyclopropane rings in cyclopropyl 2-pyridyl ketones, or imines of formylcyclopropane (van Niel and Pandit, 1983, 1985 Meijer et al., 1984) survive Mg+2 catalysed reduction by BNAH or Hantzsch esters but are opened by treatment with tributylin hydride. 

Sohn SS, Bode JW (2006) A-Heterocyclic carbene catalyzed C-C bond cleavage in redox esterifications of chiral formylcyclopropanes. Angew Chem Int Ed 45 6021-6024... 

As is the case for oxycyclopropanes extra activation and extended product functionality is achieved by using sulphur-substituted cyclopropanes with a vicinal acceptor group. According to equation 116 synthesis of a variety of y-oxothioesters and j -oxoketene dithioacetals is possible. A formylcyclopropane of this type has been converted to a furan derivative " . Transformation of the carbonyl to a hydroxymethyl group and acid treatment allows preparation of dienes " ... 

Diethyl 2-Formylcyclopropane-l,l-dicarboxylate (Table 9, Entry 11) Single Procedure ... 

Dichlorocyclopropanes prepared from acetals of a,) -unsaturated alehydes are particularly useful intermediates since they alford, after hydrolysis, l,l-dichloro-2-formylcyclopropanes, which are not readily available by other routes (Table 15). 

For the synthesis of formyl-substituted cyclopropanes, acetal-substituted compounds, the functional equivalent of the formyl-substituted compounds, are employed. Either an acetal substituent is incorporated into the diazoalkane (e.g. 2,2-dimethoxy-l-diazoethane can be used ) or on the double bond. Here it provides sufficient activation for the addition step, as is seen in the synthesis of formylcyclopropane (31) and /ra .v-l,2-diformylcyclopropane (32). ... 

Tricarbonyliron complexes of conjugated trienes react with diazoalkanes at the free (uncom-plexed) double bond. In the synthesis of dimethyl 2-formylcyclopropane-l, 1-dicarboxylate (48), the ceric ion served the double function of catalyzing the deazetization and removing the tricarbonyl iron protecting group. When the optically active iron carbonyl complex was used, the addition of diazomethane gave selectively one diastereomer and this was used to make optically active dimethyl 2-formylcyclopropane-l,1-dicarboxylate (>90% ee). A similar route was employed to make the optically active formyl cyclopropanes 49, precursors to optically active cis- and tran.v-chrysanthemic acids. 

The largest and most useful group of these ring contractions are those of dihydrofurans (general formula A = carbon, B = oxygen). In this series, the equilibrium is more evenly balanced and, for example, when 2,3-dihydrofuran was equilibrated with formylcyclopropane (3) by passage through a hot silica tube (475-500°C) and the product fractionally distilled, it was claimed that a 40-50% yield of the cyclopropane could be isolated. 

The corresponding ring contractions of furans normally give cyclopropenyl products, but in some cases a cyclopropyl product is isolated. Hence, photolysis of 2-cyanofuran gave a mixture of stereoisomers of 3-alkoxy-2-formylcyclopropane-l-carbonitrile (14). ... 

Condensation of diethyl bromomalonate with diethyl 2-formylcyclopropane-l,l-dicarboxylate gave diethyl 2-[2,2-bis(ethoxycarbonyl)cyclopropyl]oxirane-2,2-dicarboxylate. ... 

Stoichioinetric deuterioformylation of bicyclo[2.2.1]hcpt-2-ene with cobalt tetracarbonyl deuteride gives the exo-product in only 20% yield122. Hydroformylation of substituted cyclo-propenes stereoselectively leads to formylcyclopropanes. Thus, 2,3-diphenyl-2-cyclopropene-carboxylic acid esters give exclusively the 2-formyl-2,3-diphenylcyclopropanecarboxylic acid esters with the aldehyde group cis to the ester group114,122. 

The synthesis of a novel cyclopropyl analog of arachidonic acid [7] via a convergent synthesis that employed methyl (lR,25)-2-formylcyclopropane-carboxylate in conjunction with the ylide from (3Z,6Z)-pentadeca-3,6-dienyl(triphenyl)-phosphonium iodide was reported (62). A new approach to cyclopropene fatty acids has been developed for the synthesis of methyl sterculate [8] and methyl 2-hydroxy-sterculate this involves the 1,2-deiodination of 1,2-diiodocyclopropanes with butyllithium at low temperature (63). The synthesis of deuterated cyclopropene fatty esters structurally related to palmitic and myristic acids has been reported (64). 

A domino Michael/a-alkylation reaction between bromoacetoacetates and a,fS-unsaturated aldehydes provides the 2-formylcyclopropane derivatives in high yields with excellent diastereoselectivity and up to 99% ee (for further details see Chapter 10) [37]. Similarly, an approach using enones 45 and bromonitromethane 46 has been used in organocatalytic nitro-cyclopropanation reaction to give 47 (Scheme 7.8)... 

In contrast to the use of the specific type of sulfur ylides and related compounds, the employment of readily available alkyl halides for a catalytic Michael-alkylation reaction with enals to produce the corresponding formal [2-1-1] cycloadducts is an extremely challenging task. As an example, Wang [82a] and Cordova [82b, 83a] independently reported the enantioselective organocatalytic reaction of bromoma-lonates 78 and enals, which led to the corresponding cyclopropanes 79. In both cases, chiral diarylprolinol trimethylsilyl ethers 8 and 80 were involved as catalysts, giving access to the corresponding 2-formylcyclopropane derivatives 79 in... 

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