Three-carbon synthons

A few examples of reactivity transfer through more than three carbon atoms are also known (a -synthon N. Miyaura, 1975, 1976). 

Acylbenzotriazoles 162 are efficient C-acylation reagents for the regioselective conversion of ketone enolates into P-diketones . Diethyl(l-benzotriazolmethyl)phosphinate (163) was found to be a convenient reagent for the stereoselective preparation of (E)-l-(l-alkenyl)benzotriazoles <00SC1413>. The novel three-carbon synthon 1-(1//-133-... 

Methyl deoxypodocarpate 127 (Scheme 1) 129) represents a simple problem since the ketone 132 is well-known and readily available from Hagemann s ester in three steps. The problem of geminal alkylation of this ketone stems from its existence as an EjZ mixture of ring fusion isomers. Recognizing that decarbonylation of aldehydes occurs readily with Wilkinson s catalyst creates a structural equivalence of an acetaldehyde chain and a methyl group as in 128. This simple relationship immediately establishes several options, a simple one uses a thioacetal such as 129 as a synthon for the aldehyde. The presence of a carbonyl group three carbons away... 

Heterocycles.—The phosphonium salt (59) is an effective three-carbon synthon, as demonstrated by its reaction with enolates of /9-keto-esters (Scheme 20) to give cyclopentenyl sulphides via an intramolecular Wittig reaction.63 Ylides are also intermediates in the synthesis of dihydrofurans (60) from the cyclopropylphos-phonium salt (61) and sodium carboxylates (Scheme 21).64 Cumulated ylides are very useful for the synthesis of heterocyclic compounds, e.g. (62), from molecules which contain both an acidic Y—H bond and a carbonyl or nitroso-function, as shown in Scheme 22.65... 

G. Casiraghi, L. Colombo, G. Rassu, and P. Spanu, Synthesis of enantiomerically pure 2,3-dideoxy-hept-2-enono-1,4-lactone derivatives via diastereoselective addition of 2-(trimethyl-siloxy)furan to D-glyceraldehyde and D-serinal-based three-carbon synthons, Tetrahedron Lett. 30 5325 (1989). 

Ketenedithioacetals (1) can formally be considered as S.S-dialkylated dithioacids. However, their reactivity pattern is quite different from that displayed by compounds like dithioacids and dithioesters bearing a thiocarbonyl group, and their syntheses and properties are usually treated apart. The review by Kolb [59] and its 254 references give access to most of the literature in the field (see also [60]). a-Oxoketenedithioacetals (2) are particularly versatile compounds as three-carbon synthons in organic synthesis, and some reviews deal specifically with them [61, 62]. Many efficient procedures are available for their syntheses [59, 61], and number of these make use of the reactions of carbon disulfide with carbanionic species followed by alkylation at the sulfur atoms (see [63] and [64] for the reactions of CS2). 

The retrosynthetic disconnection for the y-keto acid shown below generates an acyl anion synthon and a three-carbon carbocation. 

These adverse conditions have elicited considerable efforts to reduce the number of chiral centers as well as hydroxyl groups with the simultaneous introduction of useful functional groups (10, 13-15). One approach involves the shortening of the aldose carbon chain, or, more simply, its bisection, as exemplified by the use of D-mannitol-derived 2,3-Oisopropylidene-D-glyceraldehyde. Whilst this product and its L-ascorbic acid-derived enantiomer have developed into popular enantiopure three-carbon synthons (16), it may be objected that the photosynthetic achievement of Nature which graciously provides us with six-carbon compounds, is utilized rather inefficiently, clearly pointing towards elaboration of synthons from sugars with retention of the carbon chain. 

S,.S)-Bissetone (28), when traced back to building block 27, only lacks the 3-carbon branch, i. e. acetone. Indeed, the lithium enolate of acetone proved to be a suitable three-carbon synthon attacking the carbonyl function with a 4 1 preference from the proaxial side (27 -> 30). The benzoyl group shift directly following the attack elaborates the desired 2-oxopropyl-branehed tetrahydro-pyranone 31, the dibenzoate of bissetone in fact, from which the parent compound is generated simply by de-O-benzoylation (48) ... 

General Three Carbon Chiral Synthons from Carbohydrates Chiral Pool and Chiral Auxiliary Approaches... 

Scheme III/9. Cyclopropene as a three-carbon atom synthon [61].

When we consider the synthesis of a quinoline, the obvious disconnections are, first, the C-N bond in the pyridine ring and, then, the C-C bond that joins the side chain to the benzene ring. We will need a three-carbon (C3) synthon, electrophilic at both ends, which will yield two double bonds after incorporation. The obvious choice is a 1,3-dicarbonyl compound. 0... 

Examples of such three-carbon synthons are 2-nitro-2-propen-l-yl acetates and piva-lates, which have been developed by Seebach and coworkers57,58 as reagents for [3 + 3] cyclizations with cyclic and acyclic ketone enamines. After workup these reactions give 4-nitrocyclohexanones. With enamines from prolinol methyl ether and cyclic ketones, enantiomerically pure compounds were obtained58. An example of such a [3 + 3] cyclization is the synthesis of bicyclic nitroketone 99 from nitroallylic ester 97 and enamine 98 (equation 18). 

Construction of the Cyclopropane Ring from Three-Carbon Synthons. 114... 

The reactions presented in this chapter are divided into three groups deoxy-genative processes employing two-carbon and one-carbon synthons (Sect. 2), reactions employing three-carbon synthons (Sect. 3) and miscellaneous syntheses, involving indirect zirconium assistance (Sect. 4). 

The title transformation provides an alternative pathway for the construction of the cyclopropane ring from a synthon of three carbons. The intramolecular cyclization of homoenolate anion equivalents is represented in Scheme 11, Eq. (ii). In practice, several routes involving metals such as Mg, Zn, and Ti, as well as different homoenolate precursors, have been developed [17a-e]. 

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