Enals a-branched

The Yamamoto vinylogous aldol reaction, in which bulky aluminium-based Lewis acids activate the aldehyde and also become part of the enolate, is stereodirected by 2,3-syn and 2,3-anti disubstitution of the aldehydes bulky -substituents favour 1,3-syn diol formation, whereas alkynyl groups lead to 1,3-anti products. The reaction of (g) a-branched enals with isatins may switch from vinylogous aldolization to a pericyclic pathway depending on the nature of the a-branch. °... 

Scheme 43.22 Cooperative organocatalysis for the asymruetric y-alkylation of a-branched enals.

The impossibility of a conjugated alkene in 15 as well as 13, makes this an exceptional case in aldols of aldehydes. Without the branch at the a-carbon, the product is more usually a conjugated enal.6 So the linear isomer 17 of 16 with the same base gives the enal 18 in good yield.7 The true product of the dimerisation is the anion 19. This is in equilibrium with the enolate that allows an ElcB elimination of water 20 to give the enal 18. 

Branched enals have been aziridinated enantioselectively using a diaryl prolinol TMS ether as catalyst, giving IV-tosyl aziridines with a quaternary centre." ... 

Scheme 42.14 Organocatalytic MCRs of a-branched a,p-unsaturated aldehyde enals by way of an iminium ion/enamine sequence Friedel-Crafts/amination strategy and sulfa-Michael/ amination strategy. Protocol point all substrates added at the outset of the reaction.

Z)-awh-4-Hydroxy-l-aIkenyl carbamates 363, when subjected to substrate-directed, vanadyl-catalysed epoxidation , lead to diastereomerically pure epoxides of type 364 (equation 99)247,252,269 qqjggg epoxides are highly reactive in the presence of Lewis or Brpnsted acids to form -hydroxylactol ethers 366 in some cases the intermediate lactol carbamates 365 could be isolated . However, most epoxides 364 survive purification by silica gel chromatography . The asymmetric homoaldol reaction, coupled with directed epoxidation, and solvolysis rapidly leads to high stereochemical complexity. Some examples are collected in equation 99. The furanosides 368 and 370, readily available from (/f)-0-benzyl lactaldehyde via the corresponding enol carbamates 367 and 369, respectively, have been employed in a short synthesis of the key intermediates of the Kinoshita rifamycin S synthesis . 1,5-Dienyl carbamates such as 371, obtained from 2-substituted enals, provide a facile access to branched carbohydrate analogues . 

By far the most important compounds of this type are the a,/ -unsaturated aldehydes and ketones, of which the simplest general representation is (8) and (9) respectively. Branching may be present at either or both of the a- or p- positions as for example in 2-ethylhex-2-enal (10) and 4-methylpent-3-en-2-one (11). Compounds where the carbon-carbon double bond is terminal are acraldehyde [(8), R=H], and the alkyl (or aryl) vinyl ketones [(9), R = H, R = alkyl, aryl etc.]. 

The chiral titanated bislactim ether 104 undergoes 1,2-addition to a,(3-unsaturated aldehydes. With enal 105, it gives adduct 106, the epoxidation and subsequent hydrolysis of which forms the branched-chain amino-acid derivative 107 [84] (Scheme 13.42). 

Undec-lO-enal is a widely employed synthetic aroma compound with a citrus, waxy, fatty odor accompanied by a green, soapy nuance. It can be produced by hydroformylation of 1,9-decadiene (Scheme 6.25). The required substrate is accessible, for example, by olefin disproportionation of cyclooctene with ethylene [100]. The diene was reacted with syngas in the presence of a heterogenized Rh catalyst in a flow reactor to give undec-lO-enal and 2-methyldec-9-enal in 80% overall yield and a slight dominance of the linear aldehyde. The isomers could be separated by distillation. The smell of the branched aldehyde is very similar to that of... 

Radical reactions have been further utilised in the construction of branched-chain sugars. Unsaturated iodide (24) with allyltributyltin or Bu3SnH and methyl acrylate has afforded the doubly-branched derivatives (25) and (26) by way of intra- and then inter-molecular radical processes. Similarly, bromide (27) gave the 3-C-allyl derivative (28) which, after transformation into enal (29), underwent a further radical cyclisation (Scheme... 

The base-promoted rearrangements of alkenes (60) and (62) has selectively afforded branched-chain derivatives (61) and (63) (Scheme 4). A route to pyranoside conjugated enals is mentioned... 

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