Enoates acyclic

Conjugate addition reactions of acyclic Midiael acceptors possessing betetoatom-SLibstituted stereogenic centers in tlieir )>-positions may provide usefiil levels of diastereoselectivity. A typical example is given witli tlie y-alkoxy-substituted enoate 49 in Sdieme 6.8 [17]. High levels of diastereoselectivity in favor of tlie anii addition product SO were found in tlie course of dlmediylcuprate addition. 

The use of nonstabilized carbon nucleophiles in this reaction has been rare. Recently, however, it was shown that lithium ester enolates participate in Pd-cata-lyzed 1,4-additions to cyclic and acyclic vinyloxiranes, affording the corresponding 6-hydroxy-4-enoates in good yields and with complete regioselectivity [117, 118]. 

Scheme 6.8. Diastereoselective addition of lithium dimethylcuprate to acyclic enoate 49 (TBDPS = t-butyidiphenylsilyl, BOM = benzyloxymethyl,...

Rifamycin S Scheme 6.9. Construction of the polypropionate segment of Rifamycin S through iterative diastereoselective cuprate addition to acyclic enoates. a) Me2CuLi, TMSCI,... 

A drawback of the Z enoates is usually lower reactivity, reflected in prolonged reaction times and higher reaction temperatures. This may be overcome by switching to more reactive enone systems. Thus, addition of the functionalized cyano-Gilman cuprate system 67 to Z enone 66 proceeded smoothly at low temperatures, with excellent acyclic stereocontrol at the /i-stereocenter [26, 27]. Stereocontrol upon... 

Tab. 6.4. Results of o-DPPB-direeled cuprate addition to acyclic enoates 127-131 (o-DPPB = ortTio-diphenylphosphinobenzoyl, Tr = triphenylmethyl, Piv = pivaloyl).

Systematic studies of organocuprate conjugate additions to three pairs of y-epimeric and geometrically isomeric y-chiral acyclic enones and enoates (159a,b) and (160a,b) have allowed one to generalize diastereofacial selectivity of these reactions (Scheme 20). 

Figure 3.32. Scope of Rh/(5)-binap-catalyzed as5tmmetric 1,4-addition of LiArB(OMe)3 to acyclic a,P-enoates.

Enol ethers 23 and 26 readily undergo cycloadditions with 2,/f-unsaturaled esters such as dimethyl fumarate (24) and methyl tran.v-but-2-enoate (27) giving cyclobutanes, 25 and 28 + 29, respectively, under mild conditions.8 It is interesting to note that the stereochemical integrity of the acyclic alkene is maintained in the cycloadducts. 

A stereoselectivity dependence on the cuprate was also reported in the -alkylation of y-substituted acyclic enoates (Scheme 17).101 The trans isomer (41) gave preferential formation of the anti isomer (42), regardless of the organocopper reagent employed. When the cis isomer (43) was treated with... 

With acyclic substrates such as (45), simple steric arguments are a suitable rationale for the observed stereoselectivity.851 For example, in the reaction of PI1CU-BF3 with enoate (45), acid (46) was obtained, after hydrolysis, in 99.5% ee. This preference is consistent with an attack of the reagent from the least sterically encumbered side of the carbon-carbon double bond (shown by the arrow equation 49). 

Acyclic dienes, in Ru and Os half-sandwich j6-arenes, 6, 540 Acyclic enoates, diastereoselective additions, 9, 516 Acyclic enones... 

In the metal-free epoxidation of enones and enoates, practically useful yields and enantioselectivity have been achieved by using catalysts based on chiral electrophilic ketones, peptides, and chiral phase-transfer agents. (E)-configured acyclic enones are comparatively easy substrates that can be converted to enantiomeri-cally highly enriched epoxides by all three methods. Currently, chiral ketones/ dioxiranes constitute the only catalyst system that enables asymmetric and metal-free epoxidation of (E)-enoates. There seems to be no metal-free method for efficient asymmetric epoxidation of achiral (Z)-enones. Exocyclic (E)-enones have been epoxidized with excellent ee using either phase-transfer catalysis or polyamino acids. In contrast, generation of enantiopure epoxides from normal endocyclic... 

Scheme 10. Working hypothesis for the o-DPPB group to act as an organometallic reagent directing group for the conjugate addition of Gilman cuprates to acyclic enoates.

The last results reported in this field are related to the 1,3-dipolar reactions of tert-butyl ( )-4,4-diethoxy-2-p-tolylsulfinylbut-2-enoate and (S5,Ss) and (R5,Ss) 5-ethoxy-3-p-tolylsulfinylfuranones (42a and 42b) with different nitrile oxides [ 167]. Acyclic sulfoxides react with benzonitrile, acetonitrile, and bromo-formonitrile oxides to yield isoxazoles resulting in desulfinylation from the adducts. Cyclic dipolarophiles afford bicyclic isoxazolines in their reactions with benzonitrile oxide. The reactivity of the double bond as a dipolarophile is strongly increased by the sulfinyl group. The regioselectivity of these reactions... 

Due to their high conformational flexibility, chiral acyclic Michael acceptors often display low diastereofacial selectivities in copper-mediated conjugate addition reactions.80 Nevertheless, acceptable levels of diastereoselection can be obtained, in particular with heteroatom-substituted Michael acceptors. For example, treatment of the y-benzyloxymethyl-substituted enoate 100 with lithium dimethylcuprate in the presence of chlorotrimethylsilane gives the anti-adduct 101 with excellent diastereoselectivity (Scheme 26). a Products of this type can be easily... 

Intramolecular conjugate addition naturally results in ring formation. The body of examples of this type of reaction is subdivided into the Sections 4.7.1.1.2.1. Acyclic Acceptors and 4.7.1.1.2.2. Cyclic Acceptors , depending on whether or not the accepting enone/enoate moiety is part of a ring system. In the latter case, the cyclization affords a bi- or oligocyclic product. The steric restrictions thus imposed reduce the number of thermodynamically feasible products. As a consquence, product structures can usually be predicted easily, and high stereoselectivities are observed. 

Recently, reactions of acyclic vinyl epoxides have attracted increased attention. In many cases, regio-selectivity is strongly dependent upon substrate structure, with ( )- and (Z)-isomers providing different results. Similarly, stereoselectivity is the result of a complex interplay of steric and conformational effects, but anti addition to an s-trans conformation appears to be preferred. The regio- and stereo-selective ot-alkylation of "y,8-epoxy-a,p-enoates has been reported recently. Again, Sn2 selectivity was greater with cyanocuprates than with the harder homocuprates, but in no case was conjugate addition detected. 

Cyclopropanation reactions with alkyl 2-diazobut-3-enoates (entries 3-6) occur with a remarkably high diastereoselectivity. When 1,3-dienes (acyclic 1,3-dienes,cyclopen-tadiene, furan, " substituted pyrroles ) are cyclopropanated with these reagents, the CK-divinylcyclopropane derivatives are formed with high or complete diastereoselectivity, but they usually undergo a spontaneous Cope rearrangement under the reaction conditions. 

The first synthesis modelled on biomimetic lines was directed to obtaining anacardic acids by way of polyketides [237] and later to a (17 l)-orsellinic acid [43]. A less complicated approach based on the Michael addition of ethyl acetoacetate and ethyl octadec-2-enoate, has led to a C15 orsellinic acid, Fig (4)-56, 2,4-dihydroxy-6n-pentadecylbenzoic, considered to be the biogenetic precursor of the cashew phenols [238], notably cardol, by decarboxylation. The use of bromine at the aromatisation stage in this synthesis precluded the extension of the method to components with unsaturated side-chains, although bromination with copper(ii)bromide and thermal debromination offers an alternative procedure. In a more recent approach, by the use of an oxazole intermediate and its addition to ethyl acetoacetate, (15 0) and (15 1) anacardic acid have been obtained [239] as shown in Scheme 5a, b. The 8(Z),1 l(Z)-diene and 8(Z),1 l(Z),14-triene have also been synthesised [240] by way of ethyl 6-(7-formylheptyl)-2-methoxybenzoate (C), prepared from acyclic sources, rather than, as in previous work, by semisynthesis from the ozonisation of urushiol. 

Reduction of a, -unsaturated carbonyl compounds (6, 491 492). The final paper has now been published. In general, )3-5ubstituted cyclohexenones undergo exclusive 1,4-reduction with either Selectride. Acyclic enones generally undergo 1,2-reduction to allylic alcohols. The Selectrides are particularly useful for 1,4-reduction of enoates. Super-Hydride (lithium triethylborohydride) is less useful for this purpose. Unfortunately L-Selectride reduces o./S-acetylenic esters only to propargylic alcohols. 

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