Wittig olefination Z-selective

The possibility of synthesizing pure (Z)-olefins by means of reactive salt-free ylides predestinates the (Z)-double bond at C-5 in e.g. 106 and 107 to be introduced into the corresponding aldehyde via the Wittig reaction. The ( )-configurated double bond at C-13 (105,106 and 107) with its vicinal hydroxy group was frequently formed by the phosphonate method (cf. Chapter 2). In some cases, however, it could also be obtained by ( )-selective Wittig olefination using resonance-stabilized phosphoranes. 

Triol 984 is converted to the 6-membered benzylidene acetal 1009 with benzaldehyde and PTSA, and the remaining hydroxyl group is then oxidized to an aldehyde (1010) under Swem conditions. A Z-selective Wittig reaction provides a separable mixture of 1011 and its E-isomer (92 8). The stereochemical outcome of the Wittig reaction is strongly dependent on the nature of the alkoxyaldehyde and the polarity of the solvent. In this case polar solvents favor the formation of the Z-olefin, methanol being optimum. Treatment of 1011 with acetic acid gives the desired butenolide 1012 in nearly quantitative yield. 

In our work with aminolysis of vinylepoxides (see Section 9.2.1.1), the substrates were routinely synthesized by SAE followed by Swern/Wittig reactions (Table 9.3, Entries 1-4) [48, 49]. This procedure is well suited for terminal olefins, but dis-ubstituted olefins can seldom be obtained with useful (E Z) selectivities. Nakata recently synthesized some advanced intermediates towards natural products in this manner (Entries 5, 6) [50, 51]. 

Peterson olefination, a silicon variant of the Wittig reaction, has been used to convert a-silyl benzyl carbamates (78) into trisubstituted vinyl carbamates (79) in moderate-to-good yields and with some ii/Z-selectivity. ... 

Because the geometry of the 9-double bond was not clear at that time, Corey et al. 75> tried to prepare the (Z)-9-isomer as well as the ( )-9-isomer of leukotriene-A (78 and 86). In the synthesis of the former isomer the tribenzoyl derivative of D-(—)-ribose (79) was converted in 8 stepy into the optically active epoxyaldehyde 71 and the latter to 72. 72 was olefmated with ylide 82, generated by treatment of the corresponding phosphonium mesylate with lithium diisopropylamide in THF/ HMPA75) (Scheme 15). In the first olefination step 72+82- 78, however, similar to the first method, a A9-isomer mixture was formed. The loss of (Z)-selectivity of the Wittig reaction is due to the use of conjugated unsaturated, i.e. moderate ylides of type 82, and had to be expected because of the mechanism of the Wittig reaction (see Sect. 2). 

The selective reduction of the 8-hydroxy- 3-keto ester 4 with Me4NBH(OAc)3 afforded the corresponding l,3-anft -diol in 87% yield and 14 1 diastereoselectiv-ity. The 1,3-anti -diol was protected as the acetonide 5, followed by a Pd-catalyzed coupling reaction with the vinyl iodide 6 to provide the diene 7 in 69% yield. Reduction of the ester, Swem oxidation, and finally, Wittig olefination afforded the (Z)-vinyl iodide 8. 

The reaction of p-chlorobenzaldehyde with phenyldiazomethane in the presence of (MeOlsP and catalytic amounts of meso-tetraphenylporphyrin iron chloride (ClFeTPP) resulted in the formation of the corresponding alkenes with an /Z-selectivity of 86 14, but the yield was low (30%). When phenyldiazomethane is generated in situ from the corresponding potassium tosylhydrazone salt, the olefin yield increases to 92% with E/Z-selectivity of 97 3. Thus, high levels of -selectivity are obtained with semistabilized ylides by this method . This process is applied to a wide range of aldehydes and is practical as compared to standard Wittig reaction, and therefore finds applications in industry, o... 

The mixture was taken on further, and the PMB ether removed to form the corresponding diol (Scheme 16). After selective oxidation of the primary hydroxyl with IBX, a Wittig olefination was used to form the C13-C14 bond, completing the carbon skeleton of myriaporone 4. Once the (Z)-olefm was installed, the two diastereomers 45a and 45b were now easily separated and each diastereomer was taken on independently. 

The synthetic route to 619 is a rather lengthy 27-step sequence outlined in Scheme 87 [192]. The first key reaction is a Wittig olefination of 606 with phosphorane 620 to give 621 with > 98% Z-selectivity. Subsequent Claisen rearrangement of the free alcohol 622 provides 623 with >98% stereoselectivity. Dieckmann condensation followed by decarboxylation gives the thermodynamically more stable ran -cyclopentanone 624 trans cis ratio = 7 1). 

Model studies of the Wittig olefination of hydrocinnamaldehyde were undertaken with phosphonium iodides derived from 1397. These results indicated the best ElZ ratios were obtained with a tributylphosphonium salt," using an excess of n-BuLi. These conditions were modified slightly and then applied to 1404 (Scheme 1.359). Thus 1404 and 1405 were treated with LiHMDS in DMF to produce 1406a in excellent yield with 9 1 E/Z selectivity. A two-step sequence converted 1406a to the aldehyde 1406b. 

Secondly, Wittig-type olefination involving a-halomethyltri-phenylphosphoranes can afford the desired alkenyl halides in moderate to good yields with good stereoselectivities favoring the Z-isomer (eq 4). However, phosphonium salts suffer from tedious preparation and the triphenylphosphine oxide by-product can be hard to remove from the final product. The >Z-selectivity can also be poor, as observed in the Cassiol total synthesis (eq 5). ... 

Farwick and Helmchen [28] prolonged the alkyl chain of chiral allylamines by a hydroformylation-(Wittig olefination) sequence (Scheme 5.139). Particular attention was paid to the choice of the JV-protective group. As expected in the Wittig olefination step, mainly the Z-configured olefins were formed. After selective removal of only one Af-protective group, the obtained Af-Boc protected methyl esters were converted via a diastereoselective aza-Michael reaction into the corresponding fi-proline derivatives. 

The cobalt(II) porphyrin complex (CoTPP) has been found to be an efficient catalyst for the Wittig type olefination of acyl phosphonates (96) with ethyl diazoacetate (EDA) in the presence of triphenylphosphine (Seheme 32). ° In a one pot reaction under mild conditions, highly functionalized vinyl phosphonates (97) could be obtained in high yields (72-92%) and high E/Z selectivities (95/5-100/0), in relatively short reaction times. 

The role of steric interactions on anomalous stereoselectivity in the Wittig reaction has been examined. " DFT calculations combined with a distortion/interaction energy analysis show that the anomalous Z selectivity observed in Wittig reactions of o-substituted benzaldehydes is not caused by phosphorus-heteroatom interactions in the addition transition state but is predominantly steric in nature. The calculations reproduced correctly the stereoselectivity preferences for a wide range of reactant pairs as well as relative reactivities for different substituent types. An efficient synthesis of olefins by the coupling of stabilized, semi-stabilized, and non-stabilized phosphorus ylides with various carbonyl compounds in the presence of silver carbonate has been reported. Wittig olefination of aromatic, heteroaromatic, and aliphatic aldehydes (yields up to 97%) and a ketone (yield 42%) was demonstrated. 

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