C Wittig reactions

The Wittig reaction can be controlled to give a high percentage of the cis alkene. Young Gyu Kim of Seoul National University has shown (Tetrahedron Lett. 2004,45,3925) that addition of an excess of methanol to the -78°C Wittig reaction of 3 led to the complementary trans alkene 4. 

C. Wittig Reaction with Unstabilized Ylides Followed by Cyclization... 

Wadsworth-Emmons reaction (c/. Wittig reaction) between atoms 2 and 3, and final adjustments yielded ( )-maysine (16). 

Scheme 15 Beak s formal synthesis of (+)-lentiginosine (127) and (-)-2-ep/-lentigino-sine (128)J° Reagents (a) BHa-THF (b) Swern oxidation (c) Wittig reaction (d) TFA, CH2CI2, rt, 2 h (e) Fl2C=CFICOCI, K2CO3, TFIF, reflux, 24 h, (f) Grubbs II catalyst (6), CH2CI2, reflux, 24 h.

Wittig reaction The reaction between an alkyl-idene phosphorane, C = PR3 and an... 

Several structures of the transition state have been proposed (I. D. Williams, 1984 K. A. Jorgensen, 1987 E.J. Corey, 1990 C S. Takano, 1991). They are compatible with most data, such as the observed stereoselectivity, NMR measuiements (M.O. Finn, 1983), and X-ray structures of titanium complexes with tartaric acid derivatives (I.D. Williams, 1984). The models, e. g., Jorgensen s and Corey s, are, however, not compatible with each other. One may predict that there is no single dominant Sharpless transition state (as has been found in the similar case of the Wittig reaction see p. 29f.). 

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

The most attractive feature of the Wittig reaction is its regiospecificity The location of the double bond is never m doubt The double bond connects the carbon of the ongi nal C=0 group of the aldehyde or ketone and the negatively charged carbon of the yhde... 

The Corey process is also useful for the synthesis of PGs of the 1 and 3 series. Catalytic hydrogenation of (34) (see Fig. 5) with 5% Pd/C at — 15-20°C results in selective reduction of the 5,6-double bond. Subsequent transformations analogous to those in Figure 5 lead to PGE (9) and PGF (10). The key step for synthesis of the PG series is the Wittig reaction of (29) with the appropriate unsaturated CO-chain yUde (170). 

In the BASF synthesis, a Wittig reaction between two moles of phosphonium salt (vitamin A intermediate (24)) and C q dialdehyde (48) is the important synthetic step (9,28,29). Thermal isomerization affords all /ra/ j -P-carotene (Fig. 11). In an alternative preparation by Roche, vitamin A process streams can be used and in this scheme, retinol is carefully oxidized to retinal, and a second portion is converted to the C2Q phosphonium salt (49). These two halves are united using standard Wittig chemistry (8) (Fig. 12). 

The C.lOO-C.lOl diol group, protected as an acetonide, was stable to the Wittig reaction used to form the cis double bond at C.98-C.99 and to all of the conditions used in the buildup of segment C.99-C.115 to fully protected paly-toxin carboxylic acid (Figure 1,1). 

The enormous scope of the Wittig reaction and its variants in affording a smooth, high-yield synthesis of C=C double bonds, etc., has been amply delineated by the work of Wittig... 

The teal value of the Wittig reaction is that it yields a pure alkene of defined structure. The C=C bond in the product is always exactly where the OO group was in the reactant, and no alkene isomers (except E,Z isomers) are formed. For example, Wittig reaction of cyclohexanone with methylenetriphenyl-phosphorane yields only the single alkene product methylenecyclohexane. By contrast, addition of methylmagnesium bromide to cyclohexanone, followed by dehydration with POCI3, yields a roughly 9 1 mixture of two alkenes. 

Compound 16, the projected precursor of 15, could conceivably be assembled from bishomoallylic alcohol 17 via a pathway that features the oxidative functionalization of the A20,21 double bond with participation by the C-17 secondary hydroxyl. Compound 17 is an attractive retrosynthetic precursor for compound 16 because the A20-21 double bond, which could permit the introduction of the adjacent C-20 and C-21 stereocenters in 16, provides a convenient opportunity for significant molecular simplification. Thus, retrosynthetic cleavage of the A20 21 double bond in 17 furnishes compounds 18 and 19 as potential building blocks. The convergent union of the latter two compounds through a Wittig reaction would be expected to afford 17 stereoselectively. 

Intermediates 18 and 19 are comparable in complexity and complementary in reactivity. Treatment of a solution of phosphonium iodide 19 in DMSO at 25 °C with several equivalents of sodium hydride produces a deep red phosphorous ylide which couples smoothly with aldehyde 18 to give cis alkene 17 accompanied by 20 % of the undesired trans olefin (see Scheme 6a). This reaction is an example of the familiar Wittig reaction,17 a most powerful carbon-carbon bond forming process in organic synthesis. 

---