Julia-Lythgoe synthesis

Fig. 4.40. Second step of the Julia-Lythgoe synthesis of trans-alkenes (first step cf. Figure 11.22) stereoconver-gent reduction of the sulfonyl-acetates syn- and anti-k to the uniformly configured alkene trans-C. The sequence starts with an E2 elimination yielding the alkenylsulfone f-B (mecha-nistical details as given), which is followed by the reduction to the final product (mechanistic analysis cf. Figure 17.85)...

Fig. 4.37. Julia-Lythgoe synthesis of tram-olefins involving a HetVHet2 elimination.

The reductive elimination of (3-hydroxysulfones is the final step in the Julia-Lythgoe alkene synthesis (see Section 2.4.3).301 The (3-hydroxysulfones are normally obtained by an aldol addition. 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

The Julia-Lythgoe olefination has already been addressed twice as an important C=C double bond-forming two- or three-step synthesis of trans-alkenes (trans-B in Figure 17.85). The step... 

The strategy described here should find considerable use as a method for the stereoselective synthesis of alkenes. Although this olefination strategy involves one more step than the classic Wittig reaction, in many cases it may prove to be the more practical method. Finally, the scope, overall efficiency, and stereoselectivity of the 0-lactone route compares favorably to the Wittig, Julia-Lythgoe, and related established strategies for the synthesis of tri- and tetrasubstituted alkenes. 

The modified Julia-Lythgoe alkenation known as Julia-Kocienski alkenation is one-step synthesis of alkenes from benzothiazol-2-yl sulfones (RCH2SO2BT) 4.59 and aldehydes, which is an alternative procedure that leads to the alkene in one step and offers very good -selectivity. 

The stereoselective synthesis of alkenyl halides is also possible via Julia-Lythgoe alkenation. The other two methods for the preparation of alkenyl halides - Wittig reaction (using... 

Satoh, T., Yamada, N., Asano, T. Ligand exchange reaction of sulfoxides in organic synthesis sulfoxide version of the Julia-Lythgoe olefination. Tetrahedron Lett. 1998, 39, 6935-6938. 

Among the different methods for the formation of C-C double bonds, the reductive elimination of (3-functionalized (mainly P-hydroxy or (3-carboxy) sulfones, is one of the most widely used ones in organic synthesis. The reductive elimination of (3-hydroxy sulfones and derivatives is the so-called Julia,94 or Julia-Lythgoe olefination reaction (Eq. 2). It usually involves a condensation between the anion of an alkyl sulfone and a carbonyl compound to afford a (3-hydroxy sulfone (Eq. 47). The metal alkoxide intermediate is typically transformed in situ into a carboxylic or sulfonic ester derivative, which is then reduced... 

Reductive Eliminations in the Synthesis of Natural Products Synthesis of (—)-Siccanin. The Julia-Lythgoe olefination provides an important tool in the total synthesis of a number of natural products.12 The reductive... 

Application of the deoxygenation process to ff-hydroxysulfides or P-hydroxysulfones results in the clean formation of ra j-olefins through ji-elimination of a thiyl or sulfonyl radical [17]. This mild, radical version of the Julia olefin synthesis, initially described by Lythgoe and Waterhouse [17a], has been applied by two groups in the total synthesis of (+)-pseudomonic acid C. The transformation shown in Scheme 9 is taken from the synthesis by Williams and coworkers [17b]. 

Juglone = 5-hydroxy-l,4-naphthalenedione dienophile in tetracycline synthesis, 318 Julia-Lythgoe olefination, 34 Julia s terpenoid synthesis, 69-70 Juvenile hormone synth. steps, 20, 30, 135, 155... 

Samarium iodide can also be used as an alternative to sodium/ mercury amalgam for the reductive elimination of 1,2-acetoxy-sulfones in the Julia-Lythgoe olefination. The alkene is generated in a two-step process that first involves DBU or LDA treatment to generate a vinyl sulfone that is then reductively cleaved with samarium iodide (eq 44). The diastereoselectivity of both transformations is usually quite good and the method is compatible with the synthesis of monoalkenes as well as dienes and trienes. 

Connect the two THP pieces by (a) Julia-Lythgoe olefin synthesis followed by (b) intramolecular Stille coupling. 

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