Stereoselective Alkene Synthesis

Fig. 16.20. Alkenylation of isomeric alkenylboronic acid esters with isomeric iodo-alkenes stereoselective synthesis of isomeric 1,3-dienes.

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

Of greater potential practical significance, however, are the note193 and full papers194,195 in which Fabre, Julia and Verpeaux describe a new stereoselective synthesis of trisubstituted alkenes in which vinyl sulphones are attacked by Grignard reagents in the presence of iron or nickel catalysts (equations 82-84). 

Bis-pyranoside alkenes are reported as novel templates for the stereoselective synthesis of highly substituted, adjacently linked tetrahydrofurans <96TL3619>. 

A number of procedures for stereoselective synthesis of alkenes involving alkenylboranes have been developed. For each of the reactions given below, show the structure of the intermediates and outline the mechanism in sufficient detail to account for the observed stereoselectivity. 

Both E- and Z-isomers of the terpene y-bisabolene have been isolated from natural sources. The synthesis of these compounds can be achieved by stereoselective alkene syntheses using borane intermediates. An outline of each synthesis is given below. Indicate the reaction conditions that would permit the stereoselective synthesis of each isomer. 

STEREOSELECTIVE SYNTHESIS OF 2,2-DISUBSTITUTED 1-FLUORO-ALKENES (E)-[lFLUORO(2-PHENYLCYCLOHEXYLlDENE)-... 

N.G. Bandur, K. Harms, U. Koert, First stereoselective synthesis ofa Pro-Pro -alkene dipeptide isostere, Synlett (2005) 773-776. 

A. Otaka, F. Katagiri, T. Kinoshita, Y. Odagaki, S. Oishi, H. Tamamura, N. Hamanaka, N. Fujii, Regio- and stereoselective synthesis of ( )-Alkene frans-Xaa-Pro dipeptide mimetics utilizing organocopper-mediated Anti-S M2 reactions, J. Org. Chem. 

Y. Sasaki, A. Niida, T. Tsuji, A. Shigenaga, N. Fujii, A. Otaka, Stereoselective synthesis of (Z)-alkene-containing proline dipeptide mimetics, J. Org. Chem. 71 (2006) 4969 979. 

X.J. Wang, S.A. Hart, B. Xu, M.D. Mason, J.R. Goodell, F.A. Etzkorn, Serine-c/s-proline and Serine-frans-proline isosteres Stereoselective synthesis of (Z)- and ( )-alkene mimics by still-wittig and ireland-claisen rearrangements, J. Org. Chem. 

C.Y. Cheng, B.l. Liou, S.T. Jih, Stereoselective synthesis of frans-( )-A/- 2-[4-(3,4-dichlorophenyl)but-2-en-2-yl]cyclohexyl pyrrolidine as an alkene mimetic of the aryla-cetamide analgesics, J. Chinese Chem. Soc. (Taipei, Taiw/an) 40 (1993) 67-71. 

An efficient stereoselective synthesis of the (pyrrolidin-2-ylidene)glycinate intermediate 325 was reported in a total synthesis of carzinophilin (326), employing an intramolecular cycloaddition of an azide with an alkene (63) (Scheme 9.63). The arabinose derivative 319 was converted into the required azide 321 via the triflate 320. Thermolysis of the azide 321 at 50 °C in THF produced the unstable triazoline 322, which on rearrangement gave the (pyrrolidin-2-ylidene)glycinate 325 in 60-72% overall yield from the triflate 320. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

Highly enantioenriched 4-alken-l-yn-3-ol moieties present in many bioactive acetylenic metabolites from sponges have been efficiently obtained by reduction of the parent 1-trimethylsilyI-4-alken-l-yn-3-one 18 with Alpine-borane or with BH3-SMe2 in the presence of chiral oxazaborolidines, followed by desilylation of the resulting alcohol. This strategy has been applied to the first stereoselective synthesis of petrofuran 19 <99SL429>. 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

Trisubstituted alkenes.9 A stereoselective synthesis of trisubstituted alkenes uses (E)-alkenyl sulfoxides (1)>U as the starting material. These are reduced to the corresponding sulfides (2)," which undergo coupling with Grignard reagents in the presence of complexes of nickel chloride and phosphines as catalyst.12 The products (3) are obtained in steroisomeric purity of > 99%. 

Use of a-oxoketene dithioacetals and organocuprates provided a stereoselective synthesis of tri- and tetra-substituted alkenes.109 In fact, it was reported that either the (E)- or (Z)-alkene could be prepared by the proper choice of cuprate and of the sequence of addition (Scheme 21). 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

The [2+1] cycloaddition between metal carbenoid intermediates and alkenes is a very powerful method for the stereoselective synthesis of cyclopropanes [1-3]. Indeed, the vast majority of chiral catalysts developed for carbenoid chemistry were specifically designed for asymmetric cyclopropanation [1-3]. In recent years, however, a number of other enantioselective cydoadditions have been reported. 

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