Cyclopropanes stereoselective synthesis

S. Arai, K. Nakayama, K. Hatano, T. Shioiri, Stereoselective Synthesis of Cyclopropane Rings under Phase-Transfer-Catalyzed Conditions , J. Org Chem. 1998, 63, 9572-9575. 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

Particularly interesting applications of isopropylidenediphenylsulfuran [459, 464] have been reported. Improvements in its preparation and use led [465] to a claimed industrially viable stereoselective synthesis of Deltamethrin, the most potent commercially available insecticide, as well as to other stereoselective syntheses of cyclopropane derivatives [466]. 

Where there is an electron-rich olefinic double bond in the diazoketone as in the 2-substituted 3,4-dihydropyran derivative 47, the intramolecular cyclopropanation produces oxatricyclic ketones, e.g. 48 (equation 57)86 87. Rhodium(II) acetate is the catalyst of choice for this transformation. An interesting application of this method is found in a stereoselective synthesis of ( )-/ -chamigrene 49 (equation 5S)88. 

Stereoselective synthesis of medium-sized rings was possible from compounds such as (77 Scheme 15),l0la which were readily derived from intramolecular cyclopropanations (see equation 18). Treatment of (77) with 1 equiv. of ethanethiol in the presence of a catalytic amount of zinc chloride generated the hemithioacetal (78), which in the presence of boron trifluoride etherate formed the cycloheptane system (79), in which the two carbonyls are differentiated. 

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. 

Acyclic pentadienyliron complexes show a similar reactivity towards nucleophiles but have found less application so far. Donaldson and coworkers reported an interesting cyclopropanation starting from a pentadienyliron complex (Scheme 1.31) [69]. This procedure has beenused for the stereoselective synthesis of cyclopropylglydnes [70], the preparation of the C9—C16 alkenylcyclopropane segment of ambrutidn [71] and the synthesis of hydrazulenes via divinylcydopropanes [72],... 

K. Stereoselective synthesis of cyclopropanes via homoallylic participation. Bull. Chem. Soc. Jpn. 1996, 69, 31-39. 

If the olefin is chiral (entries 23-25) high diastereoselectivity has been observed, when the center of asymmetry is at C-3 of cyclic silyl enol ethers (entry 24). Cyclopropanation then occurs trans to the substituent at this carbon 57) exclusively, and due to the very mild cleavage conditions this mww-relationship is preserved in the subsequent ring opening (vide infra). This protocol has been applied to introduce a side chain during the stereoselective synthesis of a prostaglandin58> and of dicranenone A 59). 

Scheme 24). A Li/SeMe exchange must be involved in the intermediate cycloal-kylmethyllithium to explain the cyclopropane ring formation. This lithium me-thaneselenolate displacement has been extended to the stereoselective synthesis of functionalized arylcyclopropanes by reaction with olefinic substrates [30] (Scheme 25). 

A discussion of approaches to the stereoselective synthesis of 3-(dichlorovinyl)-2,2-dirrethylcyclapraparie carboxylic acid through intramolecular alkylation of an enolate ion is presented. Principles for achieving good control of the relative stereochemistry about the cyclopropane ring will be described. The control of the absolute stereochemistry on the ring was accomplished through the use of a chiral enolate. 

We chose to explore the intramolecular alkylation of amide enolates as a potential stereoselective route to cis pyrethroid cyclopropane carboxylates. If the relationship between the stereoselection in enolate formation and ring closure is operable, amide enolates would be an excellent means of developing a stereoselective synthesis of cis products (8). Furthermore, recent progress in achieving enantioselection in the intermolecular alkylation of chiral amide enolates would provide a means of obtaining optically active pyrethroid acids (Figure 6) (9-13). 

Normally the chiral auxiliaries are introduced and removed in the asymmetric synthesis of Simmons-Smith reactions of allylic alcohols to provide mostly /rani-disubstituted cyclopropanes. Stereoselective syntheses of c -disubstituted cyclopropanes are difficult to achieve. Starting from (Z)-3-phenylprop-2-en-l-ol (80a) and (Z)-6-phenylhex-2-en-l-ol (80b), the corresponding c -disubstituted cyclopropanes 81a and 81b were prepared by first treating them with diethylzinc followed by diethyl (- -)-(/ ,7 )-tartrate (DET). A zinc-bridged intermediate is assumed to be formed first. This is subsequently treated with diethylzine and diiodomethane to give the products 81. The reaction conducted at — 12 "C gave the cyclopropanated products 81a and 81b with 70 and 81% ee, respectively.This method has the advantages that the introduction of the chiral auxiliary to the substrate and its removal are not neccessary and that both cis- and trans-disubstituted cyclopropanes could be prepared from (Z)- and ( )-allylic alcohols, repectively. 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

This method was used in the stereoselective synthesis of cis- and /ran -hemicaronic aldehydes 9 which were prepared in high enantiomeric purity starting from optically active sorbic aldehyde diene tricarbonyliron complex 6 via Wittig olefination, diazo ester cyclopropanation (copper powder), and further conversion with release of the cyclopropane from the complex and ozonolysis. ... 

Yokomatsu, T., Yamagishi, T., Suemune, K., Abe, H., Kihara, T., Soeda, S., Shimeno, H., and Shibuya, S., Stereoselective reduction of cyclopropylalkanones possessing a difluoromethylenephosphonate group at the ring. Application to stereoselective synthesis of novel cyclopropane nucleotide analogues. Tetrahedron, 56, 7099, 2000. 

Stereoselective synthesis of cydopropane-1,2-dicarboxylic acids or 1,2-dicyano substituted cyclopropanes by Michael addition (see also Hassner - Ghera - Little). 

In order to facilitate the search for the stereoselective synthesis of a cyclopropane derivative with a particular substitution pattern, this section is organized according to the carbene (carbenoid) substituents. The sequence of carbenes therefore parallels that in the Houben-Weyl Volume E 19 b on Carbene (Carbenoidc)/Carbine which deals with all aspects of carbene chemistry including scope and limitations of various [2 + 1] cycloadditions. For many classes of carbenes. and. in particular, for typical experimental procedures, cross references are made to the corresponding pages in that volume. 

The zinc-based Simmons-Smith type procedures frequently require rather harsh conditions in order to provide acceptable cyclopropane yields. Also, the discrimination between allylic alcohols, homoallylic alcohols and olefins without a hydroxyl group is often not very pronounced. These drawbacks are avoided by a new method which substitutes samarium metal (or samarium amalgam) for zinc (Table 4)43. This cnahlcs only allylic alcohols to be cyclo-propanated under very mild conditions, even for highly crowded substrates. The hydroxy-directed diastereofacial selectivity is good to excellent for cyclic olefins. Due to this property, the method has been applied to the stereoselective synthesis of 1,25-dihydroxycholecalciferol44. 

A convenient and novel one-pot organocatalytic methodology for the stereoselective synthesis of highly functionalized nitrocyclopropenes has been developed [90] (Table 3.9). DBU (1) catalyses the addition of dimethyl chloromalonate to a variety of nitroolefins to afford a Michael adduct, which cyclizes to form the cyclopropane in the presence of 1 under carefully controlled reaction conditions with outstanding diastereoselectivity. 

A novel Wittig reaction of cyclohexenones using vinylphosphonium ylides leads to the construction of the cyclopropane ring and this has found application in the stereoselective synthesis of trachyloban-19-oic acid. A further synthesis of gibberone has been reported.The sesquiterpenoid santonin formed the starting material for syntheses of pachydictyol and dictyolene. ... 

The cyclopropane ring is a common structural motif found in pyrethriods, the antidepressant tranylcyclopromine, papin and cystein protease inhibitors, potential antipsychotic agents, and anti-HIV compounds. Thus, considerable attention has been paid to the stereoselective synthesis of cyclopropane-containing compounds. The use of rhodium in cyclopropanation was made popular by contributions from Doyle and Davies. They have focused, over the years, on using chiral Rh(II) catalysts for asymmetric cyclopropanation via the decomposition of diazo compounds in the presence of olefins. Examples of the Rh(II)-... 

In 2009, Lambert reported a mild, efficient, and stereoselective synthesis of fused cyclopentenes via Mgl2-promoted isomerization of activated VCPs. The VCPs were prepared by Pd-catalyzed cyclopropanation of 1,3-dienyl p-ketoesters in moderate to high yields and good diastereoselectivities. Typical standard reaction conditions for the VCP-CP rearrangement (i.e., pyrolysis, transition metal catalysis, standard Lewis acid catalysis) were found to be ineffective for these substrates. However, the use of 1.5 equiv. of Mgl2 led to conplete conversion, providing bicyclic cyclopentenes in high yields fScheme 11.15L... 

F.-Y. Wu, Y. Li, H. Feng, Q. Wu, B. Jiang, F. Shi, S.-J. Tu, Synthesis 2011, 2459-2465. Stereoselective synthesis of functionalized cyclopropane derivatives via a-thiocyanate ketone-based three-component reaction. 

A modified Simmons-Smith reaction has been used in the stereoselective synthesis of a naturally occurring substance called U-106305 containing six cyclopropane rings. In the synthesis, four of the six rings arise by Simmons-Smith-type cyclopropanation. The red lines in the structural formula identify the bonds to the CH2 groups that are introduced in this way the blue lines identify bonds that originated with the iiutial reactant. 

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