Enantioselective Carbometalation of Cinnamyl Derivatives: New Access to Chiral Disubstituted Cyclopropanes— Configurational Stability of Benzylic Organozinc Halides

Norsikian, Stéphanie; Marek, Ilan; Klein, Sophie; Poisson, Jean‐François; Normant, Jean F.

doi:10.1002/(sici)1521-3765(19990702)5:7<2055::aid-chem2055>3.0.co;2-9

Cited by 133 publications

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“…Thus, reaction of the homopropargyllithium reagent 177 with (E)-b-methylstyrene 178 in diethyl ether/THF, followed by protonation, produced the cyclized adduct 179 in 50 % yield as a single diastereomer with a trans-relationship between the substituents on the carbocycle (Scheme 7-107) [130]. The high diastereoselectivity observed for the reaction between benzylic organolithium derivatives and electrophiles has been addressed for cinnamyl alcohols [131] as well as for secondary and tertiary cinnamyl amines [132]. However, the diastereoselectivity in the carbolithiation of cinnamylmethylether with either tBuLi, benzyllithium or alkyllithium was only recently investigated and found to be quite good, as proved by the products obtained upon subsequent treatment with three different electrophiles [133], confirming earlier results [132].…”

Section: Carbometallation Reactions Of Alkenesmentioning

confidence: 99%

“…The high diastereoselectivity observed for the reaction between benzylic organolithium derivatives and electrophiles has been addressed for cinnamyl alcohols [131] as well as for secondary and tertiary cinnamyl amines [132]. However, the diastereoselectivity in the carbolithiation of cinnamylmethylether with either tBuLi, benzyllithium or alkyllithium was only recently investigated and found to be quite good, as proved by the products obtained upon subsequent treatment with three different electrophiles [133], confirming earlier results [132]. The selectivity in the addition of tBuLi to a-methylcinnamyl methyl ether 180 was examined using the conditions developed for the carbolithiation of primary cinnamyl ethers (Scheme 7-108).…”

Section: Carbometallation Reactions Of Alkenesmentioning

confidence: 99%

“…Scheme 7-108 Selective addition of tBuLi to a-methylcinnamyl methyl ether [132,133]. Scheme 7-112 Diastereoselective carbolithiation of a chiral lithium alkoxyamide [136].…”

Section: 182mentioning

confidence: 99%

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Carbometallation Reactions

Marek¹,

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Banon-Tenne³

2004

Metal‐Catalyzed Cross‐Coupling Reactions

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Section: Carbometallation Reactions Of Alkenesmentioning

confidence: 99%

Section: Carbometallation Reactions Of Alkenesmentioning

confidence: 99%

See 1 more Smart Citation

Carbometallation Reactions

Marek¹,

and²,

Banon-Tenne³

2004

Metal‐Catalyzed Cross‐Coupling Reactions

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“…Electrophilic substitutions at carbon, for example the reaction of an organometallic reagent with an electrophile, can occur either with retention [236,238,274,275,525,529] or inversion [234,471] at the nucleophilic carbon atom [57,189,522,531,532].…”

Section: 48mentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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“…4 1,2-Disubstituted alkyl chains possessing sp 3 stereocenters could theoretically also be obtained through the carbometalation of appropriate alkenes (Scheme 1, path c). 5 However, these transformations are much more challenging than the carbometalation reactions of alkynes, since the carbometalated product is usually of similar reactivity to the starting organometallic species and an oligomerization reaction typically occurs. 6 Moreover, when the reaction is performed on the α,β-disubstituted double bond, several issues, such as: (1) regio- and stereoselectivity of the addition; (2) configurational stability of the resulting sp 3 organometallic species; and (3) diastereoselectivity of the reaction with electrophiles; are of major concern.…”

Section: Introductionmentioning

confidence: 99%