Bromides vinyl substitutions

Saito has recently reported high yields and enantioselectivities in aziridine synthesis through reactions between aryl- or vinyl-substituted N-sulfonyl imines and aryl bromides in the presence of base and mediated by a chiral sulfide 122 (Scheme 1.41) [66]. Aryl substituents with electron-withdrawing and -donating groups gave modest transxis selectivities (around 3 1) with high enantioselectiv-... 

Monomers which can add to their own radicals are capable of copolymerizing with SO2 to give products of variable composition. These include styrene and ring-substituted styrenes (but not a-methylstyrene), vinyl acetate, vinyl bromide, vinyl chloride, and vinyl floride, acrylamide (but not N-substituted acrylamides) and allyl esters. Methyl methacrylate, acrylic acid, acrylates, and acrylonitrile do not copolymerize and in fact can be homopolymer-ized in SO2 as solvent. Dienes such as butadiene and 2-chloro-butadiene do copolymerize, and we will be concerned with the latter cortpound in this discussion. 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

Table II. Functionalized Vinylic Bromides Useful in the Vinylic Substitution Reaction...

Table III. Vinylic Substitution Productions from 1-Hexene and Various Vinylic Bromides and Morpholine ...

Data from other studies, including the infrared spectroscopy of vinyl-substituted polysilanes (154), copolymerization of some vinylpolysilanes with styrene and with acrylonitrile (154), and kinetics of the reaction of organosilylacetylenes with ethylmagnesium bromide (213), are consistent with the above sequence. 

Like other acid chlorides and cyanogen bromide, vinyl chloroformate brings about fission of benzylic and allylic amines e.g. hydrastine is converted into the enol lactone (145).169 Normorphine and norcodeine give substituted thioureas (146) with alkyl isothiocyanates.170... 

Numerous aryl bromides, iodides [203], borates [204] and triflates [205, 206] have been successfully carbonylated. Triflates could serve as a route for the synthesis of arenecarboxylic acid derivatives from phenols. This carbonylation using dppf in a catalytic mixture generally shows higher efficiency than PPhj or P(o-Tol)3 [207]. Poor performance is also noted for PPhj in a Pd-catalyzed vinyl substitution of aryl bromides [208]. Side-reactions involving the formation of [PPhjAr]Br and ArH are responsible. A system which is catalyzed effectively by PdCljfdppf) under 10 atm CO is the desulfonylation of 1-naphthalenesulfonyl chloride 58 in the presence of Ti(OiPr)4. Formation of isopropyl 1-naphthoate 59 can be explained in a sequence of oxidative addition, SOj extrusion, carbonylation and reductive elimination (Fig. 1-27) [209]. A notable side-product is di-l-naphthyl disulfide. 

Aryl halides which are rather inert in usual organic reactions can undergo reactions by means of palladium catalysts. Thus, styrene and stilbene derivatives are obtained by reaction of olefins with aryl bromides at 125 °C using Pd(0Ac)2 (1 mol%) and tri-(o-tolyl)phosphine (2 mol%)83. The palladium-catalyzed vinylic substitution reaction is applicable to a variety of heterocyclic bromides including pyridine, thiophene, indole, furan, quinoline and isoquinoline84. Thus, reaction of 3-bromopyri-dine with l-(3-butenyl)phthalimide at 100 °C gives l-[4-(3 -pyridyl)-3-butenyl]-phthalimide (yield of mixed amine 57%, selectivity 68%) at 100 °C. This phthalimide is subsequently converted to nornicotine (188) (Scheme 59). The reaction of acrylic... 

AUylic bromination. [1, 79. after citation of ref. 8]. N-Bromosuccinimide reacts with isolapachol (I) in refluxing CCT by vinylic substitution to give (2) N-iodo-succinimide reacts in the same way.83 (8-1 sopropylfurano- 1,4-naphthoquinone (3) was obtained by cyclization of the vinylic bromide (2) with N1S and also by the action of two equivalents of N IS on (1). Even when the unsaturated side chain has a primary or secondary hydrogen in the allylic position, for example (4), the same vinylic substitution was observed (5). 

First, the process may not involve a nucleophilic attack on the vinylic carbon. This fact is well recognized in vinylic substitution (2, 3), and a typical example is the substitution of ( )- and (Z)-(3-halovinyl sulfones (3 and 4 X = Cl or Br) by PhS- and MeO- in MeOH (4-6). Both reactions of both substrates are of a second order and give retention of configuration, and the element effects kBJka are 2.3 (E) and 2.2 (Z) with PhS- and 0.84 (E) with MeO-, values that are consistent with rate-determining nucleophilic attack on the vinylic carbon (2). However, for the Z isomer, kBJka with MeO- is 185, and because a-hydrogen exchange is rapid under the substitution conditions, the reaction of the Z-bromide probably proceeds via elimina-... 

Table IV compares the reactivity ratios of a soft (PhS-) to a hard (MeO-) nucleophile in vinylic substitution. PhS is always more reactive, and ratios lower than unity, as for 4, X = Br (4), are certainly due to elimination-addition with MeO . The ratios change by >2000-fold and are sensitive to the geometry of the substrate. An important feature is that for (3-halo-p-nitrostyrenes the ratio decreases strongly with the increased hardness of the (3-halogen (38). The lowest ratios are for the (3-fluoro derivative, whereas the differences between the chloro and bromo compounds are not so large. This behavior is similar to that in SNAr reactions. This behavior can be rationalized by symbiotic effects, which favor the soft-soft PhS--Br interaction and the hard-hard MeO-F interaction. A reactivity-selectivity relationship for vinyl bromides of different electrophilicities does not exist.

Arylation of olefins (6, 156).° The vinylic substitution of aryl bromides with diacetatobis(triphenylphosphine)palladium(II) as catalyst is not satisfactory with bromides containing strongly electron-donating groups (OH, NHa). Two solutions have been reported. One is to use an aryl iodide rather than the bromide and palladium acetate alone as catalyst. 

The other solution is to use tri-o-tolylphosphine in place of triphenylphosphine as the ligand. This variation was used for vinylic substitution reactions with various heterocyclic bromides. An example is the synthesis of nornicotine (1). 

We first synthesized suitably functionalized amides in four steps from the corresponding alkenyl bromides (Scheme 11). The allylsilane function was introduced by cross-metathesis between the terminal alkenes and allyltri-methylsilane. Then, the bromide was substituted by an azide and the latter was reduced to the primary amine by the action of LiAlELj. As before, a pep-tidic coupling with vinyl acetic acid led to the desired starting compound with a diastereomeric ratio /Z=70/30. 

The copper-promoted oxidative addition process reported by Merck [183] on the vinylic bromides 321 gave rise, unexpectedly, to rearranged isopenem products, whose correct structures were independently determined at Sankyo s [184] and Schering s [117]. The S-C4 cleavage promoted by the reaction conditions was not the sole cause of insuccess, since carbacephems, but not carbapenems, could be synthesized by this route [185]. Similarly, intramolecular vinylic substitution of enol mesylate or phosphate 322a, b by the azetidinone nitrogen could not be achieved [84b]. 

---