Carbonyl alkenylation

The dual ability of carbonyl, alkenyl, and alkynyl groups to act as radical precursors as well as radical acceptors is of great importance for synthetic applications, since it would diversify the formation of carbon-carbon bonds by radical reactions. Each functional group has unique characteristics, which permit the generation of radicals from multiple bonds or the addition of radicals to multiple bonds in a selective manner. 

The "right half of the sesquiterpene (+)-p-selinene (as drawn below) includes (R)-(+)-limonene as a substructure. Retrosynthetic disconnection to (if)-(+)-limonene leads to the intermediate carbenium ions la and lb via 15-nor-ll-eudesmen-4-one (carbonyl alkenylation) and 15-nor-13-chloro-2-eudesmen-4-one (dehydrogenation, protective masking of the double bond in the side chain). These carbenium ions arise from (if)-9-chloro-p-menth-l-ene and the acylium ion Ic (synthone) originating from 3-butenoic acid as reagent (synthetic equivalent). (i )-/7-Menth-l-en-9-ol, on its part obtained by hydroboration and oxidation of (if)-(-l-)-limonene, turns out to be the precursor of the chloromenthene. 

A variety of electrophiles are employed for carbonyl alkenylation and arylation that proceed through transmetalation from silicon to transition metal catalysts. For example, addition of alkenylsilanes and aryl(trimethoxy)si lanes to aldehydes is catalyzed by copper/DTBM-SEGPHOS, which mediates transmetalation from silicon to copper to give a wide variety of chiral alcohols with high degree of % ee (Scheme 3-144). The enantioselective alkenylation of imines using 2-(hydroxylmethyl)phenyl-substituted propen-2-ylsilane is catalyzed by a rhodium/chiral diene complex. ... 

Finally (d + aV dditions of 1-alkenyl and 1-alkynyl anions to carbonyl groups should be mentioned. Examples are the addition of vinylmagnesium bromide to ketones e.g. in the first step of Torgov s steroid synthesis (I.N. Nazarov, 1957), and the famous alkynylation of... 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Other pseudo-halides are used for carbonylation. Phenyl tluorosulfonate (484) can be carbonylated to give benzoate[337]. Aryl(aryl)iodonium salts[338], aryl(alkenyl)iodonium salts (485)[339], and arylialkynyl)iodonium salts (486)[340] are reactive compounds and undergo carbonylation under mild conditions (room temperature, 1 atm) to give aryl, alkenyl, and alkynyl esters. lodoxybenzene (487) is carbonylated under mild conditions in... 

The o-keto ester 513 is formed from a bulky secondary alcohol using tricy-clohexylphosphine or triarylphosphine, but the selectivity is low[367-369]. Alkenyl bromides are less reactive than aryl halides for double carbonyla-tion[367], a-Keto amides are obtained from aryl and alkenyl bromides, but a-keto esters are not obtained by their carbonylation in alcohol[370]. A mechanism for the double carbonylation was proposed[371,372],... 

Aldehydes can also be prepared by the carbonylation of aryl and alkenyl halides and triflate, and benzyl and allyl chlorides using tin hydride as a hydride source and Pd(PhjP)4 as a catalyst[377]. Hydrosilancs arc used as another hydride source[378]. The arenediazonium tetralluoroborate 515 is converted into a benzaldehyde derivative rapidly in a good yield by using Et ,SiH or PH MS as the hydride source[379]. 

Organotin compounds such as aryl-, alkenyl-, and alkynylstannanes are useful for the ketone synthesis by transmetallation of acylpalladium 529 and reductive elimination of 530 as shown[389-393]. Acetophenone (531) is obtained by the carbonylation of iodobenzene with Me4Sn. Diaryl ketones... 

The reaction of alkenyl iodides or triflates, alkenylstannanes, and CO affords divinyl ketones[397,398]. Thus the capnellene skeleton 538 has been synthesized by the carbonylation of the cyclopentenyl triflate 536 with the alkenyltin 537[392], The macrocyclic divinyl ketone 540 has been prepared in a moderate yield by the carbonylative cyclization of 539[399]. 

The 2-substituted 3-acylindoles 579 are prepared by carbonylative cycliza-tion of the 2-alkynyltrifluoroacetanilides 576 with aryl halides or alkenyl tri-flates. The reaction can be understood by the aminopalladation of the alkyne with the acylpalladium intermediate as shown by 577 to generate 578, followed by reductive elimination to give 579[425]. 

The alkenylzirconium 685, prepared by hydrozirconation of a terminal alkyne with hydrozirconocene chloride, reacts with alkenyl halide to afford the conjugated diene 686(545]. The Zr reagent can be used even in the presence of the carbonyl group in 687, which is sensitive to Al and Mg reagents. 

Table 2.3 shows very obvious parallels with the TMS scale of C shifts. Thus, the shifts (Table 2.3) decrease in size in the sequence nitroso, nitro, imino, amino, following the corresponding behaviour of the shifts of carbonyl, carboxy, alkenyl and alkyl carbon atoms (Table 2.2). 

Allylation of perfluoroalkyl halides with allylsilanes is catalyzed by iron or ruthenium carbonyl complexes [77S] (equation 119) Alkenyl-, allyl-, and alkynyl-stannanes react with perfluoroalkyl iodides 111 the presence ot a palladium complex to give alkenes and alkynes bearing perfluoroalkyl groups [139] (equation 120)... 

The exo selecdvity of the TiCL-TADDOLate-catalyzed 1,3-thpolar cycloadthdon is improved by the tise of sticcinimide instead of oxazoiidinone as attxiliary for the a,fi-imsatitrated carbonyl moiety (Eq. 8.55). A strong bidentate coo rdinadon of the alkenyl moiety to the metal catalyst is impcrtant in these re... 

Table 6. 4-Hydroxy-l-alkenyl Diisopropylcarbamates from 2-Alkenyl Carbamates and Carbonyl Compounds...

Table 7. 4-Hydroxy-l-alkcnyl Diisopropylcarbamates from 2-Alkenyl Diisopropylcarbamates by Ho-moaldol Addition of Carbonyl Compounds to Trichlorotitanates (via Stannanes)...

The carbanions of 1-alkenyl sulphoxides 400 also react with carbonyl compounds to give the corresponding condensation products384 (equation 237). Solladie and Moine have used this type of reaction in their enantiospecific synthesis of the chroman ring of a-tocopherol 401. Addition of the lithio reagent 402 to the aldehyde 403 affords the allylic alcohol 404 in 75% yield as a sole diastereoisomer481 (equation 238). 

In the presence of a base such as l,4-diazabicyclo[2.2.2]octane (DABCO) or tri-alkylphosphines, conjugated carbonyl compounds such as esters and amides add to aldehydes via the a-carbon to give a-alkenyl-P-hydroxy esters or amides. This sequence is called the Baylis-Hillman reaction and a simple example is... 

Finally the new ylides stabilized with sulfinyl but alkoxy carbonyl groups also behave in a more complex manner than for the simple sulfinyl ylide and the loss of both PhjPO and PhjP is observed [131]. Mixtures of products are obtained among which are alkenyl sulfides as major products but also sulfides and thioesters (Scheme 35). 

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