Allenyl sulfoxide

Note 2. Traces of unreacted triethylamine might cause partial isomerization of the allenyl sulfoxide into the propargyl sulfoxide. The methyl iodide is added to ensure that no triethylamine remains. 

The synthetic utility of the remarkably facile and efficient [2,3]-sigmatropic rearrangement of propargylic sulfenates has been further demonstrated in a variety of preparations and interesting reactions of allenyl sulfoxides , including the preparation of vinylallenes " which are useful intermediates in organic synthesis in general and natural polyenes, such as Vitamins A and D, in particular Two typical examples, taken... 

Nevertheless, new examples have also been reported of allenyl sulfoxides [101] and especially allenyl trichloromethyl sulfoxides [39, Y+-X = S(0)CC13] [102]. There have been many trials to use these sigmatropic rearrangements for the synthesis of diallenes (compare 40 — 42), e.g. the reaction of the diols 43 with trichloromethane-sulfenyl chloride 44 to the diallenes 45 (Scheme 7.7) [103]. 

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

Sulfur-containing allenes can be subdivided into donor-functionalized allenes such as allenyl thioethers and into acceptor-functionalized allenes such as allenyl sulfoxides and sulfones. In this section only the synthesis and chemistry of donor-substituted sulfur-containing allenes will be summarized. 

The iodohydroxylation of 1,2-allenyl sulfoxide 171 with I2 in the presence of H20 exhibits E-selectivity leading to (E)-2-iodo-3-hydroxy-l-alkenyl sulfoxide [88]. By using Br2, CuBr2 or NBS, (E)-2-bromo-3-hydroxy-l-alkenyl sulfoxide is produced. For the chlorohydroxylation of a sulfoxide, CuCl2 and silica gel were used to mix with the sulfoxide to deliver the (E)-chlorohydroxylation products highly stereoselec-tively [88]. The chirality in the allene moiety can be efficiently transferred to the final allylic alcohols. Under the catalysis of a Pd or Ni complex, the C-X and C-S bonds can be coupled to introduce different substituent(s) into the different locations of the C=C bond. 

The reaction of 1,2-allenyl sulfoxides with sodium malonate also afforded 2-[bis (methoxycarbonyl)methyl]-2-alkenyl sulfoxides 177, which upon further transformation would provide an efficient access to butenolide derivatives 180 [90, 91]. 

Diethylamine can readily undergo nucleophilic addition with 1,2-allenyl sulfoxides to afford 2-diethylamino-2-enyl sulfoxides 181, which can be easily converted to a-hydroxy ketones 182 or /3-keto sulfoxides 183 [94]. 

The cycloaddition of allenyl sulfoxide 135 and cydopentadiene occurred at room temperature, giving the single adduct 136. The initially formed allylic sulfoxide underwent a rapid [2,3]-sigmatropic rearrangement. Treatment of 136 with trimethyl phosphite furnished alcohol 137. It should be noted that the reaction of methyl 4-hydroxy-2-butynoate with cydopentadiene failed to give 137. Thus, the allene 135 is considered as a masked and more reactive alkyne equivalent. 

The cycloaddition of allenes carrying an electron-withdrawing phosphorus substituent has also been studied [118]. Allenyl phosphine oxide 138 is prepared in a manner analogous to allenyl sulfoxide. The [4+ 2]-cycloaddition reaction of 138 with cyclopentadiene proceeded with a high endo selectivity. 

Scheme 20.29 Synthesis and cyclization of an enyne-allenyl sulfoxide.

Gedanken and colleagues136 investigated the Diels-Alder reactions of trichloromethyl allenyl sulfoxides 203 and cyclopentadiene under ultrasound irradiation. Allenes 203 are generally very sluggish in reactivity. However, when ultrasound was applied, the reactions of allenes 203 with cyclopentadiene were completed within 2 hours (equation 57). Mixtures of endo (204) and exo (205) isomers were obtained in all instances. When the y-position of the allenyl sulfoxides was substituted, additional mixtures of E and Z isomers were obtained. 

Generation of a-sulfinyl carbanions can also occur in 1 -alkenyl sulfoxides and can be easily achieved by using such bases as lithium diisopropylamide30 32, /erf-butyllithium33 and butyl-lithium (for allenyl sulfoxides)34. 

Allenyl sulfoxides are readily metalated at the a-position with butyllithium to give the corresponding a-lithio-derivatives which react with various electrophiles34. 

Vinyl sulfoxides have been used as synthetic equivalents of alkynes in reactions with diazoalkanes to prepare pyrazoles. The initially obtained adducts subsequently eliminate or rearrange the sulfoxide moiety to achieve pyrazoles lacking the sulfur function. Thus, the adducts resulting by reaction of CH2N2 with the sulfinylated double bond of allenyl sulfoxides 213 are transformed through a sulfoxide-sulfenate rearrangement into hydroxymethyl pyrazoles 214 [168], whereas those obtained by reaction with sulfinyl coumarins 215 suffered sulfinyl elimination into the pyrazoles 216 [169]. In both cases l,H-pyrazoles were obtained as a consequence of a final tautomerization step (Scheme 101). These studies were carried out on racemic sulfoxides. 

Allenyl sulfoxides and sulfones offer an efficient entry to dihydrofurans and other oxacycles via the base-catalyzed cyclization with a tethered hydroxy group (Equation 46) <20010L3385>. 

In the case of steroidal propargylic alcohols the first rearrangement produced a mixture of allenyl sulfoxides, epimeric at the sulfur atom, which reacted with an added nucleophile to produce substituted allylic sulfoxides. Rearrangement of the sulfoxide resulted in the exclusive formation of a-hydroxy derivatives. This reaction sequence has been applied in a synthesis of hydrocortisone acetate74 (Nu = OCH3) from androstene-3,17-dione and in a transformation of mesantrol75 (Nu = malonate) to a spirolactone. 

The first [2,3] sigmatropic rearrangement of a propargylic sulfenatc to an allenyl sulfoxide 14 was observed during the attempted preparation of l-phenyl-2-propynyl trichloromethanesulfe-nate (13) by reaction of trichloromethanesulfenyl chloride with l-phenyl-2-propynol108. 

A high degree of stereoselectivity is also observed in the reaction of 17a-ethynyl-17/ -hydroxy-4,9(1 l)-androstadien-3-one with phenylsulfenyl chloride, which affords a single diastereomer of the steroidal allenyl sulfoxide 18110. 

The addition of an allyl alcohol to racemic allenyl sulfoxides results in vinyl ethers with the sulfinyl moiety at C-1 that undergo sigmatropic rearrangements upon distillation to produce 2,4-dienones after ehmination of sulfenic acid. In one example, an isomeric vinyl ether was obtained with a sulfinyl methyl substituent at C-2 that gave rise to a sulfinyl enone upon rearrangement [138]. In related work, the addition-elimination of an allyl alkoxide to a functionalized vinyl sulfoxide results in a sulfinyl enol ether that rearranges with loss of sulfenic acid to the unsaturated ester [139-141] (Scheme 21). 

The role of allylic sulfoxides as homoaldol equivalents in the synthesis of ( )-allylic alcohols was summarized earlier. A more recent finding is that allylic sulfoxides are precursors for conjugated dienes (equation 70). The elimination is regioselective but stereorandom. The 2,3-rearrangement of propar-gylic sulfenates gives allenyl sulfoxides. Allenyl sulfoxides are valuable synthetic intermediates. They can be converted into stereochemically homogeneous allenes, e.g. (205 equation 71). ... 

Altenbach used the Michael addition of sodium methyl malonate to allene (206) for a dia-stereoselective spiroannulation to a steroid (equation 72). Or, in imaginative work by Okamura, allenyl sulfoxides were transformed into enantiomerically pure hydrocarbons by pericyclic reactions like electrocyclic ring closure (equation 73) or intramolecular cycloaddition (equation 74). Note that the starting materials (propargylic alcohols) are readily accessible as single enantiomers. 

A range of diverse substituted allyl phenyl sulfoxides, which are available by addition of dimethyl cuprate to allenyl sulfoxides or more generally by alkylation of simpler analogs, - have been converted into allylic alcohols possessing predominantly ( )-stereochemistry (E Z 90 10) following simple admixture with trimethyl phosphite - or thiophenolate (MeOH, 60 C, 7 h Scheme 98 Scheme 99 for a lower selectivity see Scheme 98, entry a). ... 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

An allenyl sulfoxide containing triene underwent low-temperature IMDA reaction in situ to give a single product as a 60 40 mixture of diastereoiners at the asymmetric sulfur atom19. The intermediate was used as an intermediate in the synthesis of the fungal metabolite (+)-stcr-purene. 

Chloroallyl sulfoxides. Allenyl sulfoxides undergo addition of HCl in the presence of AICI3-H2O. 

Indolylmethyl phenyl sulfoxides. a-Ethynyl-o-acetamidobenzyl alcohols undergo 0-sulfenylation, which is immediately followed by a [2,3]sigmatropic rearrangement. The ensuing allenyl sulfoxides are prone to cyclize. 

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