Conjunctive reagent

Oompound 1, 2-(hydroxymethyl )a11y1trimethylsilane, represents a conjunctive reagent which can be considered as the equivalent of zwitterion 2, possessing a nucleophilic allyl anion synthon and an electrophilic allyl... 

The presence of the catalyst can also favor multiple Diels-Alder reactions of cycloalkenones. Two typical examples are reported in Schemes 3.6 and 3.7. When (E)-l-methoxy-1,3-butadiene (14) interacted with 2-cyclohexenone in the presence of Yb(fod)3 catalyst, a multiple Diels-Alder reaction occurred [21] and afforded a 1 1.5 mixture of the two tricyclic ketones 15 and 16 (Scheme 3.6). The sequence of events leading to the products includes the elimination of methanol from the primary cycloadduct to afford a bicyclic dienone that underwent a second cycloaddition. Similarly, 4-acetoxy-2-cyclopenten-l-one (17) (Scheme 3.7) has been shown to behave as a conjunctive reagent for a one-pot multiple Diels-Alder reaction with a variety of dienes under AICI3 catalysis, providing a mild and convenient methodology to synthesize hydrofluorenones [22]. The role of the Lewis acid is crucial to facilitate the elimination of acetic acid from the cycloadducts. The results of the reaction of 17 with diene... 

A slight modification of the cyclopropyl conjunctive reagent transforms a cyclopentannulation into a cycloheptannulation. Thus, the 2-vinylcyclopropyllithium reagent 3, converted to its cuprate 4, generates a 1,2-divinylcyclopropane. Heating to only 180 °C leads to smooth Cope type rearrangement, driven by the release of the cyclopropyl strain, to create a perhydroazulene ring systerh of many sesquiterpenoids (Eq. 19) 20>. 

To direct a solvolytic ring opening, 2-methoxycyclopropyllithium (6) was developed as a chain extension conjunctive reagent. The failure of P-elimination to occur in 6 presumably derives from the high strain of cyclopropene and poor orbital overlap for elimination. The aldehyde adducts smoothly solvolyze to give p,Y unsaturated aldehydes (Eq. 22) 23) which are best initially isolated as their hemithioacetals. 

It is obvious that the number of potentially useful conjunctive reagents has barely been touched. For the three discussed herein, the synthetic transformations developed... 

The carbons dotted in the product derive from the cyclopropyl conjunctive reagent. 

Electrophilic Cyclopropyl Heteroatom Substituted Conjunctive Reagents... 

Inverting the electronic sense of the small ring conjunctive reagent expands the range of substrates that would be suitable reaction partners. The aldehydes 37a 88> and 38 89) are available by the formylation of the corresponding lithium salt with DMF. 

These electrophilic conjunctive reagents require donor reactants. The cyclopropyl-carbinols as precursors to cyclobutanones arise by simple addition of organometallics. For example, the cyclobutanone 47 derives by addition of vinyllithium to 44 followed by rearrangement with aqueous fluoroboric acid 92). In some cases, this route to cyclopropylcarbinols is preferred. Addition of 41 to aldehydes or ketones... 

Olefination reactions converts these electrophilic conjunctive reagents into vinyl-cyclopropanes (Eq. 55-58) 89 9U93). While in the simple aldehydes, the normal... 

This sequence initiated by the nucleophilic cyclopropyl conjunctive reagent 9 allows facile annulation concommitant with regiocontrolled further structural elaboration as outlined in Eq. 8429). With the electrophilic conjunctive cyclopropyl reagent 58, this [3 + 2] annulation onto a vinyl organometallic (Eq. 85) has the availability of the... 

The silicon analogue 74 u5) also appears to be a potentially useful conjunctive reagent in this sequence even though silicon appears to retard the rearrangement71 It is generated by silylation of 37a followed by reductive lithiation (Eq. 90). The... 

An alternative strategy to these same structural units takes advantage of the use of the electrophilic conjunctive reagent 37b which converts ketones to a-vinylcyclobuta-nones such as 95 and % in Eqs. 112 and 113 respectively. Addition of a nucleophile... 

The utility of small ring conjunctive reagents in total syntheses appears to be very great. The convulated structural correlations between the target and a starting material hamper its ready adaptation. The facility and stereochemical implications make the rethinking of retrosynthetie analysis well worth the effort. To illustrate some of this potential, several applications in the total synthesis of natural and unnatural products are analyzed. 

The construction of cyclopentanones can take several avenues based upon the concepts evolving from use of small ring conjunctive reagents. A very simple one is a-cuparenone (183) which can be thought to derive by a ring expansion of a cyclobutyl carbinyl system as in 184 (Scheme 8) 110,1U). If X. is an anion stabilizing... 

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

The unique reactivity pattern of alkynyl iodonium salts discussed in Sections II,A.2 and II,D,la can also serve as two-carbon conjunctive reagents in the synthesis of pyrroles, dihydropyrroles, and indoles. Feldman et al. found that combination of alkyl or aralkyl tosylamide anions 101 with phenyl(propynyl)iodonium triflate (102) furnishes the corresponding dihydropyrroles 103 (95JOC7722) (Scheme 28). 

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