Four-membered rings, heterocycle synthesis

The coordination of the phosphine P(ft-Pr)2Ph to the Lewis acidic Ga center is essential for the synthesis of both compounds. In the absence of any Lewis base, the most likely reaction product would be the heterocubane [ClGaSbSi(/-Pr)3]4. However, in analogy to the results observed for reactions of heterocycles [R MER with Lewis bases, leading to base-stabilized monomeric compounds, both the formation of 84 and 85 can be explained by reaction of such a heterocubane intermediate with the phosphine base. According to the description of heterocycles as head-to-tail adducts, heterocubanes may be described as Lewis acid-base adducts between two four-membered rings as shown in Fig. 45. 

The key step in Biichi s total synthesis of loganin (5i)23 made use of the expansion of a four-membered ring to an oxygen-containing heterocycle by retro-aldol reaction. This strategy was later exploited by Tietze in his total synthesis of hydroxyloganin (54) as well as hydroxyloganic acid (55) 24). 

Although four-membered rings are highly strained and not very stable heterocycles, there are some examples (Fig. 3.5) for the preparation of heterocycles of this type on solid supports. Different /9-lactams (229-230) have been synthesized employing different synthetic pathways [133, 275, 306-309] such as the addition of ketenes (Scheme 3.34) [306], or ester enolates to imines [133]. Also the synthesis of four-membered rings with two heteroatoms has been reported [310]. 

A fascinating feature of the chemistry of boron-phosphorus heterocycles is the existence of stable singlet biradicals, e.g. fBuBP Pr2)2 (for a discussion of the electronic structure, see Section 5.4.2.2). The synthesis of this four-membered ring is illustrated in Scheme 5.2. Related derivatives of the type (RBPR 2)2 are also prepared by a salt-elimination reaction of the appropriate lithium phosphide with a 1,2-dichlorodiborane or, in the case of the perphenylated derivative (PhBPPh2)2, by reduction of the cyclic dimer [Ph(Cl)BPPh2]2 with lithium naphthalenide (Scheme 9.11). ... 

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the fnms-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the [2+2]-cycloreversion start. It leads to triphenylphosphine oxide and an acceptor-substituted fnms-configured olefin. This frara-selectivity can be used, for example, in the C2 extension of aldehydes to /ran.v-con figured aj8-unsaturated esters (Figure 9.11) or in the fnms-selective synthesis of polyenes such as /1-carotene (Figure 9.12). 

VIII. HETEROCYCLIC SYNTHESIS A. Four-membered Rings... 

This has met with success in a number of areas related to the low temperature observation of the parent species itself, the synthesis of relatively stable substituted derivatives, and heterocyclic and annelated analogs, e.g., benzocyclobutadiene and biphenylene derivatives. These cyclobutadienoids , each class of which is of significant importance in its own right, have interesting physical and chemical characteristics due to incorporation of a potentially delocalized, antiaromatic four-membered ring. Recent progress in this area will be the topic of this report. 

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